Sample records for acute organophosphate op

  1. Chronic exposure to organophosphate (OP) pesticides and neuropsychological functioning in farm workers: a review.

    PubMed

    Muñoz-Quezada, María Teresa; Lucero, Boris Andrés; Iglesias, Verónica Paz; Muñoz, María Pía; Cornejo, Claudia Alejandra; Achu, Eduardo; Baumert, Brittney; Hanchey, Arianna; Concha, Carlos; Brito, Ana María; Villalobos, Marcos

    2016-01-01

    Previous studies have demonstrated that acute poisoning from exposure to organophosphate (OP) pesticides in agricultural workers causes adverse health effects. However, neuropsychological and cognitive effects of chronic occupational exposure to OP pesticides remain controversial. To identify, evaluate, and systematize existing evidence regarding chronic exposure to OP pesticides and neuropsychological effects in farmworkers. Using the PubMed search engine, a systematic review process was implemented and replicated according to the PRISMA statement. Eligibility criteria included workers over 18 years of age exposed to OP pesticides as well as assessment of neuropsychological and cognitive functioning. Search terms were in English and Spanish languages and included organophosphate and workers. Of the search results, 33 of 1,256 articles meet eligibility criteria. Twenty-four studies found an association between chronic occupational exposure to OP pesticides and low neuropsychological performance in workers. We classified nine of the studies to have study design limitations. Studies indicated occupational exposure to OP pesticides is linked to difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual-spatial functioning, and coordination. Nine studies find no relationship between OP pesticides exposure and neuropsychological performance. Overall, evidence suggests an association between chronic occupational exposure to OP pesticides and neuropsychological effects. However, there is no consensus about the specific cognitive skills affected.

  2. Chronic exposure to organophosphate (OP) pesticides and neuropsychological functioning in farm workers: a review

    PubMed Central

    Lucero, Boris Andrés; Iglesias, Verónica Paz; Muñoz, María Pía; Cornejo, Claudia Alejandra; Achu, Eduardo; Baumert, Brittney; Hanchey, Arianna; Concha, Carlos; Brito, Ana María; Villalobos, Marcos

    2016-01-01

    Background Previous studies have demonstrated that acute poisoning from exposure to organophosphate (OP) pesticides in agricultural workers causes adverse health effects. However, neuropsychological and cognitive effects of chronic occupational exposure to OP pesticides remain controversial. Objective To identify, evaluate, and systematize existing evidence regarding chronic exposure to OP pesticides and neuropsychological effects in farmworkers. Methods Using the PubMed search engine, a systematic review process was implemented and replicated according to the PRISMA statement. Eligibility criteria included workers over 18 years of age exposed to OP pesticides as well as assessment of neuropsychological and cognitive functioning. Search terms were in English and Spanish languages and included organophosphate and workers. Results Of the search results, 33 of 1,256 articles meet eligibility criteria. Twenty-four studies found an association between chronic occupational exposure to OP pesticides and low neuropsychological performance in workers. We classified nine of the studies to have study design limitations. Studies indicated occupational exposure to OP pesticides is linked to difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual–spatial functioning, and coordination. Nine studies find no relationship between OP pesticides exposure and neuropsychological performance. Conclusions Overall, evidence suggests an association between chronic occupational exposure to OP pesticides and neuropsychological effects. However, there is no consensus about the specific cognitive skills affected. PMID:27128815

  3. Increased Risk of Dementia in Patients With Acute Organophosphate and Carbamate Poisoning

    PubMed Central

    Lin, Jiun-Nong; Lin, Cheng-Li; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Kao, Chia-Hung

    2015-01-01

    Abstract Organophosphate (OP) and carbamate (CM) are the most commonly used pesticides against insects. Little is known regarding the relationship between dementia and acute OP and CM poisoning. A nationwide population-based cohort study was conducted from the National Health Insurance Research Database in Taiwan. The incidence and relative risk of dementia were assessed in patients hospitalized for acute OP and CM poisoning from 2000 to 2011. The comparison cohort was matched with the poisoned cohort at a 4:1 ratio based on age, sex, and the year of hospitalization. During the follow-up period, the incidence of dementia was 29.4 per 10,000 person-years in the poisoned group, and represented a 1.98-fold increased risk of dementia compared with the control cohort (95% confidence interval, 1.59–2.47). This study provides evidence on the association between dementia and acute OP and CM poisoning. Regular follow-up of poisoned patients for dementia is suggested. PMID:26200627

  4. Epidemiology of organophosphate pesticide poisoning in Taiwan.

    PubMed

    Lin, Tzeng Jih; Walter, Frank Gardner; Hung, Dong Zong; Tsai, Jin Lian; Hu, Sheng Chuan; Chang, Jung San; Deng, Jou-Fang; Chase, Jung San; Denninghoff, Kurt; Chan, Hon Man

    2008-11-01

    The nationwide epidemiology of organophosphate pesticide (OP) poisoning has never been reported in detail for Taiwan. This study retrospectively reviewed all human OP exposures reported to Taiwan's Poison Control Centers (PCCs) from July 1985 through December 2006. There were 4799 OP exposures. Most OP exposures were acute (98.37%) ingestions (74.50%) of a single OP (80.37%) to attempt suicide (64.72%) in adults (93.25%). Males were the most common gender (64.95%). Most patients (61.97%) received atropine and/or pralidoxime. The mortality rate for all 4799 OP exposures was 12.71%. Exposures to single OPs without co-intoxicants caused 524 deaths; of these, 63.36% were due to dimethyl OPs. Dimethyl OPs cause the majority of deaths in Taiwan.

  5. Mass spectrometric analyses of organophosphate insecticide oxon protein adducts.

    PubMed

    Thompson, Charles M; Prins, John M; George, Kathleen M

    2010-01-01

    Organophosphate (OP) insecticides continue to be used to control insect pests. Acute and chronic exposures to OP insecticides have been documented to cause adverse health effects, but few OP-adducted proteins have been correlated with these illnesses at the molecular level. Our aim was to review the literature covering the current state of the art in mass spectrometry (MS) used to identify OP protein biomarkers. We identified general and specific research reports related to OP insecticides, OP toxicity, OP structure, and protein MS by searching PubMed and Chemical Abstracts for articles published before December 2008. A number of OP-based insecticides share common structural elements that result in predictable OP-protein adducts. The resultant OP-protein adducts show an increase in molecular mass that can be identified by MS and correlated with the OP agent. Customized OP-containing probes have also been used to tag and identify protein targets that can be identified by MS. MS is a useful and emerging tool for the identification of proteins that are modified by activated organophosphate insecticides. MS can characterize the structure of the OP adduct and also the specific amino acid residue that forms the key bond with the OP. Each protein that is modified in a unique way by an OP represents a unique molecular biomarker that with further research can lead to new correlations with exposure.

  6. Mass Spectrometric Analyses of Organophosphate Insecticide Oxon Protein Adducts

    PubMed Central

    Thompson, Charles M.; Prins, John M.; George, Kathleen M.

    2010-01-01

    Objective Organophosphate (OP) insecticides continue to be used to control insect pests. Acute and chronic exposures to OP insecticides have been documented to cause adverse health effects, but few OP-adducted proteins have been correlated with these illnesses at the molecular level. Our aim was to review the literature covering the current state of the art in mass spectrometry (MS) used to identify OP protein biomarkers. Data sources and extraction We identified general and specific research reports related to OP insecticides, OP toxicity, OP structure, and protein MS by searching PubMed and Chemical Abstracts for articles published before December 2008. Data synthesis A number of OP-based insecticides share common structural elements that result in predictable OP–protein adducts. The resultant OP–protein adducts show an increase in molecular mass that can be identified by MS and correlated with the OP agent. Customized OP-containing probes have also been used to tag and identify protein targets that can be identified by MS. Conclusions MS is a useful and emerging tool for the identification of proteins that are modified by activated organophosphate insecticides. MS can characterize the structure of the OP adduct and also the specific amino acid residue that forms the key bond with the OP. Each protein that is modified in a unique way by an OP represents a unique molecular biomarker that with further research can lead to new correlations with exposure. PMID:20056576

  7. Oximes in Acute Organophosphate Pesticide Poisoning: a Systematic Review of Clinical Trials

    PubMed Central

    Eddleston, Michael; Szinicz, Ladislaus; Eyer, Peter; Buckley, Nick

    2006-01-01

    Acute organophosphate (OP) pesticide poisoning causes tens of thousands of deaths each year across the developing world. Standard treatment involves the administration of intravenous atropine and oxime to counter acetylcholinesterase inhibition at the synapse. The usefulness of oximes, such as pralidoxime and obidoxime, has however been challenged over the past 20 years by physicians in many parts of the world who have failed to see benefit in their clinical practice. We have carried out a systematic review to find randomised controlled trials (RCTs) of oximes in OP poisoning. Two RCTs have been published involving 182 patients treated with pralidoxime. The RCTs did not find benefit with pralidoxime and have been used to argue that pralidoxime should not be used in OP poisoning. These physicians must be congratulated for attempting important studies in a difficult environment. However, the studies did not take into account recently clarified issues important for outcome and the published methodology is unclear, therefore such a generalised statement cannot be supported by the published results. There are many reasons why oximes may not be relevant in the overwhelming self-poisoning typical of the tropics. However, we believe that a large RCT is required to compare the current WHO-recommended pralidoxime regimen (>30mg/kg bolus followed by >8mg/kg/hr infusion) with placebo to determine definitively the role of oxime therapy in OP self-poisoning. Such a study will need to be designed with pre-defined subgroup analysis to allow the identification of patient subgroups that may benefit from oximes. PMID:11978898

  8. TRPA1 channel mediates organophosphate-induced delayed neuropathy

    PubMed Central

    Ding, Qiang; Fang, Sui; Chen, Xueqin; Wang, Youxin; Li, Jian; Tian, Fuyun; Xu, Xiang; Attali, Bernard; Xie, Xin; Gao, Zhaobing

    2017-01-01

    The organophosphate-induced delayed neuropathy (OPIDN), often leads to paresthesias, ataxia and paralysis, occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate (OP) insecticides or nerve agents, and may contribute to the Gulf War Syndrome. The acute phase of OP poisoning is often attributed to acetylcholinesterase inhibition. However, the underlying mechanism for the delayed neuropathy remains unknown and no treatment is available. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) mediates OPIDN. A variety of OPs, exemplified by malathion, activates TRPA1 but not other neuronal TRP channels. Malathion increases the intracellular calcium levels and upregulates the excitability of mouse dorsal root ganglion neurons in vitro. Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors, which resembles OPIDN. Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene. In the classic hens OPIDN model, malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate (TOCP), which also activates TRPA1 channel. Treatment with HC030031 reduces the damages caused by malathion or tri-ortho-cresyl phosphate. Duloxetine and Ketotifen, two commercially available drugs exhibiting TRPA1 inhibitory activity, show neuroprotective effects against OPIDN and might be used in emergency situations. The current study suggests TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN. PMID:28894590

  9. Organophosphate ester flame retardant-induced acute intoxications in dogs.

    PubMed

    Lehner, Andreas F; Samsing, Francisca; Rumbeiha, Wilson K

    2010-12-01

    Flame retardants have wide industrial applications and are incorporated into articles found in automobiles and home environments, including seat cushions. These compounds differ widely chemically and in their toxic potential. We report here two cases involving dogs following ingestion of car seat cushions impregnated with organophosphate ester fire retardants. Two case reports are presented. Two adult American Pit Bull dogs were presented at an emergency clinic with acute signs of central nervous system excitation including seizures. The most severely affected dog died 15 min after presentation, while the less affected dog fully recovered following treatment. In the second case, both a German Shepherd and a Rottweiler were found dead in the morning after they were left in a car overnight. A comprehensive toxicological analysis of samples from both cases revealed the presence of significant amounts (>2 ppm) of tris(2-chloroethyl)phosphate (TCEP) in stomach contents. This compound is a known inducer of epileptic seizures. Some other structurally related organophosphate ester compounds were found, and their role in the acute intoxications reported here is not known and remains to be determined. This is the first report linking acute deaths in dogs to the ingestion of car seat cushions found to contain large amounts of TCEP, an organophosphate ester compound. It is highly likely that this compound caused death through its known seizure-inducing activity.

  10. Phase II study of magnesium sulfate in acute organophosphate pesticide poisoning.

    PubMed

    Basher, A; Rahman, S H; Ghose, A; Arif, S M; Faiz, M A; Dawson, A H

    2013-01-01

    Acute organophosphorus (OP) poisoning is relatively common and a major cause of death from poisoning in developing countries. Magnesium has been shown to be of benefit in animal models. We conducted a phase II study of bolus doses of (MgSO4) in 50 patients with acute organophosphate poisoning. Patients eligible for inclusion had ingested OP and had cholinergic symptoms consistent with moderate or severe poisoning. All patients received standard care of atropinization titrated to control muscarinic symptoms and pralidoxime. The trial was run in 4 sequential groups of patients. Participants in each group received a different total dose of MgSO4 (20%) administered as intermittent bolus doses infused over 10-15 min or placebo. There was one control patient for every 4 patients who received MgSO4. Group A (16 patients) received a total of 4 gm MgSO4 as a single bolus, group B (8 patients) received 8 gm (in two 4 gm doses q4H), group C (8 patients) received 12 gm (in three 4 gm doses q4H) group D (8 patients) received 16 gm (in four 4 gm doses q4H) and control (10 patients) received placebo). Patients were closely monitored for any adverse reaction like significant clinical neuromuscular disturbance and respiratory depression. No adverse reactions to magnesium were observed. The 24 hour urinary magnesium concentration were statistically different between 16 gm (234.74 ± 74.18 mg/dl) and control (118.06 ± 30.76 mg/dl) (p = 0.019), while it was much lower than the 80% of the intravenous magnesium load. Six patients died in control group compared to 3 in 4 gm, 2 in 8 gm and 1 in 12 gm group. There was no mortality in 16 gm group. Magnesium was well tolerated in this study. Larger studies are required to examine for efficacy.

  11. Is there a role for progesterone in the management of acute organophosphate poisoning during pregnancy?

    PubMed

    Jafarzadeh, Mostafa; Nasrabadi, Zeynab Nasri; Sheikhazadi, Ardeshir; Abbaspour, Abdollah; Vasigh, Shayesteh; Yousefinejad, Vahid; Marashi, Sayed Mahdi

    2013-06-01

    Organophosphates are commonly used pesticides and cause about one million unintentional and 2 million suicidal exposures with up to 300,000 fatalities every year around the world. Toxicity of organophosphates is due to inhibition cholinesterase activity and prolonging the effects of acetylcholine in the receptor site. Clinical features of organophosphate poisoning are defecation, urination, miosis, bronchorrhea, emesis, lacrimation and salivation. Spontaneous abortion reported some when in pregnant patients. Intravenous administration of benzodiazepines, atropine and pralidoxime is the formal treatment of this toxicity. Atropine and pralidoxime have been assigned to pregnancy class C by the FDA and should be recommended for use in pregnant women clinically suffer organophosphate poisoning. Benzodiazepines have been assigned to pregnancy class D and should be avoided during pregnancy. Clinical experiments suggest transplacental transfer of organophosphates is possible, and fetal sensitivity is probable, but a single acute overdose most likely don't make any physical deformities, therefore termination of pregnancy is not imperative. Nonetheless, no definite strategy focused on maintaining pregnancy. Here we propose an idea that in any female case of acute organophosphate poisoning in childbearing range of age, maternal serum Beta-HCG should be tested for pregnancy and prophylactic progesterone should be used in pregnant cases of organophosphate poisoning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. ORGANOPHOSPHATE PESTICIDE DEGRADATION PATHWAYS DURING DRINKING WATER TREATMENT

    EPA Science Inventory

    Free chlorine has been found to react with organophosphate (OP) pesticides resulting in the more toxic oxon products. We will discuss OP pesticide degradation pathways and modeling in the presence of chlorine and chloramines, as well as present a relationship between structure a...

  13. Neuropsychological and psychiatric functioning in sheep farmers exposed to low levels of organophosphate pesticides

    PubMed Central

    Ross, Sarah Jane Mackenzie; Brewin, Chris Ray; Curran, Helen Valerie; Furlong, Clement Eugene; Abraham-Smith, Kelly Michelle; Harrison, Virginia

    2011-01-01

    The study aim was to determine whether low level exposure to organophosphate pesticides (OPs) causes neuropsychological or psychiatric impairment. Methodological weaknesses of earlier studies were addressed by: recruiting participants who had retired on ill health grounds; excluding participants with a history of acute poisoning, medical or psychiatric conditions that might account for ill health; and exploring factors which may render some individuals more vulnerable to the effects of OPs than others. Performance on tests of cognition and mood of 127 exposed sheep farmers (67 working, 60 retired) was compared with 78 unexposed controls (38 working, 40 retired) and published test norms derived from a cross section of several thousand adults in the general population. Over 40% of the exposed cohort reported clinically significant levels of anxiety and depression compared to less than 23% of controls. Exposed subjects performed significantly worse than controls and standardisation samples on tests of memory, response speed, fine motor control, mental flexibility and strategy making, even after controlling for the effects of mood. The pattern was similar for both working and retired groups. The cognitive deficits identified cannot be attributed to mood disorder, malingering, a history of acute exposure or genetic vulnerability in terms of PON1192 polymorphisms. Results suggest a relationship may exist between low level exposure to organophosphates and impaired neurobehavioural functioning and these findings have implications for working practice and for other occupational groups exposed to OPs such as aviation workers and Gulf War veterans. PMID:20227490

  14. Quantitative Structure-Activity Relationships for Organophosphate Enzyme Inhibition (Briefing Charts)

    DTIC Science & Technology

    2011-09-22

    OPs) are a group of pesticides that inhibit enzymes such as acetylcholinesterase. Numerous OP structural variants exist and toxicity data can be...and human toxicity studies especially for OPs lacking experimental data. 15. SUBJECT TERMS QSAR Organophosphates...structure and mechanism of toxicity c) Linking QSAR and OP PBPK/PD 2. Methods a) Physiochemical Descriptors b) Regression Techniques 3. Results a

  15. Efficacy of fresh packed red blood transfusion in organophosphate poisoning.

    PubMed

    Bao, Hang-Xing; Tong, Pei-Jian; Li, Cai-Xia; Du, Jing; Chen, Bing-Yu; Huang, Zhi-Hui; Wang, Ying

    2017-03-01

    The mortality rate caused by organophosphate (OP) poisoning is still high, even the standard treatment such as atropine and oxime improves a lot. To search for alternative therapies, this study was aimed to investigate the effects of packed red blood cell (RBC) transfusion in acute OP poisoning, and compare the therapeutic effects of RBCs at different storage times.Patients diagnosed with OP poisoning were included in this prospective study. Fresh RBCs (packed RBCs stored less than 10 days) and longer-storage RBCs (stored more than 10 days but less than 35 days) were randomly transfused or not into OP poisoning patients. Cholinesterase (ChE) levels in blood, atropine usage and durations, pralidoxime durations were measured.We found that both fresh and longer-storage RBCs (200-400 mL) significantly increased blood ChE levels 6 hours after transfusion, shortened the duration for ChE recovery and length of hospital stay, and reduced the usage of atropine and pralidoxime. In addition, fresh RBCs demonstrated stronger therapeutic effects than longer-storage RBCs.Packed RBCs might be an alternative approach in patients with OP poisoning, especially during early stages.

  16. ORGANOPHOSPHATE PESTICIDE EXPOSURES - WHERE ARE THE HIGH RISK CHILDREN?

    EPA Science Inventory

    Methods to identify children at high-risk for organophosphate (OP) pesticide exposure are difficult to develop because biological markers reflect only recent "snapshots" of exposure due to the short half-life of OP compounds (generally about 24 hours). We conducted a series of p...

  17. BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF ACUTE CHLORPYRIFOS IN RATS: TOLERANCE TO PROLONGED INHIBITION OF CHOLINESTERASE

    EPA Science Inventory

    Chlorpyrifos (CPF), a commercially prevalent organophosphate (OP) pesticide, inhibits blood and brain cholinesterase for up to 10 weeks after acute s.c. injection in rats. his prolonged inhibition suggested that acute CPF may affect muscarinic receptors and behavior as does repea...

  18. Technetium-99m diethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity: experimental study.

    PubMed

    Yavuz, Yucel; Kaya, Eser; Yurumez, Yusuf; Sahin, Onder; Bas, Orhan; Fidan, Huseyin; Sezer, Murat

    2008-09-01

    The aim of this experimental study was to investigate pathological signs of lung damages caused by acute organophosphate (OP) poisoning by using Tc-99m DTPA radioaerosol scintigraphy and histopathological investigation. Fourteen rabbits were divided into two equal groups (n = 7). Group 1 (control group) received normal saline (same volume of fenthion, 2 ml/kg) via orogastric tube. Group 2 (OP toxicity group) received 150 mg/kg of fenthion (diluted fenthion, 2 ml/kg) via orogastric tube. Six hours later, Tc-99m-DTPA aerosol inhalation lung scintigraphy was performed in both groups. Then all rabbits were anesthetized with ketamine hydrochloride (35 mg/kg, i.p.) and xysilazine (5 mg/kg, i.p.), and sacrificed by intracardiac blood discharge. The lungs were then removed. There was a significant difference in T1/2 values of Tc-99m DTPA clearance between control group and OP toxicity group (p = 0.04). Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar, and bronchial lumen, alveolar destruction, emphysematous changes, and bronchoalveolar hemorrhage scores were significantly higher in the rabbits exposed to OP compared with the control group (p < 0.05). This study showed that OP toxicity caused a decrease in the alveolar clearance. Tc-99m DTPA radioaerosol inhalation lung scintigraphy was found to be a sensitive determination of acute lung damage in OP poisoning.

  19. Midazolam as an anticonvulsant antidote for organophosphate intoxication− A pharmacotherapeutic appraisal

    PubMed Central

    Reddy, Sandesh D.; Reddy, Doodipala Samba

    2015-01-01

    SUMMARY Objective This review summarizes the therapeutic potential of midazolam as an anticonvulsant antidote for organophosphate (OP) intoxication. Methods Benzodiazepines are widely used for acute seizures and status epilepticus (SE), a neurological emergency of persistent seizures that can lead to severe neuronal damage or death. Midazolam is a benzodiazepine hypnotic with a rapid onset and short duration of action. Results Midazolam is considered the new drug of choice for persistent acute seizures and SE, including those caused by neurotoxic OPs and nerve agents. Midazolam is a positive allosteric modulator of synaptic GABA-A receptors in the brain. It potentiates GABAergic inhibition and thereby controls hyperexcitability and seizures. Midazolam is administered intravenously or intramuscularly to control acute seizures and SE. Due to its favorable pharmacokinetic features, midazolam is being considered as a replacement anticonvulsant for diazepam in the antidote kit for nerve agents. Clinical studies such as the recent RAMPART trial have confirmed the anticonvulsant efficacy of midazolam in SE in prehospital settings. Significance In experimental models, midazolam is effective when given at the onset of seizures caused by nerve agents. However, benzodiazepines are less effective at terminating seizures when given 30 min or later after OP exposure or seizure onset likely because of internalization or down-regulation of synaptic, but not extrasynaptic, GABA-A receptors, which can lead to diminished potency and seizure recurrence. PMID:26032507

  20. Semen quality in Peruvian pesticide applicators: association between urinary organophosphate metabolites and semen parameters

    PubMed Central

    Yucra, Sandra; Gasco, Manuel; Rubio, Julio; Gonzales, Gustavo F

    2008-01-01

    Background Organophosphates are broad class of chemicals widely used as pesticides throughout the world. We performed a cross-sectional study of associations between dialkylphosphate metabolites of organophosphates and semen quality among pesticide applicators in Majes (Arequipa), Peru. Methods Thirty-one men exposed to organophosphate (OP) pesticides and 31 non-exposed were recruited (age, 20–60 years). In exposed subjects, semen and a blood sample were obtained one day after the last pesticide application. Subjects were grouped according to levels of OP metabolites in urine. Semen samples were analyzed for sperm concentration, percentage of sperm motility, percentage of normal morphology, semen leucocytes and concentrations of fructose and zinc. Exposure to OP was assessed by measuring six urinary OP metabolites (dimethyl and diethyl phosphates and thiophosphates) by gas chromatography using a single flame photometric detector. Results Diethyldithiophosphate (p = 0.04) and diethylthiophosphate (p = 0.02) better reflected occupational pesticide exposure than other OP metabolites. Semen analysis revealed a significant reduction of semen volume and an increase in semen pH in men with OP metabolites. Multiple regression analysis showed that both occupational exposure to pesticides and the time of exposure to pesticides were more closely related to alterations in semen quality parameters than the single measurement of OP metabolites in urine. Conclusion The study demonstrated that occupational exposure to OP pesticides was more closely related to alterations in semen quality than a single measurement of urine OP metabolites. Current measurement of OP metabolites in urine may not reflect the full risk. PMID:19014632

  1. Acute methaemoglobinaemia initially treated as organophosphate poisoning leading to atropine toxicity.

    PubMed

    Kakhandki, Srinivas; Yahya, Mohammed; Praveen, Mudalgi

    2012-07-01

    A case of unknown compound poisoning is presented. It was initially treated as organophosphate poisoning with lack of response. A timely diagnosis of acute methaemoglobinaemia and iatrogenic atropine toxicity was made based on clinical evaluation. Treatment of methaemoglobinaemia using oral methylene blue and of atropine toxicity with supportive measures could save the patient.

  2. DETERMINING ACTIVE OXIDANT SPECIES REACTING WITH ORGANOPHOSPHATE PESTICIDES IN CHLORINATED DRINKING WATER

    EPA Science Inventory

    Chlorpyrifos (CP) is an organophosphate (OP) pesticide that was used as a model compound to investigate the transformation of OP pesticides at low pH and in the presence of bromide and natural organic matter (NOM) under drinking water treatment conditions. Raman spectroscopy was...

  3. The use of self-reported symptoms as a proxy for acute organophosphate poisoning after exposure to chlorpyrifos 50% plus cypermethrin 5% among Nepali farmers: a randomized, double-blind, placebo-controlled, crossover study.

    PubMed

    Kofod, Dea Haagensen; Jørs, Erik; Varma, Anshu; Bhatta, Shankuk; Thomsen, Jane Frølund

    2016-12-13

    Previous studies stating a high prevalence of occupational acute pesticide poisoning in developing countries have mainly relied on measurements of the rather non-specific self-reported acute pesticide poisoning symptoms. Only a few studies have measured the biomarker plasma cholinesterase (PchE) activity, in addition to the symptoms, when assessing occupational acute pesticide poisoning. This study evaluated self-reported symptoms as a proxy for acute organophosphate poisoning among Nepali farmers by examining self-reported acute organophosphate poisoning symptoms and PchE activity in response to occupational acute organophosphate exposure. We performed a randomized, double-blind, placebo-controlled, crossover trial among 42 Nepali commercial vegetable farmers. The farmers were randomly assigned (ratio 1:1) to a 2-h organophosphate (chlorpyrifos 50% plus cypermethrin 5%: moderately hazardous) spray session or a 2-h placebo spray session, and after 7 days' washout, the farmers were assigned to the other spray session. Before and after each spray session farmers were interviewed about acute organophosphate poisoning symptoms and PchE activity was measured. Analyses were conducted with a Two Sample T-test and Mann Whitney U-test. We found no difference in the symptom sum or PchE activity from baseline to follow up among farmers spraying with organophosphate (symptom sum difference -1, p = 0.737; PchE mean difference 0.02 U/mL, p = 0.220), placebo (symptom sum difference 9, p = 0.394; PchE mean difference 0.02 U/mL, p = 0.133), or when comparing organophosphate to placebo (symptom p = 0.378; PchE p = 0.775). However, a high percentage of the farmers reported having one or more symptoms both at baseline and at follow up in the organophosphate spray session (baseline 47.6%, follow up 45.2%) and placebo spray session (baseline 35.7%, follow up 50.0%), and 14.3% of the farmers reported three or more symptoms after the organophosphate spray session

  4. The Association Between Ambient Exposure to Organophosphates and Parkinson’s Disease Risk

    PubMed Central

    Wang, Anthony; Cockburn, Myles; Ly, Thomas T.; Bronstein, Jeff; Ritz, Beate

    2014-01-01

    Objectives There is a general consensus that pesticides are involved in the etiology of Parkinson’s disease (PD), although associations between specific pesticides and the risk of developing Parkinson’s disease have not been well studied. This study examines the risk of developing PD associated with specific organophosphate pesticides and their mechanisms of toxicity. Methods This case-control study uses a geographic information system (GIS)-based exposure assessment tool to estimate ambient exposure to 36 commonly used organophosphates (OPs) from 1974-1999. All selected OPs were analyzed individually and also in groups formed according to their presumed mechanisms of toxicity. Results The study included 357 incident PD cases and 752 population controls living in the Central Valley of California. Ambient exposure to each OP evaluated separately increased the risk of developing PD. However, most participants were exposed to combinations of OPs rather than a single pesticide. Risk estimates for OPs grouped according to different presumed functionalities and toxicities were similar and did not allow us to distinguish between them. However, we observed exposure-response patterns with exposure to an increasing number of OPs. Conclusions This study adds strong evidence that OPs are implicated in the etiology of idiopathic PD. However, studies of OPs at low doses reflective of real-world ambient exposure are needed to determine the mechanisms of neurotoxicity. PMID:24436061

  5. ORGANOPHOSPHATE PESTICIDE DEGRADATION UNDER DRINKING WATER TREATMENT CONDITIONS

    EPA Science Inventory

    Chlorpyrifos (CP) was used as a model compound to develop experimental methods and prototype modeling tools to forecast the fate of organophosphate (OP) pesticides under drinking water treatment conditions. CP was found to rapidly oxidize to chlorpyrifos oxon (CPO) in the presen...

  6. MICROCHIP ENZYMATIC ASSAY OF ORGANOPHOSPHATE NERVE AGENTS. (R830900)

    EPA Science Inventory

    An on-chip enzymatic assay for screening organophosphate (OP) nerve agents, based on a pre-column reaction of organophosphorus hydrolase (OPH), electrophoretic separation of the phosphonic acid products, and their contactless-conductivity detection, is described. Factors affec...

  7. Exposure to organophosphate (OP) pesticides and health conditions in agricultural and non-agricultural workers from Maule, Chile

    PubMed Central

    Muñoz-Quezada, María Teresa; Lucero, Boris; Iglesias, Verónica; Levy, Karen; Muñoz, María Pía; Achú, Eduardo; Cornejo, Claudia; Concha, Carlos; Brito, Ana María; Villalobos, Marcos

    2017-01-01

    The objective was to evaluate the characteristics of exposure to OP pesticides and health status in Chilean farm workers from the Maule Region. An occupational health questionnaire was administered in 207 agricultural and non-agricultural workers. For the group of agricultural workers we asked about specific occupational exposure history and symptoms of OP pesticide poisoning. The main health problem of the exposed group was previous OP pesticide poisoning (p <0.001). Fifty-six percent of agricultural workers reported symptoms consistent with acute OP pesticide poisoning. The use of respiratory personal protective equipment and younger age were protective against these symptoms, and number of years of OP pesticide exposure was positively associated with reporting symptoms of poisoning. Of the pesticide applicators 47% reported using chlorpyrifos. The regulations regarding use and application of pesticides should be strengthened, as should training and intervention with workers to improve the use of personal protective equipment. PMID:28002976

  8. Exposure to organophosphate (OP) pesticides and health conditions in agricultural and non-agricultural workers from Maule, Chile.

    PubMed

    Muñoz-Quezada, María Teresa; Lucero, Boris; Iglesias, Verónica; Levy, Karen; Muñoz, María Pía; Achú, Eduardo; Cornejo, Claudia; Concha, Carlos; Brito, Ana María; Villalobos, Marcos

    2017-02-01

    The objective was to evaluate the characteristics of exposure to OP pesticides and health status in Chilean farm workers from the Maule Region. An occupational health questionnaire was administered in 207 agricultural and non-agricultural workers. For the group of agricultural workers, we asked about specific occupational exposure history and symptoms of OP pesticide poisoning. The main health problem of the exposed group was previous OP pesticide poisoning (p < 0.001). Fifty-six percent of agricultural workers reported symptoms consistent with acute OP pesticide poisoning. The use of respiratory personal protective equipment and younger age were protective against these symptoms, and number of years of OP pesticide exposure was positively associated with reporting symptoms of poisoning. Of the pesticide applicators 47 % reported using chlorpyrifos. The regulations regarding use and application of pesticides should be strengthened, as should training and intervention with workers to improve the use of personal protective equipment.

  9. Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.

    PubMed

    Suratman, Suratman; Edwards, John William; Babina, Kateryna

    2015-01-01

    Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.

  10. Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment.

    PubMed

    Swiercz, Radosław; Lutz, Piotr; Gralewicz, Sławomir; Grzelińska, Zofia; Piasecka-Zelga, Joanna; Wąsowicz, Wojciech

    2013-08-01

    Organophosphates are cholinesterase (ChE) inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours) rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP) poisoning symptomatology. In rodents, corticosterone (CORT) is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentration (the CORT response) and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET) [2-methyl-1,2-di(pyridin-3-yl)propan-1-one] blocks CORT synthesis by inhibiting steroid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP) [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. The purpose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. The following was observed in the MET-treated rats: i) no rise in plasma CORT concentration after the CVP administration, ii) a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

  11. The Long-Term Effects of Organophosphates Poisoning as a Risk Factor of CVDs: A Nationwide Population-Based Cohort Study

    PubMed Central

    Lin, Cheng-Li; Chang, Shih-Yu; Sung, Fung-Chang; Tai, Sally C. W.

    2015-01-01

    Background Organophosphorus pesticides are widely used throughout the world. Because of their ease of availability, organophosphorus compounds are commonly used for self-poisoning in developing countries. The acute effects of exposure to organophosphorus pesticides are well known, but the chronic effects are unclear. Recent studies suggest that abnormalities of the central and peripheral nervous systems persisted for up to 5 years after acute poisoning due to a single large dose of organophosphates (OPs). However, the long-term effects on cardiovascular diseases are poorly understood. Methodology/Principal Findings An OPs-exposed cohort (N = 7,561) and an age- and gender-matched control cohort (N = 30,244), both identified from the National Health Insurance Research Database, were compared. We utilized the multivariable Cox proportional model to estimate the risks of developing arrhythmia, coronary artery disease (CAD) and congestive heart failure (CHF). The patients with acute poisoning from OPs had higher incidence rates of arrhythmia (5.89 vs. 3.61 per 1,000 person-years), CAD (9.10 vs. 6.88 per 1,000 person-years), and CHF (3.89 vs. 2.98 per 1,000 person-years) compared with that of the non-OPs poisoning cohort, with a crude subhazard ratio (SHR) of 1.40, 1.13, and 1.12, respectively. Additionally, a significantly higher risk of arrhythmia was observed in the OPs poisoning cohort (adjusted SHR = 1.25) compared with the non-OPs poisoning cohort, particularly in male patients (adjusted SHR = 1.33) and those under 49 years of age (adjusted SHR = 3.16). After accounting for the competing risks of death, there was a higher risk of arrhythmia and CAD during a three year follow-up period (adjusted SHR = 1.50 for arrhythmia; adjusted SHR = 1.10 for CAD). We also found an adjusted SHR of 1.36 associated with developing CHF after 6 years of follow-up for OPs poisoning cohort. Conclusions Acute OPs poisoning may continuously impact human health through mechanisms that are

  12. INCREASED SUSCEPTIBILITY OF THE SPONTANEOUSLY HYPERTENSIVE RAT TO CHLORPYRIFOS, AN ORGANOPHOSPHATE PESTICIDE.

    EPA Science Inventory

    Hypertension and hypothermia are common symptoms in rats exposed to chlorpyrifos (CHP), an organophosphate (OP)-based pesticide. CHP inhibits acetylcholinesterase (AChE) activity resulting in central and peripheral stimulation of cholinergic pathways involved in blood pressure ...

  13. The association of alcohol consumption with patient survival after organophosphate poisoning: a multicenter retrospective study.

    PubMed

    Lee, Young Hwan; Oh, Young Taeck; Lee, Won Woong; Ahn, Hee Cheol; Sohn, You Dong; Ahn, Ji Yun; Min, Yong Hun; Kim, Hyun; Lim, Seung Wook; Lee, Kui Ja; Shin, Dong Hyuk; Park, Sang O; Park, Seung Min

    2017-06-01

    Organophosphate (OP) intoxication remains a serious worldwide health concern, and many patients with acute OP intoxication have also consumed alcohol. Therefore, we evaluated the association of blood alcohol concentration (BAC) with mortality among patients with OP intoxication. We retrospectively reviewed records from 135 patients who were admitted to an emergency department (ED) for OP intoxication between January 2000 and December 2012. Factors that were associated with patient survival were identified via receiver operating characteristic curve, multiple logistic regression, and Kaplan-Meier survival analyses. Among 135 patients with acute OP poisoning, 112 patients survived (overall mortality rate: 17 %). The non-survivors also exhibited a significantly higher BAC, compared to the survivors [non-survivors: 192 mg/dL, interquartile range (IQR) 97-263 mg/dL vs. survivors: 80 mg/dL, IQR 0-166.75 mg/dL; p < 0.001]. A BAC cut-off value of 173 mg/dL provided an area under the curve of 0.744 [95 % confidence interval (CI) 0.661-0.815], a sensitivity of 65.2 %, and a specificity of 81.2 %. A BAC of >173 mg/dL was associated with a significantly increased risk of 6-month mortality in the multiple logistic regression model (odds ratio 4.92, 95 % CI 1.45-16.67, p = 0.001). The Cox proportional hazard model revealed that a BAC of >173 mg/dL provided a hazard ratio of 3.07 (95 % CI 1.19-7.96, p = 0.021). A BAC of >173 mg/dL is a risk factor for mortality among patients with OP intoxication.

  14. Organophosphate-induced changes in the PKA regulatory function of Swiss Cheese/NTE lead to behavioral deficits and neurodegeneration.

    PubMed

    Wentzell, Jill S; Cassar, Marlène; Kretzschmar, Doris

    2014-01-01

    Organophosphate-induced delayed neuropathy (OPIDN) is a Wallerian-type axonopathy that occurs weeks after exposure to certain organophosphates (OPs). OPs have been shown to bind to Neuropathy Target Esterase (NTE), thereby inhibiting its enzymatic activity. However, only OPs that also induce the so-called aging reaction cause OPIDN. This reaction results in the release and possible transfer of a side group from the bound OP to NTE and it has been suggested that this induces an unknown toxic function of NTE. To further investigate the mechanisms of aging OPs, we used Drosophila, which expresses a functionally conserved orthologue of NTE named Swiss Cheese (SWS). Treating flies with the organophosporous compound tri-ortho-cresyl phosphate (TOCP) resulted in behavioral deficits and neurodegeneration two weeks after exposure, symptoms similar to the delayed effects observed in other models. In addition, we found that primary neurons showed signs of axonal degeneration within an hour after treatment. Surprisingly, increasing the levels of SWS, and thereby its enzymatic activity after exposure, did not ameliorate these phenotypes. In contrast, reducing SWS levels protected from TOCP-induced degeneration and behavioral deficits but did not affect the axonopathy observed in cell culture. Besides its enzymatic activity as a phospholipase, SWS also acts as regulatory PKA subunit, binding and inhibiting the C3 catalytic subunit. Measuring PKA activity in TOCP treated flies revealed a significant decrease that was also confirmed in treated rat hippocampal neurons. Flies expressing additional PKA-C3 were protected from the behavioral and degenerative phenotypes caused by TOCP exposure whereas primary neurons were not. In addition, knocking-down PKA-C3 caused similar behavioral and degenerative phenotypes as TOCP treatment. We therefore propose a model in which OP-modified SWS cannot release PKA-C3 and that the resulting loss of PKA-C3 activity plays a crucial role in developing

  15. Organophosphate-Induced Changes in the PKA Regulatory Function of Swiss Cheese/NTE Lead to Behavioral Deficits and Neurodegeneration

    PubMed Central

    Kretzschmar, Doris

    2014-01-01

    Organophosphate-induced delayed neuropathy (OPIDN) is a Wallerian-type axonopathy that occurs weeks after exposure to certain organophosphates (OPs). OPs have been shown to bind to Neuropathy Target Esterase (NTE), thereby inhibiting its enzymatic activity. However, only OPs that also induce the so-called aging reaction cause OPIDN. This reaction results in the release and possible transfer of a side group from the bound OP to NTE and it has been suggested that this induces an unknown toxic function of NTE. To further investigate the mechanisms of aging OPs, we used Drosophila, which expresses a functionally conserved orthologue of NTE named Swiss Cheese (SWS). Treating flies with the organophosporous compound tri-ortho-cresyl phosphate (TOCP) resulted in behavioral deficits and neurodegeneration two weeks after exposure, symptoms similar to the delayed effects observed in other models. In addition, we found that primary neurons showed signs of axonal degeneration within an hour after treatment. Surprisingly, increasing the levels of SWS, and thereby its enzymatic activity after exposure, did not ameliorate these phenotypes. In contrast, reducing SWS levels protected from TOCP-induced degeneration and behavioral deficits but did not affect the axonopathy observed in cell culture. Besides its enzymatic activity as a phospholipase, SWS also acts as regulatory PKA subunit, binding and inhibiting the C3 catalytic subunit. Measuring PKA activity in TOCP treated flies revealed a significant decrease that was also confirmed in treated rat hippocampal neurons. Flies expressing additional PKA-C3 were protected from the behavioral and degenerative phenotypes caused by TOCP exposure whereas primary neurons were not. In addition, knocking-down PKA-C3 caused similar behavioral and degenerative phenotypes as TOCP treatment. We therefore propose a model in which OP-modified SWS cannot release PKA-C3 and that the resulting loss of PKA-C3 activity plays a crucial role in developing

  16. Cardiac effects of magnesium sulfate pretreatment on acute dichlorvos-induced organophosphate poisoning: an experimental study in rats.

    PubMed

    Gunay, Nurullah; Kekec, Zeynep; Demiryurek, Seniz; Kose, Ataman; Namiduru, Emine S; Gunay, Nahide E; Sari, Ibrahim; Demiryurek, Abdullah T

    2010-02-01

    Although atropine and oximes are traditionally used in the management of organophosphate poisoning, investigations have been directed to finding additional therapeutic approaches. Thus, the aim of this study was to evaluate the cardiac effects of magnesium sulfate pretreatment on dichlorvos intoxication in rats. Rats were randomly divided into three groups as control, dichlorvos, and magnesium sulfate groups. After 6 h of dichlorvos or corn oil (as a vehicle) injection, venous blood samples were collected, and cardiac tissue samples were obtained. Biochemical analyses were performed to measure some parameters on serum and cardiac tissue. Immunohistochemical analyses of apoptosis and inducible nitric oxide (NO) synthase showed no change in cardiac tissue. Serum cholinesterase levels were markedly depressed with dichlorvos, and further suppressed markedly with magnesium sulfate pretreatment. Although we have demonstrated that serum NO levels in dichlorvos and magnesium sulfate groups were lower than the control group, cardiac tissue NO levels in magnesium sulfate group were higher than the other two groups. Mortality was not significantly affected with magnesium sulfate pretreatment. Uncertainty still persists on the right strategies for the treatment of organophosphate acute poisoning; however, it was concluded that our results do not suggest that magnesium sulfate therapy is beneficial in the management of acute dichlorvos-induced organophosphate poisoning, and also further studies are required.

  17. Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine treatment.

    PubMed

    Shrot, Shai; Ramaty, Erez; Biala, Yoav; Bar-Klein, Guy; Daninos, Moshe; Kamintsky, Lyn; Makarovsky, Igor; Statlender, Liran; Rosman, Yossi; Krivoy, Amir; Lavon, Ophir; Kassirer, Michael; Friedman, Alon; Yaari, Yoel

    2014-09-02

    Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450μg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

    PubMed Central

    Antonijevic, Biljana; Stojiljkovic, Milos P.

    2007-01-01

    The use of organophosphorus pesticides results in toxicity risk to non-target organisms. Organophosphorus compounds share a common mode of action, exerting their toxic effects primarily via acetylcholinesterase (AChE) inhibition. Consequently, acetylcholine accumulates in the synaptic clefts of muscles and nerves, leading to overstimulation of cholinergic receptors. Acute cholinergic crisis immediately follows exposure to organophosphate and includes signs and symptoms resulting from hyperstimulation of central and peripheral muscarinic and nicotinic receptors. The current view of the treatment of organophosphate poisoning includes three strategies, i.e. the use of an anticholinergic drug (e.g., atropine), cholinesterase-reactivating agents (e.g., oximes) and anticonvulsant drugs (e.g., benzodiazepines). Oximes, as a part of antidotal therapy, ensure the recovery of phosphylated enzymes via a process denoted as reactivation of inhibited AChE. However, both experimental results and clinical findings have demonstrated that different oximes are not equally effective against poisonings caused by structurally different organophosphorus compounds. Therefore, antidotal characteristics of conventionally used oximes can be evaluated regarding how close the certain substance is to the theoretical concept of the universal oxime. Pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LüH-6), HI-6 and HLö-7 have all been demonstrated to be very effective in experimental poisonings with sarin and VX. TMB-4 and LüH-6 may reactivate tabun-inhibited AChE, whereas HI-6 possesses the ability to reactivate the soman-inhibited enzyme. An oxime HLö-7 seems to be an efficient reactivator of AChE inhibited by any of the four organophosphorus warfare agents. According to the available literature, the oximes LüH-6 and TMB-4, although relatively toxic, are the most potent to induce reactivation of AChE inhibited by the majority of organophosphorus pesticides. Since there are no reports of

  19. Neuregulin-1 is Neuroprotective in a Rat Model of Organophosphate-Induced Delayed Neuronal Injury

    PubMed Central

    Li, Yonggang; Lein, Pamela J.; Liu, Cuimei; Bruun, Donald A.; Giulivi, Cecilia; Ford, Gregory; Tewolde, Teclemichael; Ross-Inta, Catherine; Ford, Byron D.

    2012-01-01

    Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. PMID:22583949

  20. Mechanism-Based Analysis of Acetylcholinesterase Inhibitory Potency of Organophosphates, Carbamates, and Their Analogs

    EPA Science Inventory

    Acetylcholinesterase (AChE) is a key enzyme in the nervous system of animals, terminating impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine. Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a s...

  1. Association between blood cholinesterase activity, organophosphate pesticide residues on hands, and health effects among chili farmers in Ubon Ratchathani Province, northeastern Thailand

    PubMed

    Nganchamung, Thitirat; Robson, Mark G; Siriwong, Wattasit

    Use of pesticides has been documented to lead to several adverse health effects. Farmers are likely to be exposed to pesticides through dermal exposure as a result of mixing, loading, and spraying. Organophosphate pesticides (OPs) are widely used in most of the agricultural areas throughout Thailand. OPs are cholinesterase inhibitors and blood cholinesterase activity is used as a biomarker of OP effects. This study aims to determine the association between blood cholinesterase activity and organophosphate pesticide residues on chili farmer’s hands and their adverse health effects. Ninety chili farmers directly involved with pesticide applications (e.g. mixing, loading, spraying) were recruited and were interviewed face to face. Both enzymes, erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (PChE), were tested with the EQM Test-mate Cholinesterase Test System (Model 400). Hand wipe samples were used for collecting residues on both hands and OP residues for chlorpyrifos and profenofos were quantified using gas chromatography equipped with a flame photometric detector (GC-FPD). The average activity (±SD) of AChE and PChE was 2.73 (±0.88) and 1.58 (±0.56) U/mL, respectively. About 80.0% of the participants had detectable OP residues on hands. The median residues of chlorpyrifos and profenofos were found to be 0.02 and 0.03 mg/kg/two hands, respectively. Half of participants reported having some acute health symptoms within 48 hours after applying pesticides. When adjusted for gender, number of years working in chili farming, and frequency of pesticide use, AChE activity (Adjusted OR = 0.03, 95%CI: 0.01-0.13) and detected OP residues on hands (Adjusted OR = 0.15, 95%CI: 0.02-0.95) were significantly associated with having health effects, but no significant association was found in PChE activity (Adjusted OR = 2.09, 95%CI: 0.63-6.99). This study suggests that regular monitoring for blood cholinesterase and effective interventions to reduce pesticide

  2. Seasonal fluctuations of organophosphate concentrations in precipitation and storm water runoff.

    PubMed

    Regnery, Julia; Püttmann, Wilhelm

    2010-02-01

    To investigate seasonal fluctuations and trends of organophosphate (flame retardants, plasticizers) concentrations in rain and snow, precipitation samples were collected in 2007-2009 period at a densely populated urban sampling site and two sparsely populated rural sampling sites in middle Germany. In addition, storm water runoff was sampled from May 2008 to April 2009 at an urban storm water holding tank (SWHT). Samples were analyzed for tris(2-chloroethyl) phosphate (TCEP), tris(2-chloro-1-methylethyl) phosphate (TCPP), tris(1,3-dichloro-2-propyl) phosphate (TDCP), tris(2-butoxyethyl) phosphate (TBEP), tri-iso-butyl phosphate (TiBP), and tri-n-butyl phosphate (TnBP) by gas chromatography-mass spectrometry after solid phase extraction. Among the six analyzed organophosphates (OPs), TCPP dominated in all precipitation and SWHT water samples with maximum concentrations exceeding 1000ngL(-1). For all analytes, no seasonal trends were observed at the urban precipitation sampling site, although atmospheric photooxidation was expected to reduce particularly concentrations of non-chlorinated OPs during transport from urban to remote areas in summer months with higher global irradiation. In the SWHT a seasonal trend with decreasing concentrations in summer/autumn is evident for the non-chlorinated OPs due to in-lake degradation but not for the chlorinated OPs. Furthermore, an accumulation of OPs deposited in SWHTs was observed with concentrations often exceeding those observed in wet precipitation. Median concentrations of TCPP (880ngL(-1)), TDCP (13ngL(-1)) and TBEP (77ngL(-1)) at the SWHT were more than twice as high as median concentrations measured at the urban precipitation sampling site (403ngL(-1), 5ngL(-1), and 21ngL(-1) respectively).

  3. A potential target for organophosphate insecticides leading to spermatotoxicity.

    PubMed

    Suzuki, Himiko; Tomizawa, Motohiro; Ito, Yuki; Abe, Keisuke; Noro, Yuki; Kamijima, Michihiro

    2013-10-16

    Organophosphate (OP) insecticides as an anticholinesterase also act on the diverse serine hydrolase targets, thereby revealing secondary or unexpected toxic effects including male reproductive toxicity. The present investigation detects a possible target molecule(s) for OP-induced spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) from a chemical standpoint. The activity-based protein profiling (ABPP) approach with a phosphonofluoridate fluorescent probe pinpointed the molecular target for fenitrothion (FNT, a major OP insecticide) oxon (bioactive metabolite of FNT) in the mouse testicular membrane proteome, i.e., FNT oxon phosphorylates the fatty acid amide hydrolase (FAAH), which plays pivotal roles in spermatogenesis and sperm motility acquirement. Subsequently, mice were treated orally with vehicle or FNT for 10 days, and FAAH activity in testis or epididymis cauda was markedly reduced by the subacute exposure. ABPP analysis revealed that FAAH was selectively inhibited among the FNT-treated testicular membrane proteome. Accordingly, FAAH is a potential target for OP-elicited spermatotoxicity.

  4. Identification of an opd (organophosphate degradation) gene in an Agrobacterium isolate.

    PubMed

    Horne, Irene; Sutherland, Tara D; Harcourt, Rebecca L; Russell, Robyn J; Oakeshott, John G

    2002-07-01

    We isolated a bacterial strain, Agrobacterium radiobacter P230, which can hydrolyze a wide range of organophosphate (OP) insecticides. A gene encoding a protein involved in OP hydrolysis was cloned from A. radiobacter P230 and sequenced. This gene (called opdA) had sequence similarity to opd, a gene previously shown to encode an OP-hydrolyzing enzyme in Flavobacterium sp. strain ATCC 27551 and Brevundimonas diminuta MG. Insertional mutation of the opdA gene produced a strain lacking the ability to hydrolyze OPs, suggesting that this is the only gene encoding an OP-hydrolyzing enzyme in A. radiobacter P230. The OPH and OpdA proteins, encoded by opd and opdA, respectively, were overexpressed and purified as maltose-binding proteins, and the maltose-binding protein moiety was cleaved and removed. Neither protein was able to hydrolyze the aliphatic OP malathion. The kinetics of the two proteins for diethyl OPs were comparable. For dimethyl OPs, OpdA had a higher k(cat) than OPH. It was also capable of hydrolyzing the dimethyl OPs phosmet and fenthion, which were not hydrolyzed at detectable levels by OPH.

  5. Selective detection of hypertoxic organophosphates pesticides via PDMS composite based acetylcholinesterase-inhibition biosensor.

    PubMed

    Zhao, Wei; Ge, Pei-Yu; Xu, Jing-Juan; Chen, Hong-Yuan

    2009-09-01

    We report on a pair of highly sensitive amperometric biosensors for organophosphate pesticides (OPs) based on assembling acetylcholinesterase (AChE) on poly(dimethylsiloxane) (PDMS)-poly(diallydimethylemmonium) (PDDA)/gold nanoparticles (AuNPs) composite film. Two AChE immobilization strategies are proposed based on the composite film with hydrophobic and hydrophilic surface tailored by oxygen plasma. The twin biosensors show interesting different electrochemical performances. The hydrophobic surface based PDMS-PDDAN AuNPs/choline oxidase (ChO)/AChE biosensor (biosensor-1) shows excellent stability and unique selectivity to hypertoxic organophosphate. At optimal conditions, this biosensor-1 could measure 5.0 x 10(-10) g/L paraoxon and 1.0 x 10(-9) g/L parathion. As for the hydrophilic surface based biosensor (biosensor-2), it shows no selectivity but can be commonly used for the detection of most OPs. Based on the structure of AChE, it is assumed that via the hydrophobic interaction between enzyme molecules and hydrophobic surface, the enzyme active sites surrounded by hydrophobic amino acids face toward the surface and get better protection from OPs. This assumption may explain the different performances of the twin biosensors and especially the unique selectivity of biosensor-1 to hypertoxic OPs. Real sample detection was performed and the omethoate residue on Cottomrose Hibiscus leaves was detected with biosensor-1.

  6. A comparison of organophosphate degradation genes and bioremediation applications.

    PubMed

    Iyer, Rupa; Iken, Brian; Damania, Ashish

    2013-12-01

    Organophosphates (OPs) form the bulk of pesticides that are currently in use around the world accounting for more than 30% of the world market. They also form the core for many nerve-based warfare agents including sarin and soman. The widespread use and the resultant build-up of OP pesticides and chemical nerve agents has led to the development of major health problems due to their extremely toxic interaction with any biological system that encounters them. Growing concern over the accumulation of OP compounds in our food products, in the soils from which they are harvested and in wastewater run-off has fuelled a growing interest in microbial biotechnology that provides cheap, efficient OP detoxification to supplement expensive chemical methods. In this article, we review the current state of knowledge of OP pesticide and chemical agent degradation and attempt to clarify confusion over identification and nomenclature of two major families of OP-degrading enzymes through a comparison of their structure and function. The isolation, characterization, utilization and manipulation of the major detoxifying enzymes and the molecular basis of degradation of OP pesticides and chemical nerve agents are discussed as well as the achievements and technological advancements made towards the bioremediation of such compounds. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

  7. BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. 1. POTENTIOMETRIC ENZYME ELECTRODE. (R823663)

    EPA Science Inventory

    A potentiometric enzyme electrode for the direct measurement of organophosphate (OP)
    nerve agents was developed. The basic element of this enzyme electrode was a pH electrode
    modified with an immobilized organophosphorus hydrolase (OPH) layer formed by cross-linking
    OPH ...

  8. Enzyme-linked immunosorbent assay for detection of organophosphorylated butyrylcholinesterase: A biomarker of exposure to organophosphate agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Liming; Du, Dan; Lu, Donglai

    2011-05-05

    A sandwich enzyme-linked immunosorbent assay (sELISA) is developed for detection of organophosphorylated butyrylcholinesterase (OP-BChE), a potential biomarker for human exposure to organophosphate insecticides and nerve agents. A pair of antibodies specific to OP-BChE adduct were identified through systematic screening of several anti BChE antibodies (anti-BChE) and anti-phosphoserine antibodies (anti-Pser) from different sources. The selected anti-BChE (set as capture antibody) antibodies recognize both phosphorylated and nonphosphorylated BChE. These antibodies can therefore be used to capture both BChE and OP-BChE from the sample matrices. The anti- Pser (set as detecting antibody) was used to recognize the OP moiety of OP-BChE adducts. Withmore » the combination of the selected antibody pair, several key parameters (such as the concentration of anti-BChE and anti-Pser, and the blocking agent) were optimized to enhance the sensitivity and selectivity of the sELISA. Under the optimal conditions, the sELISA has shown a wide linear range from 0.03 nM to 30 nM, with a detection limit of 0.03 nM. Furthermore, the sELISA was successfully applied to detect OP-BChE using in-vitro biological samples such as rat plasma spiked with OP-BChE with excellent adduct recovery (z>99 %). These results demonstrate that this novel approach holds great promise to develop an ELISA kit and offers a simple and cost-effective tool for screening/evaluating exposure to organophosphate insecticides and nerve agents.« less

  9. A comprehensive review on experimental and clinical findings in intermediate syndrome caused by organophosphate poisoning

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abdollahi, Mohammad, E-mail: mohammad.abdollahi@utoronto.ca; Karami-Mohajeri, Somayyeh

    2012-02-01

    Acute organophosphate (OP) intoxication is important because of its high morbidity and mortality and occurrence of muscular paralysis associated by inhibition of acetylcholinesterase (AChE) activity at the neuromuscular junction. Cholinergic crisis, intermediate syndrome (IMS), and OP-induced delayed neuropathy (OPIDN) are the evidences that can be observed in OP intoxication. The main cause of morbidity due to OP poisoning is IMS that occurs 24–96 h after poisoning. Mechanisms underlying the IMS are not fully known. Although the electrophysiological aspects of delayed neuropathy are best characterized, the IMS remain very little studied. The aim of this study was to revisit current knowledgemore » related to OP and the IMS. For this purpose, a systematic review without date limitation was performed. A total of 599 relevant articles were found and reviewed. Data were categorized according to experimental and clinical studies. Occurrences of persistent AChE inhibition, electromyography changes, muscle cell injury, and oxidative stress are the most important pieces of evidence for involvement of IMS in OP toxicity. Delayed AChE inhibition, muscle necrosis, down regulation or desensitization of postsynaptic ACh receptors, failure of postsynaptic ACh release, and oxidative stress-related myopathy are involved in IMS. Toxicokinetic factors, such as a high lipid-solubility, duration of AChE inhibition and metabolite excretion, evolution of alterations on repetitive nerve stimulation (RNS), type and frequency of muscle lesions can estimate the probability of the IMS. Plasma AChE of less than 200 units is a predictor and the 30 Hz RNS decremental response could be a useful marker for the IMS.« less

  10. Case histories of organophosphate pesticides killing birds of prey in the United States

    USGS Publications Warehouse

    Henny, C.J.; Kolbe, E.J.; Hill, E.F.; Blus, L.J.

    1985-01-01

    Since 1982 when secondary. poisoning of Red-tailed Hawks (Buteo jamaicensis) was documented following the recommended use of famphur on cattle, the Patuxent Wildlife Research Center has tested for organophosphate (OP) poisoning in selected birds of prey found dead. This report documents the circumstances for a number of. cases where birds of prey were killed by OP pesticides in the United States. Many of the cases were brought to our attention by the U S. Fish and Wildlife Service Division of Law Enforcement The cases may be divided into three categories: misuse, approved use, and unknown. Now that we are looking for OP poisoning of birds of prey, we are finding it more frequently than previously suspected.

  11. NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta

    2007-03-15

    Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects ofmore » both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures.« less

  12. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review.

    PubMed

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2011-09-01

    Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.

  13. Organophosphate esters in East Greenland polar bears and ringed seals: Adipose tissue concentrations and in vitro depletion and metabolite formation.

    PubMed

    Strobel, Adelle; Willmore, William G; Sonne, Christian; Dietz, Rune; Letcher, Robert J

    2018-04-01

    East Greenland is a contamination "hot spot" for long-range transported anthropogenic chemicals, including organophosphate esters (OPEs). High concentrations of OPEs have been reported in arctic air while very little is known for wildlife where OPE tissue residues levels appear to be strongly influenced by biotransformation. In the present study, the hepatic in vitro metabolism of six environmentally relevant organophosphate (OP) triesters and corresponding OP diester formation were investigated in East Greenland polar bears (PBs) and ringed seals (RSs). The in vitro metabolism assay results were compared to adipose levels in field samples from the same individuals. In vitro OP triester metabolism was generally rapid and structure-dependent, where PBs metabolized OPEs more rapidly than RSs. Exceptions were the lack of triethyl phosphate (TEP) metabolism and slow metabolism of tris(2-ethylhexyl) phosphate (TEHP) in both species. OP diester metabolites were also formed with the exception of TEP which was not metabolized at all. Tris(1,3-dichloro-2-propyl) phosphate was completely converted to its corresponding diester. However, the mass balances showed that OP diester formation corresponding to TEHP, tri(n-butyl) phosphate, and tris(2-butyoxyethyl) phosphate did not account for 100% of the OP triester depletion, which indicated alternate pathways of OP triester metabolism had occurred. Triphenyl phosphate was completely converted to its OP diester metabolite in PBs but not in RSs suggesting species-specific differences. The results demonstrated that OP triester bioaccumulation and fate in PBs versus their RS prey is substantially influenced by biotransformation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Yonggang; Lein, Pamela J.; Liu, Cuimei

    2012-07-15

    Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylflurophosphate (DFP). Adult male Sprague–Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatmentmore » with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. -- Highlights: ► NRG-1 blocked DFP induced neuronal injury. ► NRG-1 did not protect against seizures in rats exposed to DFP. ► NRG-1 blocked apoptosis and oxidative stress in the brains of DFP-intoxicated rats. ► Administration of NRG-1 at 1 h after DFP injection prevented delayed neuronal injury.« less

  15. AMPEROMETRIC THICK-FILM STRIP ELECTRODES FOR MONITORING ORGANOPHOSPHATE NERVE AGENTS BASED ON IMMOBILIZED ORGANOPHOSPHORUS HYDROLASE. (R823663)

    EPA Science Inventory

    An amperometric biosensor based on the immobilization of organophosphorus hydrolase
    (OPH) onto screen-printed carbon electrodes is shown useful for the rapid, sensitive, and low-cost
    detection of organophosphate (OP) nerve agents. The sensor relies upon the sensitive and ra...

  16. The role of oxidative stress in organophosphate and nerve agent toxicity

    PubMed Central

    Pearson, Jennifer N.; Patel, Manisha

    2016-01-01

    Organophosphate nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent organophosphate toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to organophosphate agents. Key findings of these studies include alterations in mitochondrial function and increased free radical–mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in organophosphate neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of organophosphate-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures. PMID:27371936

  17. Oxidative stress in organophosphate poisoning: role of standard antidotal therapy.

    PubMed

    Vanova, Nela; Pejchal, Jaroslav; Herman, David; Dlabkova, Alzbeta; Jun, Daniel

    2018-08-01

    Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration. Copyright © 2018 John Wiley & Sons, Ltd.

  18. Care of nestlings by wild female starlings exposed to an organophosphate pesticide

    USGS Publications Warehouse

    Grue, C.E.; Powell, G.V.N.; McChesney, M.J.

    1982-01-01

    (1) Our objective was to determine the effect of exposure to an organophosphate pesticide (OP), dicrotophos (3-hydroxy-N,N-dimethyl-cis-scrotonamide dimethyl phosphate), on care of nestlings by wild female starlings (Sturnus vulgaris)....(2) We selected twelve pairs of active nests based on synchrony in the reproductive cycle. When nestlings were 10 days old (day 10), adult males were captured and killed and brood size was adjusted to four. The frequency and temporal distribution of sorties made by each pair of females to feed their young were recorded for 2 h at 18.00 hours on day 11 and 06.00 hours on day 12. One female from each pair was given a single oral dose of dicrotophos (2.5 mg/kg of body weight) dissolved in corn oil; the second female received an equivalent exposure of pure corn oil. Birds were released and their nestlings weighed. Parental care was again monitored between 18.00 and 20.00 hours on day 12 and 06.00 and 08.00 hours on day 13. Females were then captured and they with their young were weighed and killed. Changes in parental care in OP-dosed and control females were compared using paired t-tests. ....(3) The OP-dosed females made significantly (P < 0.5) fewer sorties to feed their young and remained away from their boxes for longer periods of time than controls. Nestlings of OP-treated females lost significantly more weight (X = 9.3%) than nestlings of controls (X = 3.2%). Brain ChE activity in OP-treated females was inhibited an average of 50.7% compared with controls. Weight changes in OP-dosed (X = -8.9%) and control females (X = -8.3%) were similar.....(4) Results indicate that parental care may be significantly reduced in songbirds receiving severe but sublethal exposure to organophosphate pesticides. The potential for a reduction or modification in parental care to alter reproductive success in passerines is discussed..... (5) Techniques utilized, or modifications thereof, may be useful in collecting the additional data needed to

  19. Organophosphate degrading microorganisms and enzymes as biocatalysts in environmental and personal decontamination applications.

    PubMed

    Yair, Simo; Ofer, Butnaro; Arik, Eisenkraft; Shai, Shrot; Yossi, Rosman; Tzvika, Dushnitsky; Amir, Krivoy

    2008-01-01

    One of the major challenges in dealing with chemical warfare agent (CWA) dispersal, whether in the battlefield or after a terror act, is decontamination and rehabilitation of any contaminated area. Organophosphates (OPs) are considered to be among the deadliest CWAs to date. Other OPs are used as pesticides in modern agriculture, and are considered environmentally hazardous. Current methods for OP decontamination are either dangerous or insufficiently effective. As a promising solution for this problem, bioremediation--the use of biocomponents for environmental remediation--is a potentially effective, safe, and environment-friendly method. The technology relies on several enzymatic mechanisms, and can be applied in various ways. We will review recent achievements and potential applications, such as biocatalyst-containing foams and an enzymatic sponge, for environmental as well as personal exterior decontamination.

  20. Current and emerging strategies for organophosphate decontamination: special focus on hyperstable enzymes.

    PubMed

    Jacquet, Pauline; Daudé, David; Bzdrenga, Janek; Masson, Patrick; Elias, Mikael; Chabrière, Eric

    2016-05-01

    Organophosphorus chemicals are highly toxic molecules mainly used as pesticides. Some of them are banned warfare nerve agents. These compounds are covalent inhibitors of acetylcholinesterase, a key enzyme in central and peripheral nervous systems. Numerous approaches, including chemical, physical, and biological decontamination, have been considered for developing decontamination methods against organophosphates (OPs). This work is an overview of both validated and emerging strategies for the protection against OP pollution with special attention to the use of decontaminating enzymes. Considerable efforts have been dedicated during the past decades to the development of efficient OP degrading biocatalysts. Among these, the promising biocatalyst SsoPox isolated from the archaeon Sulfolobus solfataricus is emphasized in the light of recently published results. This hyperthermostable enzyme appears to be particularly attractive for external decontamination purposes with regard to both its catalytic and stability properties.

  1. The effectiveness of an educational intervention to improve knowledge and perceptions for reducing organophosphate pesticide exposure among Indonesian and South Australian migrant farmworkers

    PubMed Central

    Suratman, Suratman; Ross, Kirstin E; Babina, Kateryna; Edwards, John William

    2016-01-01

    Background Farmworkers are at risk of exposure to organophosphate pesticides (OPs). Improvements of knowledge and perceptions about organophosphate (OP) exposure may be of benefit for the reduction in OP exposure. Purpose The purpose of this study was to examine the effectiveness of an educational intervention to improve knowledge and perceptions for reducing OP exposure among Indonesian and South Australian (SA) migrant farmworkers. Methods This was a quasi-experimental study. The educational intervention used a method of group communication for 30 Indonesian farmworkers and individual communication for seven SA migrant farmworkers. Knowledge and perceptions about OP exposure were measured pre-intervention and 3 months after the intervention. Results Unadjusted intervention effects at follow-up showed statistically significantly improved scores of knowledge (both adverse effects of OPs and self-protection from OP exposure), perceived susceptibility, and perceived barriers among Indonesian farmworkers compared with SA migrant farmworkers. Furthermore, these four significant variables in the unadjusted model and the two other variables (perceived severity and perceived benefits) were statistically significant after being adjusted for the level of education and years working as a farmworker. In contrast, knowledge about adverse effects of OPs was the only variable that was statistically significantly improved among SA migrant farmworkers. The results of this study suggests educational interventions using a method of group communication could be more effective than using individual intervention. Conclusion These improvements provide starting points to change health behavior of farmworkers, particularly to reduce OP exposure, both at the workplace and at home. PMID:26855602

  2. Pesticide Use and Self-Reported Symptoms of Acute Pesticide Poisoning among Aquatic Farmers in Phnom Penh, Cambodia.

    PubMed

    Jensen, Hanne Klith; Konradsen, Flemming; Jørs, Erik; Petersen, Jørgen Holm; Dalsgaard, Anders

    2011-01-01

    Organophosphates and carbamates (OPs/CMs) are known for their acetylcholinesterase inhibiting character. A cross-sectional study of pesticide handling practices and self-perceived symptoms of acute pesticide poisoning was conducted using questionnaire-based interviews with 89 pesticide sprayers in Boeung Cheung Ek (BCE) Lake, Phnom Penh, Cambodia. The study showed that 50% of the pesticides used belonged to WHO class I + II and personal protection among the farmers were inadequate. A majority of the farmers (88%) had experienced symptoms of acute pesticide poisoning, and this was significantly associated with the number of hours spent spraying with OPs/CMs (OR = 1.14, CI 95%: 1.02-1.28). The higher educated farmers reduced their risk of poisoning by 55% for each extra personal protective measure they adapted (OR = 0.45, CI 95%: 0.22-0.91). These findings suggest that improving safe pesticide management practices among the farmers and enforcing the effective banning of the most toxic pesticides will considerably reduce the number of acute pesticide poisoning episodes.

  3. The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon.

    PubMed

    Axelrad, J C; Howard, C V; McLean, W G

    2003-03-14

    Speculation about potential neurotoxicity due to chronic exposure to low doses of organophosphate (OP) pesticides is not yet supported by experimental evidence. The objective of this work was to use a cell culture model of chronic OP exposure to determine if such exposure can alter the sensitivity of nerve cells to subsequent acute exposure to OPs or other compounds. NB2a neuroblastoma cells were grown in the presence of 25 microM diazinon for 8 weeks. The OP was then withdrawn and the cells were induced to differentiate in the presence of various other pesticides or herbicides, including OPs and OP-containing formulations. The resulting outgrowth of neurite-like structures was measured by light microscopy and quantitative image analysis and the IC(50) for each OP or formulation was calculated. The IC(50) values in diazinon-pre-exposed cells were compared with the equivalent values in cells not pre-exposed to diazinon. The IC(50) for inhibition of neurite outgrowth by acute application of diazinon, pyrethrum, glyphosate or a commercial formulation of glyphosate was decreased by between 20 and 90% after pre-treatment with diazinon. In contrast, the IC(50) for pirimiphos methyl was unaffected and those for phosmet or chlorpyrifos were increased by between 1.5- and 3-fold. Treatment of cells with chlorpyrifos or with a second glyphosate-containing formulation led to the formation of abnormal neurite-like structures in diazinon-pre-exposed cells. The data support the view that chronic exposure to an OP may reduce the threshold for toxicity of some, but by no means all, environmental agents.

  4. Early brain magnetic resonance imaging can predict short and long-term outcomes after organophosphate poisoning in a rat model.

    PubMed

    Shrot, Shai; Tauber, Maya; Shiyovich, Arthur; Milk, Nadav; Rosman, Yossi; Eisenkraft, Arik; Kadar, Tamar; Kassirer, Michael; Cohen, Yoram

    2015-05-01

    Magnetic resonance (MR) imaging is a sensitive modality for demonstrating in vivo alterations in brain structure and function after acute organophosphate (OP) poisoning. The goals of this study were to explore early imaging findings in organophosphate-poisoned animals, to assess the efficacy of centrally acting antidotes and to find whether early MR findings can predict post-poisoning cognitive dysfunction. Sprague-Dawley rats were poisoned with the agricultural OP paraoxon and were treated with immediate atropine and obidoxime (ATOX) to reduce acute mortality caused by peripheral inhibition of acetylcholinesterase. Animals were randomly divided into three groups based on the protocol of centrally acting antidotal treatment: group 1 - no central antidotal treatment (n=10); group 2 - treated with midazolam (MID) at 30 min after poisoning (n=9), group 3 - treated with a combination of MID and scopolamine (SCOP) at 30 min after poisoning (n=9) and controls (n=6). Each animal had a brain MR examination 3 and 24 h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel (1)H MR spectroscopy (localized on the thalami, to measure total creatine [Cr], N-acetyl-aspartate [NAA] and cholines [Cho] levels). Eleven days after poisoning each animal underwent a Morris water maze to assess hippocampal learning. Eighteen days after poisoning, animals were euthanized, and their brains were dissected, fixed and processed for histology. All paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3 h after poisoning. Both MID and MID+SCOP prevented most of the cortical edema, with equivalent efficacy. Brain metabolic dysfunction, manifested as decreased NAA/Cr, appeared in all poisoned animals as early as 3h after exposure (1.1 ± 0.07 and 1.42 ± 0.05 in ATOX and control groups, respectively) and remained lower compared to non-poisoned animals even

  5. A High-Throughput Enzyme Assay for Organophosphate Residues in Milk

    PubMed Central

    Mishra, Rupesh K.; Deshpande, Kanchanmala; Bhand, Sunil

    2010-01-01

    A rapid, high-sensitivity, chemiluminescence (CL) enzyme assay for the determination of organophosphate (OP) residues in milk is presented. The assay for quantification of OP residues in milk is based on the inhibition of enzyme butyrylcholinesterase (BuChE). BuChE was stabilized and preloaded in 384 well plates at 30 °C. The assay permits rapid determination of OPs in milk within 12 min including an incubation step. The enzyme assay was tested for individual and mixtures of OPs such as methyl paraoxon (MPOx), methyl parathion (MP) and malathion (MT) in milk to evaluate their synergistic effect on BuChE inhibition. Good linearity was obtained in the range 0.005–50 μg·L−1 for MPOx and 0.5–1,000 μg·L−1 for MP as well as MT in milk. Mean recovery of 93.2%–98.6% was obtained for MPOx spiked milk samples with 0.99%–1.67% reproducibility (RSD). The proposed method facilitated rapid screening of milk samples in 384 well plate formats with further miniaturization presented in 1,536 well plates. PMID:22163525

  6. Cholinesterase Structure: Identification of Mechanisms and Residues Involved in Organophosphate Inhibition and Enzyme Reactivation

    DTIC Science & Technology

    2005-05-01

    nerve agents , soman is the great- terrorist acts. At the same time, OP pesticides , such as est challenge since both the rapid aging of the soman- paraoxon...also from enzyme very slowly (requiring hours, days, or weeks used as nerve warfare agents . Similar to pesticides , nerve for complete dissociation...TERMS acetylcholinesterase, nerve agent antidotes and propylaxis, organophosphate scavenging , oxime reactivation fluorescence spectroscopy, exposure

  7. Differentially expressed genes and pathways induced by organophosphates in human neuroblastoma cells.

    PubMed

    Li, Tianwei; Zhao, Hongtao; Hung, Guo-Chiuan; Han, Jing; Tsai, Shien; Li, Bingjie; Zhang, Jing; Puri, Raj K; Lo, Shyh-Ching

    2012-12-01

    Organophosphates (OPs) are toxic chemicals commonly used as pesticides and herbicides. Some OPs are highly toxic to humans and have been used in warfare and terrorist attacks. In order to elucidate the molecular mechanisms of injury caused by OPs, the differentially expressed genes were analyzed in human SK-N-SH neuroblastoma cells induced by three OPs. The SK-N-SH cells were treated with one of the three OPs, chlorpyrifos, dichlorvos or methamidophos at LC20 (high-dose), the concentration causing 20% cell death, as well as 1/20 of LC20 (low-dose), a sub-lethal concentration with no detectable cell death, for 24 h. The genome-wide gene changes were identified by Agilent Microarray System, and analyzed by microarray analysis tools. The analysis revealed neuroblastoma cells treated with the high doses of all three OPs markedly activated cell apoptosis and inhibited cell growth and proliferation genes, which would most likely lead to the process of cell death. Interestingly, the analysis also revealed significant decrease in expressions of many genes in a specific spliceosome pathway in cells treated with the low doses of all three different OPs. The change of spliceosome pathway may represent an important mechanism of injury in neuronal cells exposed to low doses of various OPs. In addition to unraveling a potentially different form of OP pathogenesis, this finding could provide a new diagnostic marker in assessing OP-associated injury in cells or tissues. In addition, these results could also contribute to the development of new prevention and/or therapeutic regimens against OP toxicity.

  8. Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown, and the unknown.

    PubMed

    Merwin, Samantha J; Obis, Teresa; Nunez, Yanelli; Re, Diane B

    2017-08-01

    Amyotrophic lateral sclerosis (ALS) is the most common adult-onset paralytic disorder. It is characterized by progressive degeneration of the motor neurons controlling voluntary movement. The underlying mechanisms remain elusive, a fact that has precluded development of effective treatments. ALS presents as a sporadic condition 90-95% of the time, i.e., without familial history or obvious genetic mutation. This suggests that ALS has a strong environmental component. Organophosphates (OPs) are prime candidate neurotoxicants in the etiology of ALS, as exposure to OPs was linked to higher ALS incidence among farmers, soccer players, and Gulf War veterans. In addition, polymorphisms in paraoxonase 1, an enzyme that detoxifies OPs, may increase individual vulnerability both to OP poisoning and to the risk of developing ALS. Furthermore, exposure to high doses of OPs can give rise to OP-induced delayed neuropathy (OPIDN), a debilitating condition akin to ALS characterized by similar motor impairment and paralysis. The question we pose in this review is: "what can we learn from acute exposure to high doses of neurotoxicants (OPIDN) that could help our understanding of chronic diseases resulting from potentially decades of silent exposure (ALS)?" The resemblances between OPIDN and ALS are striking at the clinical, etiological, neuropathological, cellular, and potentially molecular levels. Here, we critically present available evidence, discuss current limitations, and posit future research. In the search for the environmental origin of ALS, OPIDN offers an exciting trail to follow, which can hopefully lead to the development of novel strategies to prevent and cure these dreadful disorders.

  9. A Mechanism-based 3D-QSAR Approach for Classification and Prediction of Acetylcholinesterase Inhibitory Potency of Organophosphate and Carbamate Analogs

    EPA Science Inventory

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understandi...

  10. Quantitative structure-toxicity relationship (QSTR) studies on the organophosphate insecticides.

    PubMed

    Can, Alper

    2014-11-04

    Organophosphate insecticides are the most commonly used pesticides in the world. In this study, quantitative structure-toxicity relationship (QSTR) models were derived for estimating the acute oral toxicity of organophosphate insecticides to male rats. The 20 chemicals of the training set and the seven compounds of the external testing set were described by means of using descriptors. Descriptors for lipophilicity, polarity and molecular geometry, as well as quantum chemical descriptors for energy were calculated. Model development to predict toxicity of organophosphate insecticides in different matrices was carried out using multiple linear regression. The model was validated internally and externally. In the present study, QSTR model was used for the first time to understand the inherent relationships between the organophosphate insecticide molecules and their toxicity behavior. Such studies provide mechanistic insight about structure-toxicity relationship and help in the design of less toxic insecticides. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Gas chromatography with pulsed flame photometric detection multiresidue method for organophosphate pesticide and metabolite residues at the parts-per-billion level in representatives commodities of fruits and vegetable crop groups.

    PubMed

    Podhorniak, L V; Negron, J F; Griffith, F D

    2001-01-01

    A gas chromatographic method with a pulsed flame photometric detector (P-FPD) is presented for the analysis of 28 parent organophosphate (OP) pesticides and their OP metabolites. A total of 57 organophosphates were analyzed in 10 representative fruit and vegetable crop groups. The method is based on a judicious selection of known procedures from FDA sources such as the Pesticide Analytical Manual and Laboratory Information Bulletins, combined in a manner to recover the OPs and their metabolite(s) at the part-per-billion (ppb) level. The method uses an acetone extraction with either miniaturized Hydromatrix column partitioning or alternately a miniaturized methylene dichloride liquid-liquid partitioning, followed by solid-phase extraction (SPE) cleanup with graphitized carbon black (GCB) and PSA cartridges. Determination of residues is by programmed temperature capillary column gas chromatography fitted with a P-FPD set in the phosphorus mode. The method is designed so that a set of samples can be prepared in 1 working day for overnight instrumental analysis. The recovery data indicates that a daily column-cutting procedure used in combination with the SPE extract cleanup effectively reduces matrix enhancement at the ppb level for many organophosphates. The OPs most susceptible to elevated recoveries around or greater than 150%, based on peak area calculations, were trichlorfon, phosmet, and the metabolites of dimethoate, fenamiphos, fenthion, and phorate.

  12. Interpreting population estimates of birds following pesticide applications--behavior of male starlings exposed to an organophosphate pesticide

    USGS Publications Warehouse

    Grue, C.E.; Shipley, B.J.; Ralph, C. John; Scott, J. Michael

    1981-01-01

    We determined activity budgets for 10 pairs of captive male Starlings between 7 May and 18 July 1980. Our objective was to quantify changes in behavior after exposure to an organophosphate (OP) pesticide and to assess the impact of changes in behavior on the interpretation of population estimates of birds following pesticide applications. We observed each pair of males for an hour at 07:30 and 09:30 for four days and classified their behavior into one of four categories: flying, perching, foraging, or singing and displaying. At 06:30 on day 2, one male received a single oral dose of 2.5 mg dicrotophos (3-hydroxy-N, N-dimethyl-cis-crotonamide dimethyl phosphate) per kg of body weight; the other male received an equivalent exposure of corn oil. Changes in the activity budgets of OP-dosed and control males were compared using t-tests. Activity of OP-dosed males was significantly (P _ 0.05) reduced within the 2-4 h following exposure. OP-dosed males spent more time perching (46.1%) than controls and less time flying (-96.6%), foraging (-28.5%), and singing and displaying (-49.5%). The frequency of perching (-75.3%), flying (-83.8%), foraging (-54.1%), and singing and displaying (- 59.2%) was significantly reduced. Activity in OP-dosed males returned to normal by 26-28 h posttreatment. Results suggest that movement and vocalization may be significantly reduced in birds exposed to organophosphate and carbamate pesticides. Conventional censusing techniques and population estimating procedures may, therefore, be inadequate to assess changes in bird populations after pesticide applications because of the difficulty in separating decreases in density due to mortality or emigration from reductions in activity.

  13. Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.

    PubMed

    Hondred, John A; Breger, Joyce C; Alves, Nathan J; Trammell, Scott A; Walper, Scott A; Medintz, Igor L; Claussen, Jonathan C

    2018-04-04

    Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors. Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways. The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia. ∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing. The enzyme phosphotriesterase (PTE) was conjugated to the electrode surface via glutaraldehyde cross-linking. The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents. Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples. Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.

  14. Organophosphate-induced intermediate syndrome: aetiology and relationships with myopathy.

    PubMed

    Karalliedde, Lakshman; Baker, David; Marrs, Timothy C

    2006-01-01

    The intermediate syndrome (IMS) following organophosphorus (OP) insecticide poisoning was first described in the mid-1980s. The syndrome described comprised characteristic symptoms and signs occurring after apparent recovery from the acute cholinergic syndrome. As the syndrome occurred after the acute cholinergic syndrome but before organophosphate-induced delayed polyneuropathy, the syndrome was called 'intermediate syndrome'. The IMS occurs in approximately 20% of patients following oral exposure to OP pesticides, with no clear association between the particular OP pesticide involved and the development of the syndrome. It usually becomes established 2-4 days after exposure when the symptoms and signs of the acute cholinergic syndrome (e.g. muscle fasciculations, muscarinic signs) are no longer obvious. The characteristic features of the IMS are weakness of the muscles of respiration (diaphragm, intercostal muscles and accessory muscles including neck muscles) and of proximal limb muscles. Accompanying features often include weakness of muscles innervated by some cranial nerves. It is now emerging that the degree and extent of muscle weakness may vary following the onset of the IMS. Thus, some patients may only have weakness of neck muscles whilst others may have weakness of neck muscles and proximal limb muscles. These patients may not require ventilatory care but close observation and monitoring of respiratory function is mandatory. Management is essentially that of rapidly developing respiratory distress and respiratory failure. Delays in instituting ventilatory care will result in death. Initiation of ventilatory care and maintenance of ventilatory care often requires minimal doses of non-depolarising muscle relaxants. The use of depolarising muscle relaxants such as suxamethonium is contraindicated in OP poisoning. The duration of ventilatory care required by patients may differ considerably and it is usual for patients to need ventilatory support for 7

  15. Children's Contrast Sensitivity Function in Relation to Organophosphate Insecticide Prenatal Exposure in the Mother-Child PELAGIE Cohort.

    PubMed

    Cartier, Chloé; Warembourg, Charline; Monfort, Christine; Rouget, Florence; Limon, Gwendolina; Durand, Gaël; Cordier, Sylvaine; Saint-Amour, Dave; Chevrier, Cécile

    2018-05-24

    Human exposure to organophosphate pesticides (OP) is widespread. Several studies suggest that OP prenatal exposure alters the development of cognitive and behavioural functions in children, but the effects of OP prenatal exposure on child sensory functions are largely unknown. The aim of the study was to evaluate the association between OP prenatal exposure and visual processing in school-aged children from the mother-child PELAGIE cohort (France). OP biomarkers of exposure were measured in maternal urine samples at the beginning of pregnancy. The Functional Acuity Contrast Test (FACT) was used to assess visual contrast sensitivity in 180 children at 6 years of age. Linear regression models were performed on all children, and separately for boys and girls, taking into account various potential confounders, including maternal education and breastfeeding. No associations were observed in the whole sample, while maternal OP urinary metabolite levels were associated with a decrease of FACT scores in boys. These findings indicate that OP prenatal exposure might impair visual processing later in life in boys only. Copyright © 2018. Published by Elsevier B.V.

  16. Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity.

    PubMed

    Kaur, Shamsherjit; Singh, Satinderpal; Chahal, Karan Singh; Prakash, Atish

    2014-11-01

    Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.

  17. Electrochemical Sensor for Organophosphate Pesticides and Nerve Agents Using Zirconia Nanoparticles as Selective Sorbents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Guodong; Lin, Yuehe

    2005-09-15

    Electrochemical sensor for detection of organophosphate (OP) pesticides and nerve agents using zirconia (ZrO₂) nanoparticles as selective sorbents is presented. Zirconia nanoparticles were electrodynamically deposited onto the polycrystalline gold electrode by cyclic voltammetry. Because of a strong affinity of zirconia to the phosphoric group, nitroaromatic OPs strongly bind to the ZrO₂ nanoparticle surface. The electrochemical characterization and anodic stripping voltammetric performance of bound OPs were evaluated using cyclic voltammetric and square-wave voltammetric (SWV) analysis. SWV was used to monitor the amount of bound OPs and provide simple, fast, and facile quantitative methods for nitroaromatic OP compounds. The sensor surface canmore » be regenerated by successively running SWV scanning. Operational parameters, including the amount of nanoparticles, adsorption time, and the pH of the reaction medium have been optimized. The stripping voltammetric response is highly linear over the 5–200 ng/mL (ppb) methyl parathion range examined (2-min adsorption), with a detection limit of 1 ng/mL (10 min accumulation), and good precision (RSD=5.3 %, n = 10). The promising stripping voltammetric performances open new opportunities for fast, simple, and sensitive analyzing of OPs in environmental and biological samples. These findings can lead to a widespread use of electrochemical sensors to detect OP contaminates.« less

  18. Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning.

    PubMed

    Herbert, Julia; Thiermann, Horst; Worek, Franz; Wille, Timo

    2017-08-15

    Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning. Aim of this study was the development of an applicable and easy method to test the therapeutic efficiency of such substances. For this purpose, airway responsiveness in viable precision cut lung slices (PCLS) from rats was analysed. We showed that ACh-induced airway contractions were spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, contractions were irreversible. This effect could be antagonized by addition of the standard therapeutic atropine, thereby presenting a clear indication for treatment efficiency. Now, candidate therapeutic compounds can be evaluated, based on their ability to counteract the irreversible airway contraction in OP poisoned PCLS. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Interaction between organophosphate compounds and cholinergic functions during development.

    PubMed

    Aluigi, M G; Angelini, C; Falugi, C; Fossa, R; Genever, P; Gallus, L; Layer, P G; Prestipino, G; Rakonczay, Z; Sgro, M; Thielecke, H; Trombino, S

    2005-12-15

    Organophosphate (OP) compounds exert inhibition on cholinesterase (ChE) activity by irreversibly binding to the catalytic site of the enzymes. For this reason, they are employed as insecticides for agricultural, gardening and indoor pest control. The biological function of the ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. 3.1.1.7) is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by electrical events, such as intracellular ion concentration changes, as the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which OP exposure may affect human health. The chosen organophosphates were the ones mainly used in Europe: diazinon, chlorpyriphos, malathion, and phentoate, all of them belonging to the thionophosphate chemical class. This research has focused on the comparison between the effects of exposure on the developing embryos at different stages, identifying biomarkers and determining potential risk factors for sensitive subpopulations. The effects of OP oxonisation were not taken into account at this level, because embryonic responses were directly correlated to the changes of AChE activity, as determined by histochemical localisation and biochemical measurements. The identified biomarkers of effect for in vitro experiments were: cell proliferation/apoptosis as well as cell differentiation. For in vivo experiments, the endpoints were: developmental speed, size and shape of pre-gastrula embryos; developmental

  20. Pesticide Use and Self-Reported Symptoms of Acute Pesticide Poisoning among Aquatic Farmers in Phnom Penh, Cambodia

    PubMed Central

    Jensen, Hanne Klith; Konradsen, Flemming; Jørs, Erik; Petersen, Jørgen Holm; Dalsgaard, Anders

    2011-01-01

    Organophosphates and carbamates (OPs/CMs) are known for their acetylcholinesterase inhibiting character. A cross-sectional study of pesticide handling practices and self-perceived symptoms of acute pesticide poisoning was conducted using questionnaire-based interviews with 89 pesticide sprayers in Boeung Cheung Ek (BCE) Lake, Phnom Penh, Cambodia. The study showed that 50% of the pesticides used belonged to WHO class I + II and personal protection among the farmers were inadequate. A majority of the farmers (88%) had experienced symptoms of acute pesticide poisoning, and this was significantly associated with the number of hours spent spraying with OPs/CMs (OR = 1.14, CI 95%: 1.02–1.28). The higher educated farmers reduced their risk of poisoning by 55% for each extra personal protective measure they adapted (OR = 0.45, CI 95%: 0.22–0.91). These findings suggest that improving safe pesticide management practices among the farmers and enforcing the effective banning of the most toxic pesticides will considerably reduce the number of acute pesticide poisoning episodes. PMID:21234245

  1. Bioconcentration and Acute Intoxication of Brazilian Freshwater Fishes by the Methyl Parathion Organophosphate Pesticide

    PubMed Central

    Bosco de Salles, João; Matos Lopes, Renato; de Salles, Cristiane M. C.; Cassano, Vicente P. F.; de Oliveira, Manildo Marcião; Cunha Bastos, Vera L. F.; Bastos, Jayme Cunha

    2015-01-01

    Three species of freshwater Brazilian fishes (pacu, Piaractus mesopotamicus; piavussu, Leporinus macrocephalus, and curimbatá, Prochilodus lineatus) were exposed to an acute dose of 5 ppm methyl parathion organophosphate pesticide. Three to five individuals per species were exposed, one at a time, to 40 liters tap water spiked with Folidol 600. Pesticide concentrations and cholinesterase (ChE) activities were evaluated in serum, liver, brain, heart, and muscle. The bioconcentration of methyl parathion was similar for all studied fishes. Brain tissue showed the highest pesticide concentration, reaching 80 ppm after exposure for 30 min to methyl parathion. Three to 5 hours of 5 ppm methyl parathion exposure provoked the death of all P. lineatus at 92% brain AChE inhibition, whereas fish from the other two species survived for up to 78 hours with less than 80% brain AChE inhibition. Our results indicate that acute toxic effects of methyl parathion to fish are correlated with brain AChE sensitivity to methyl paraoxon. PMID:26339593

  2. Investigating the Molecular Mechanisms of Organophosphate and Pyrethroid Resistance in the Fall Armyworm Spodoptera frugiperda

    PubMed Central

    Carvalho, Renato A.; Omoto, Celso; Field, Linda M.; Williamson, Martin S.; Bass, Chris

    2013-01-01

    The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain) or lambda-cyhalothrin (PYR strain) were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE) and pyrethroid (voltage-gated sodium channel, VGSC) target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS). These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results provide

  3. Investigating the molecular mechanisms of organophosphate and pyrethroid resistance in the fall armyworm Spodoptera frugiperda.

    PubMed

    Carvalho, Renato A; Omoto, Celso; Field, Linda M; Williamson, Martin S; Bass, Chris

    2013-01-01

    The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain) or lambda-cyhalothrin (PYR strain) were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE) and pyrethroid (voltage-gated sodium channel, VGSC) target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS). These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results provide

  4. Functional characterization of carboxylesterase gene mutations involved in Aphis gossypii resistance to organophosphate insecticides.

    PubMed

    Gong, Y-H; Ai, G-M; Li, M; Shi, X-Y; Diao, Q-Y; Gao, X-W

    2017-12-01

    Carboxylesterases (CarEs) play an important role in detoxifying insecticides in insects. Over-expression and structural modification of CarEs have been implicated in the development of organophosphate (OP) insecticide resistance in insects. A previous study identified four nonsynonymous mutations (resulting in four amino acid residue substitutions) in the open reading frame of the carboxylesterase gene of resistant cotton aphids compared to the omethoate susceptible strain, which has possibly influenced the development of resistance to omethoate (a systemic OP insecticide). The current study further characterized the function of these mutations, both alone and in combination, in the hydrolysis of OP insecticides. The metabolism results suggest that the combination of four mutations, mainly existing in the laboratory-selected OP-resistant cotton aphid population, increased the OP hydrolase activity (approximately twofold) at the cost of detectable carboxylesterase activity. The functional studies of single or multiple mutations suggest the positive effect of H104R, A128V and T333P on the acquisition of OP hydrolase activity, especially the combination of H104R with A128V or T333P. K484R substitution decreased both the OP hydrolase activity and the CarE activity, indicating that this mutation primarily drives the negative effect on the acquisition of OP hydrolase activity amongst these four mutations in the resistant strain. The modelling and docking results are basically consistent with the metabolic results, which strongly suggest that the structural gene modification is the molecular basis for the OP resistance in this laboratory-selected cotton aphid strain. © 2017 The Royal Entomological Society.

  5. The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro

    PubMed Central

    Golderman, Valery; Shavit-Stein, Efrat; Tamarin, Ilia; Rosman, Yossi; Shrot, Shai; Rosenberg, Nurit

    2016-01-01

    Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain. PMID:27689805

  6. Effects of acute and repeated oral exposure to the organophosphate insecticide chlorpyrifos on open-field activity in chicks.

    PubMed

    Al-Badrany, Y M A; Mohammad, F K

    2007-11-01

    The effects of the organophosphate insecticide chlorpyrifos on 5min open-field activity were examined in a 7-15 days old chick model. Chlorpyrifos was acutely administered taking into account cholinesterase inhibition and determination of the acute (24h) median lethal dose (LD50). The oral LD50 value of chlorpyrifos in chicks was 18.14mg/kg, with cholinergic toxicosis observed on intoxicated chicks. Chlorpyrifos at the dose rates of 5,10 and 20mg/kg orally produced within 2h signs of cholinergic toxicosis in the chicks and significantly inhibited plasma (40-70%), whole brain (43-69%) and liver (31-46%) cholinesterase activities in a dose-dependent manner. Chlorpyrifos at 2 and 4mg/kg, orally did not produce overt signs of cholinergic toxicosis, but decreased (30, 60 and 90min after dosing) the general locomotor activity of the chicks as seen by a significant increase in the latency to move from the central square of the open-field arena, decreases in the numbers of lines crossed and vocalization score. Repeated daily chlorpyrifos treatments (2 and 4mg/kg, orally) for seven consecutive days also caused hypoactivity in chicks in the open-field behavioral paradigm. Only the high dose of chlorpyrifos (4mg/kg, orally) given repeatedly for 7 days caused significant cholinesterase inhibition in the whole brain (37%) and the liver (22%). In conclusion, chlorpyrifos at single or short-term repeated doses-induced behavioral changes in 7-15 days old chicks, in a model that could be used for further neurobehavioral studies involving subtle effects of organophosphates on chicks.

  7. A novel fluorine-18 β-fluoroethoxy organophosphate positron emission tomography imaging tracer targeted to central nervous system acetylcholinesterase.

    PubMed

    James, Shelly L; Ahmed, S Kaleem; Murphy, Stephanie; Braden, Michael R; Belabassi, Yamina; VanBrocklin, Henry F; Thompson, Charles M; Gerdes, John M

    2014-07-16

    Radiosynthesis of a fluorine-18 labeled organophosphate (OP) inhibitor of acetylcholinesterase (AChE) and subsequent positron emission tomography (PET) imaging using the tracer in the rat central nervous system are reported. The tracer structure, which contains a novel β-fluoroethoxy phosphoester moiety, was designed as an insecticide-chemical nerve agent hybrid to optimize handling and the desired target reactivity. Radiosynthesis of the β-fluoroethoxy tracer is described that utilizes a [(18)F]prosthetic group coupling approach. The imaging utility of the [(18)F]tracer is demonstrated in vivo within rats by the evaluation of its brain penetration and cerebral distribution qualities in the absence and presence of a challenge agent. The tracer effectively penetrates brain and localizes to cerebral regions known to correlate with the expression of the AChE target. Brain pharmacokinetic properties of the tracer are consistent with the formation of an OP-adducted acetylcholinesterase containing the fluoroethoxy tracer group. Based on the initial favorable in vivo qualities found in rat, additional [(18)F]tracer studies are ongoing to exploit the technology to dynamically probe organophosphate mechanisms of action in mammalian live tissues.

  8. Organophosphate pesticides-induced changes in the redox status of rat tissues and protective effects of antioxidant vitamins.

    PubMed

    Mishra, Vibhuti; Srivastava, Nalini

    2015-04-01

    Organophosphates (OPs) pesticides are among the most toxic synthetic chemicals purposefully added in the environment. The common use of OP insecticides in public health and agriculture results in an environmental pollution and a number of acute and chronic poisoning events. Present study was aimed to evaluate the potential of monocrotophos and quinalphos to effect the redox status and glutathione (GSH) homeostasis in rat tissues and find out whether antioxidant vitamins have some protection on the pesticide-induced alterations. The results showed that these pesticides alone or in combination, caused decrease in the levels of GSH and the corresponding increase in the levels of GSSG, decreasing the GSH/GSSG ratio. The results also showed that NADPH/NADP(+) and NADH/NAD(+) ratios were decreased in the liver and brain of rats on exposure with mococrotophos, quinalphos, and their mixture. These pesticides, alone or in combination, caused alterations in the activities of GSH reductase and glucose-6-phosphate dehydrogenase in the rat tissues. However, the expression of the GSH recycling enzymes did not show significant alterations as compared to control. From the results, it can be concluded that these pesticides generate oxidative stress but their effects were not synergistic when given together and prior feeding of antioxidant vitamins tend to reduce the toxicities of these pesticides. Copyright © 2013 Wiley Periodicals, Inc.

  9. Decreasing urinary organophosphate pesticide metabolites among pregnant women and their offspring in Jerusalem: Impact of regulatory restrictions on agricultural organophosphate pesticides use?

    PubMed

    Ein-Mor, Eliana; Ergaz-Shaltiel, Zivanit; Berman, Tamar; Göen, Thomas; Natsheh, Juma; Ben-Chetrit, Avraham; Haimov-Kochman, Ronit; Calderon-Margalit, Ronit

    2018-06-01

    Maternal urinary levels of dialkyl phosphate (DAP) metabolites of organophosphate pesticides (OP) during pregnancy are associated with adverse outcomes in the offspring. Between 2012 and 2014, eighteen active OP ingredients were restricted or banned in Israel for agricultural use. We aimed to study trends of urinary DAP metabolites among pregnant women and their offspring in the era of the new regulations. Pregnant women were recruited at 11-18 weeks of gestation and provided spot urine samples (n = 273). Soon after birth, neonatal urine samples were collected (n = 107). All urine specimens analyzed for DAP metabolites. Trends in DAP metabolites were tested using Mann-Kendall trend statistic (M-K S) and linear regression models were constructed to estimate the association between calendar period and DAP levels between September 2012 and March 2016. Over the study period, median maternal ∑DAP levels decreased from 248 nmol/L to 148 nmol/L. Time of recruitment was associated with a statistically significant decrease in DAP metabolites, which remained significant after multivariate adjustment. Overall, the results for the analysis of before and after June 2014 showed a significant decrease in ∑DAP of -0.198 log10 nmol/L (95%CI: -0.311,-0.084) which corresponds with a decrease of 36.6% in ∑DAP. A similar trend was found for DAP metabolites in neonatal urine. Compared to other studies, pregnant women in Jerusalem had higher ∑DAP levels, even at the end of the study period. We observed significant reductions in maternal and neonatal DAP urinary levels during the period of 2012-2016. Regulations restricting agricultural use of OP seem to be effective in reducing population exposure to OP, in an era when residential use of OP is banned. Copyright © 2018 Elsevier GmbH. All rights reserved.

  10. Organophosphates in aircraft cabin and cockpit air--method development and measurements of contaminants.

    PubMed

    Solbu, Kasper; Daae, Hanne Line; Olsen, Raymond; Thorud, Syvert; Ellingsen, Dag Gunnar; Lindgren, Torsten; Bakke, Berit; Lundanes, Elsa; Molander, Paal

    2011-05-01

    Methods for measurements and the potential for occupational exposure to organophosphates (OPs) originating from turbine and hydraulic oils among flying personnel in the aviation industry are described. Different sampling methods were applied, including active within-day methods for OPs and VOCs, newly developed passive long-term sample methods (deposition of OPs to wipe surface areas and to activated charcoal cloths), and measurements of OPs in high-efficiency particulate air (HEPA) recirculation filters (n = 6). In total, 95 and 72 within-day OP and VOC samples, respectively, have been collected during 47 flights in six different models of turbine jet engine, propeller and helicopter aircrafts (n = 40). In general, the OP air levels from the within-day samples were low. The most relevant OP in this regard originating from turbine and engine oils, tricresyl phosphate (TCP), was detected in only 4% of the samples (min-max OPs, as dibutylphenyl phosphate (DBPP) and tri-n-butyl phosphate (TnBP) originating from hydraulic oils were more prominent in the samples, illustrated by determination of TnBP in all of the within-day samples collected from airplanes (n = 76, min-max 0.02-4.1 µg m(-3)). All samples were collected under normal flight conditions. However, the TCP concentration during ground testing in an airplane that had experienced leakage of turbine oil with subsequent contamination of the cabin and cockpit air, was an order of magnitude higher as compared to after engine replacement (p = 0.02).

  11. Prenatal exposure to organophosphate pesticides and reciprocal social behavior in childhood.

    PubMed

    Furlong, Melissa A; Engel, Stephanie M; Barr, Dana Boyd; Wolff, Mary S

    2014-09-01

    Prenatal exposure to organophosphate pesticides (OPs) has been associated with adverse neurodevelopmental outcomes in childhood, including low IQ, pervasive developmental disorder (PDD), attention problems and ADHD. Many of these disorders involve impairments in social functioning. Thus, we investigated the relationship between biomarkers of prenatal OP exposure and impaired reciprocal social behavior in childhood, as measured by the Social Responsiveness Scale (SRS). Using a multi-ethnic urban prospective cohort of mother-infant pairs in New York City recruited between 1998 and 2002 (n=404) we examined the relation between third trimester maternal urinary levels of dialkylphosphate (ΣDAP) OP metabolites and SRS scores among 136 children who returned for the 7-9year visit. Overall, there was no association between OPs and SRS scores, although in multivariate adjusted models, associations were heterogeneous by race and by sex. Among blacks, each 10-fold increase in total diethylphosphates (ΣDEP) was associated with poorer social responsiveness (β=5.1 points, 95% confidence interval (CI) 0.8, 9.4). There was no association among whites or Hispanics, or for total ΣDAP or total dimethylphosphate (ΣDMP) biomarker levels. Additionally, stratum-specific models supported a stronger negative association among boys for ΣDEPs (β=3.5 points, 95% CI 0.2, 6.8), with no notable association among girls. Our results support an association of prenatal OP exposure with deficits in social functioning among blacks and among boys, although this may be in part reflective of differences in exposure patterns. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Acute poisoning in a child following topical treatment of head lice (pediculosis capitis) with an organophosphate pesticide.

    PubMed

    Hamad, Muddathir H; Adeel, Ahmed Awad; Alhaboob, Ali Abdu N; Ashri, Ahmed M; Salih, Mustafa A

    2016-01-01

    This is a case report of acute organophosphate poisoning in a child treated with topical application of Diazinon-60 (WHO Class II toxicity) for head lice (pediculosis capitis). The patient presented with neurological symptoms and signs. After emergency respiratory and circulatory resuscitation the patient underwent dermal decontamination and was treated with atropine, high flow oxygen and pralidoxime. Scanning electron micrographs of scalp hair specimens revealed both viable and empty head lice nits (lice eggs that attach to the hair shaft). The patient was hospitalized for seven days and discharged after full recovery. The case highlights the importance of raising the awareness of health workers and the community about the danger of misusing pesticides for the treatment of head lice.

  13. Increased Risk of Deep Vein Thrombosis and Pulmonary Thromboembolism in Patients With Organophosphate Intoxication

    PubMed Central

    Lim, Yun-Ping; Lin, Cheng-Li; Hung, Dong-Zong; Ma, Wei-Chih; Lin, Yen-Ning; Kao, Chia-Hung

    2015-01-01

    Abstract Organophosphate (OP) poisoning is a critical cause of morbidity and mortality worldwide. We conducted a nationwide longitudinal cohort study to investigate the development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) among patients admitted with OP intoxication. We identified patients with OP intoxication by using the Taiwan National Health Insurance Research Database and enrolled 9223 patients who were hospitalized for OP intoxication between 2000 and 2011. OP intoxication was diagnosed based on a clinical assessment and serum acetylcholinesterase levels at the time of hospital admission. Each patient in the OP intoxication cohort was randomly frequency matched with 4 patients without OP intoxication based on their age, sex, and index year (36,892 patients as control cohort), and all patients were observed from the index date until the appearance of a DVT or a PTE event, or until December 31, 2011. We analyzed the risks of DVT and PTE by using Cox proportional hazards regression models that included the demographic variables of sex, age, and comorbidities (eg, hypertension, diabetes, cerebral vascular disease, heart failure, all cancer types, and lower leg fracture or surgery). The results revealed a significantly increased risk of developing DVT among patients with OP poisoning (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.03–2.34) but not PTE (adjusted HR = 1.44; 95% CI = 0.83–2.52). Among the patients without comorbidities, the OP poisoning patients compared with controls had a higher adjusted HR of 2.12 (95% CI = 1.21–3.71) for DVT. The results of this nationwide cohort study indicate that the risk of developing DVT is markedly higher in patients with OP intoxication compared with that of the general population. PMID:25569651

  14. Reduction in urinary organophosphate pesticide metabolites in adults after a week-long organic diet.

    PubMed

    Oates, Liza; Cohen, Marc; Braun, Lesley; Schembri, Adrian; Taskova, Rilka

    2014-07-01

    Conventional food production commonly uses organophosphate (OP) pesticides, which can have negative health effects, while organic food is deemed healthier because it is produced without these pesticides. Studies suggest that organic food consumption may significantly reduce OP pesticide exposure in children who have relatively higher pesticide exposure than adults due to their different diets, body weight, behaviour and less efficient metabolism. A prospective, randomised, crossover study was conducted to determine if an organic food diet reduces organophosphate exposure in adults. Thirteen participants were randomly allocated to consume a diet of at least 80% organic or conventional food for 7 days and then crossed over to the alternate diet. Urinary levels of six dialkylphosphate metabolites were analysed in first-morning voids collected on day 8 of each phase using GC-MS/MS with detection limits of 0.11-0.51 μg/L. The mean total DAP results in the organic phase were 89% lower than in the conventional phase (M=0.032 [SD=0.038] and 0.294 [SD=0.435] respectively, p=0.013). For total dimethyl DAPs there was a 96% reduction (M=0.011 [SD=0.023] and 0.252 [SD=0.403] respectively, p=0.005). Mean total diethyl DAP levels in the organic phase were half those of the conventional phase (M=0.021 [SD=0.020] and 0.042 [SD=0.038] respectively), yet the wide variability and small sample size meant the difference was not statistically significant. The consumption of an organic diet for one week significantly reduced OP pesticide exposure in adults. Larger scale studies in different populations are required to confirm these findings and investigate their clinical relevance. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Exposure to airborne organophosphates originating from hydraulic and turbine oils among aviation technicians and loaders.

    PubMed

    Solbu, Kasper; Daae, Hanne Line; Thorud, Syvert; Ellingsen, Dag Gunnar; Lundanes, Elsa; Molander, Paal

    2010-12-01

    This study describes the potential for occupational exposure to organophosphates (OPs) originating from turbine and hydraulic oils, among ground personnel within the aviation industry. The OPs tri-n-butyl phosphate (TnBP), dibutyl phenyl phosphate (DBPP), triphenyl phosphate (TPP) and tricresyl phosphate (TCP) have been emphasized due to their use in such oils. Oil aerosol/vapor and total volatile organic compounds (tVOCs) in air were also determined. In total, 228 and 182 OPs and oil aerosol/vapor samples from technician and loader work tasks during work on 42 and 21 aircrafts, respectively, were collected in pairs. In general, the measured exposure levels were below the limit of quantification (LOQ) for 84%/98% (oil aerosol) and 82%/90% (TCP) of the samples collected during technician/loader work tasks. The air concentration ranges for all samples related to technician work were OPs) mg m(-3), with the highest OP exposure levels measured during wheel well maintenance. For loader work the corresponding air concentration ranges were OPs) mg m(-3), with the highest exposure levels measured during loading from jet engine aircrafts. Investigation of provoked exposure situations revealed substantially higher exposure levels of the contaminants when compared to regular conditions, illustrated by oil aerosol and TCP concentrations up to 240 and 31 mg m(-3), respectively. The tailored OP and the general oil aerosol sampling methods were compared, displaying the advantages of tailored OP sampling for such exposure assessments.

  16. Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: The CHAMACOS cohort.

    PubMed

    Stein, Lauren J; Gunier, Robert B; Harley, Kim; Kogut, Katherine; Bradman, Asa; Eskenazi, Brenda

    2016-09-01

    Previous studies have observed an adverse association between prenatal exposure to organophosphate pesticide (OPs) and child cognition, but few studies consider the potential role of social stressors in modifying this relationship. We seek to explore the potential role of early social adversities in modifying the relationship between OPs and child IQ in an agricultural Mexican American population. Participants from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a prospective longitudinal pre-birth cohort study, include 329 singleton infants and their mothers followed from pregnancy through age 7. Dialkyl phosphate metabolite concentrations (DAPs), a biomarker of organophosphate pesticide exposure, were measured in maternal urine collected twice during pregnancy and averaged. Child cognitive ability was assessed at 7 years using the Wechsler Intelligence Scale for Children - Fourth Edition. Demographic characteristics and adversity information were collected during interviews and home visits at numerous time points from pregnancy until age 7. Among low-income Latina mothers and their children in the Salinas Valley, total adversity and specific domains of adversity including poor learning environment and adverse parent-child relationships were negatively associated with child cognition. Adverse associations between DAP concentrations and IQ were stronger in children experiencing greater adversity; these associations varied by child sex. For example, the association between prenatal OP exposure and Full-Scale IQ is potentiated among boys who experienced high adversity in the learning environment (β=-13.3; p-value <0.01). Greater total and domain-specific adversity modifies negative relationships between prenatal OP exposure and child IQ differently among male and female children. These findings emphasize the need to consider plausible interactive pathways between social adversities and environmental exposures. Copyright

  17. Peripheral Nervous System Function and Organophosphate Pesticide Use among Licensed Pesticide Applicators in the Agricultural Health Study

    PubMed Central

    Starks, Sarah E.; Hoppin, Jane A.; Kamel, Freya; Lynch, Charles F.; Jones, Michael P.; Alavanja, Michael C.; Sandler, Dale P.

    2012-01-01

    Background: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function. Objective: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS). Methods: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates. Results: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold. Conclusions: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators. PMID:22262687

  18. Application of pristine and doped SnO2 nanoparticles as a matrix for agro-hazardous material (organophosphate) detection

    NASA Astrophysics Data System (ADS)

    Khan, Naushad; Athar, Taimur; Fouad, H.; Umar, Ahmad; Ansari, Z. A.; Ansari, S. G.

    2017-02-01

    With an increasing focus on applied research, series of single/composite materials are being investigated for device development to detect several hazardous, dangerous, and toxic molecules. Here, we report a preliminary attempt of an electrochemical sensor fabricated using pristine Ni and Cr-doped nano tin oxide material (SnO2) as a tool to detect agro-hazardous material, i.e. Organophosphate (OP, chlorpyrifos). The nanomaterial was synthesized using the solution method. Nickel and chromium were used as dopant during synthesis. The synthesized material was calcined at 1000 °C and characterized for morphological, structural, and elemental analysis that showed the formation of agglomerated nanosized particles of crystalline nature. Screen-printed films of powder obtained were used as a matrix for working electrodes in a cyclic voltammogram (CV) at various concentrations of organophosphates (0.01 to 100 ppm). The CV curves were obtained before and after the immobilization of acetylcholinesterase (AChE) on the nanomaterial matrix. An interference study was also conducted with hydroquinone to ascertain the selectivity. The preliminary study indicated that such material can be used as suitable matrix for a device that can easily detect OP to a level of 10 ppb and thus contributes to progress in terms of desired device technology for the food and agricultural-industries.

  19. THE MUSCARINIC ANTAGONIST SCOPOLAMINE ATTENUATES CHLORPYRIFOS INDUCED HYPOTHERMIA IN THE DEVELOPING RAT.

    EPA Science Inventory

    Chlorpyrifos (CHP), an anticholinesterase organophosphate (OP) pesticide, induces acute hypothermia in adult and developing rats. Previously we demonstrated that thermoregulation in preweanling pups is markedly more sensitive to the neurotoxic effects of CHP than in adults. The c...

  20. Effects of organophosphates on the regulation of mesenchymal stem cell proliferation and differentiation.

    PubMed

    Prugh, Amber M; Cole, Stephanie D; Glaros, Trevor; Angelini, Daniel J

    2017-03-25

    Mesenchymal stem cells (MSCs) are multipotent cells located within various adult tissues. Recent literature has reported that human bone marrow-derived MSCs express active acetylcholinesterase (AChE) and that disruption of AChE activity by organophosphate (OP) chemicals decreases the ability of MSCs to differentiate into osteoblasts. The potential role of AChE in regulating MSC proliferation and differentiation is currently unknown. In the present study, we demonstrate that MSCs exposed to OPs have both decreased AChE activity and abundance. In addition, exposure to these OPs induced cellular death while decreasing cellular proliferation. Exposures to these compounds also reduced the adipogenic/osteogenic differentiation potentials of the MSCs. To elucidate the possible role of AChE in MSCs signaling following OP exposure, we captured potential AChE binding partners by performing polyhistidine (His 8 )-tagged AChE pulldowns, followed by protein identification using liquid chromatography mass spectrometry (LC-MS). Using this method, we determined that the focal adhesion protein, vinculin, is a potential binding partner with AChE in MSCs and these initial findings were confirmed with follow-up co-immunoprecipitation experiments. Identifying AChE binding partners helps to determine potential pathways associated with MSC proliferation and differentiation, and this understanding could lead to the development of future MSC-based tissue repair therapies. Published by Elsevier B.V.

  1. Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: a systematic review.

    PubMed

    Muñoz-Quezada, María Teresa; Lucero, Boris A; Barr, Dana B; Steenland, Kyle; Levy, Karen; Ryan, P Barry; Iglesias, Veronica; Alvarado, Sergio; Concha, Carlos; Rojas, Evelyn; Vega, Catalina

    2013-12-01

    Many studies have investigated the neurodevelopmental effects of prenatal and early childhood exposures to organophosphate (OP) pesticides among children, but they have not been collectively evaluated. The aim of the present article is to synthesize reported evidence over the last decade on OP exposure and neurodevelopmental effects in children. The Data Sources were PubMed, Web of Science, EBSCO, SciVerse Scopus, SpringerLink, SciELO and DOAJ. The eligibility criteria considered were studies assessing exposure to OP pesticides and neurodevelopmental effects in children from birth to 18 years of age, published between 2002 and 2012 in English or Spanish. Twenty-seven articles met the eligibility criteria. Studies were rated for evidential consideration as high, intermediate, or low based upon the study design, number of participants, exposure measurement, and neurodevelopmental measures. All but one of the 27 studies evaluated showed some negative effects of pesticides on neurobehavioral development. A positive dose-response relationship between OP exposure and neurodevelopmental outcomes was found in all but one of the 12 studies that assessed dose-response. In the ten longitudinal studies that assessed prenatal exposure to OPs, cognitive deficits (related to working memory) were found in children at age 7 years, behavioral deficits (related to attention) seen mainly in toddlers, and motor deficits (abnormal reflexes) seen mainly in neonates. No meta-analysis was possible due to different measurements of exposure assessment and outcomes. Eleven studies (all longitudinal) were rated high, 14 studies were rated intermediate, and two studies were rated low. Evidence of neurological deficits associated with exposure to OP pesticides in children is growing. The studies reviewed collectively support the hypothesis that exposure to OP pesticides induces neurotoxic effects. Further research is needed to understand effects associated with exposure in critical windows of

  2. Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: A systematic review

    PubMed Central

    Muñoz-Quezada, María Teresa; Lucero, Boris A.; Barr, Dana B.; Steenland, Kyle; Levy, Karen; Ryan, P. Barry; Iglesias, Veronica; Alvarado, Sergio; Concha, Carlos; Rojas, Evelyn; Vega, Catalina

    2013-01-01

    Many studies have investigated the neurodevelopmental effects of prenatal and early childhood exposures to organophosphate (OP) pesticides among children, but they have not been collectively evaluated. The aim of the present article is to synthesize reported evidence over the last decade on OP exposure and neurodevelopmental effects in children. The Data Sources were PubMed, Web of Science, EBSCO, SciVerse Scopus, SpringerLink, SciELO and DOAJ. The eligibility criteria considered were studies assessing exposure to OP pesticides and neurodevelopmental effects in children from birth to 18 years of age, published between 2002 and 2012 in English or Spanish. Twenty-seven articles met the eligibility criteria. Studies were rated for evidential consideration as high, intermediate, or low based upon the study design, number of participants, exposure measurement, and neurodevelopmental measures. All but one of the 27 studies evaluated showed some negative effects of pesticides on neurobehavioral development. A positive dose–response relationship between OP exposure and neurodevelopmental outcomes was found in all but one of the 12 studies that assessed dose–response. In the ten longitudinal studies that assessed prenatal exposure to OPs, cognitive deficits (related to working memory) were found in children at age 7 years, behavioral deficits (related to attention) seen mainly in toddlers, and motor deficits (abnormal reflexes) seen mainly in neonates. No meta-analysis was possible due to different measurements of exposure assessment and outcomes. Eleven studies (all longitudinal) were rated high, 14 studies were rated intermediate, and two studies were rated low. Evidence of neurological deficits associated with exposure to OP pesticides in children is growing. The studies reviewed collectively support the hypothesis that exposure to OP pesticides induces neurotoxic effects. Further research is needed to understand effects associated with exposure in critical windows

  3. Oxidation of selected organophosphate pesticides during chlorination of simulated drinking water.

    PubMed

    Kamel, Alaa; Byrne, Christian; Vigo, Craig; Ferrario, Joseph; Stafford, Charles; Verdin, Gregory; Siegelman, Frederic; Knizner, Steven; Hetrick, James

    2009-02-01

    Ten organophosphate (OP) pesticides: phorate, disulfoton, terbufos, methidathion, bensulide, chlorethoxyfos, phosmet, methyl parathion, phostebupirim, and temephos were evaluated for their potential to undergo oxidation to their respective oxons and/or other oxidation analogues in laboratory water. Samples were collected at time intervals up to 72h of chlorination and analyzed by both gas chromatography-mass selective detection (GC-MSD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results show that methidathion and methyl parathion were stable in unchlorinated water, while all other OP pesticides were not stable over the 72h exposure period. In chlorinated water, phorate and disulfoton formed stable sulfone oxons. Temephos formed stable dioxon sulfoxide and dioxon sulfone. Methidathion, bensulide, chlorethyoxyfos, methyl parathion, and phostebupirim formed stable oxons over the 72h exposure period. Terbufos, phorate, disulfoton and temephos oxon sulfoxides; temephos sulfoxide; and phosmet oxon were initially formed but were not detected after 24h. The data illustrate that organothiophosphate pesticides may form oxons and/or other oxidation analogues during chlorination in water treatment plants, which are persistent for at least 72h.

  4. From the Cover: Magnetic Resonance Imaging Reveals Progressive Brain Injury in Rats Acutely Intoxicated With Diisopropylfluorophosphate

    PubMed Central

    Hobson, Brad A.; Sisó, Sílvia; Rowland, Douglas J.; Harvey, Danielle J.; Bruun, Donald A.; Garbow, Joel R.

    2017-01-01

    Abstract Acute intoxication with organophosphates (OPs) can trigger seizures that progress to status epilepticus, and survivors often exhibit chronic neuropathology, cognitive impairment, affective disorders, and/or electroencephalographic abnormalities. Understanding how acute injury transitions to persistent neurological sequelae is critical to developing medical countermeasures for mitigating damage following OP-induced seizures. Here, we used in vivo magnetic resonance imaging (MRI) to monitor the spatiotemporal patterns of neuropathology for 1 month after acute intoxication with diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats administered pyridostigmine bromide (0.1 mg/kg, im) 30 min prior to successive administration of DFP (4 mg/kg, sc), atropine sulfate (2 mg/kg, im), and 2-pralidoxime (25 mg/kg, im) exhibited moderate-to-severe seizure behavior. T2-weighted and diffusion-weighted MR imaging prior to DFP exposure and at 3, 7, 14, 21, or 28 days postexposure revealed prominent lesions, tissue atrophy, and ventricular enlargement in discrete brain regions. Lesions varied in intensity and/or extent over time, with the overall magnitude of injury strongly influenced by seizure severity. Importantly, lesions detected by MRI correlated spatially and temporally with histological evidence of brain pathology. Analysis of histogram parameters extracted from frequency distributions of regional apparent diffusion coefficient (ADC) values identified the standard deviation and 90th percentile of the ADC as robust metrics for quantifying persistent and progressive neuropathological changes. The interanimal and interregional variations observed in lesion severity and progression, coupled with potential reinjury following spontaneous recurrent seizures, underscore the advantages of using in vivo imaging to longitudinally monitor neuropathology and, ultimately, therapeutic response, following acute OP intoxication. PMID:28329842

  5. Impact of environmental temperatures on resistance to organophosphate insecticides in Aedes aegypti from Trinidad.

    PubMed

    Polson, Karen A; Brogdon, William G; Rawlins, Samuel C; Chadee, Dave D

    2012-07-01

    To examine the effects of increasing larval rearing temperatures on the resistance status of Trinidadian populations of Aedes aegypti to organophosphate (OP) insecticides. In 2007-2008, bioassays and biochemical assays were conducted on A. aegypti larvae collected in 2006 from eight geographically distinct areas in Trinidad (Trinidad and Tobago). Larval populations were reared at four temperatures (28 ± 2ºC, 32ºC, 34ºC, and 36ºC) prior to bioassays with OP insecticides (fenthion, malathion, and temephos) and biochemical assays for esterase enzymes. Most larval populations reared at 28 ± 2ºC were susceptible to fenthion (>98% mortality) but resistant to malathion and temephos (< 80% mortality). A positive association was found between resistance to OP insecticides and increased activities of α- and β-esterases in larval populations reared at 28 ± 2ºC. Although larval populations reared at higher temperatures showed variations in resistance to OPs, there was a general increase in susceptibility. However, increases or decreases in activity levels of enzymes did not always correspond with an increase or decrease in the proportion of resistant individuals reared at higher temperatures. Although global warming may cause an increase in dengue transmission, based on the current results, the use of insecticides for dengue prevention and control may yet be effective if temperatures increase as projected.

  6. Ecotoxicity of two organophosphate pesticides chlorpyrifos and dichlorvos on non-targeting cyanobacteria Microcystis wesenbergii.

    PubMed

    Sun, Kai-Feng; Xu, Xiang-Rong; Duan, Shun-Shan; Wang, You-Shao; Cheng, Hao; Zhang, Zai-Wang; Zhou, Guang-Jie; Hong, Yi-Guo

    2015-10-01

    Organophosphate pesticides (OPs), as a replacement for the organochlorine pesticides, are generally considered non-toxic to plants and algae. Chlorpyrifos and dichlorvos are two OPs used for pest control all over the world. In this study, the dose-response of cyanobacteria Microcystis wesenbergii on OPs exposure and the stimulating effect of OPs with and without phosphorus source were investigated. The results showed that high concentrations of chlorpyrifos and dichlorvos caused significant decrease of chlorophyll a content. The median inhibitory concentrations (EC50) of chlorpyrifos and dichlorvos at 96 h were 15.40 and 261.16 μmol L(-1), respectively. Growth of M. wesenbergii under low concentration of OPs (ranged from 1/10,000 to 1/20 EC50), was increased by 35.85 % (chlorpyrifos) and 41.83 % (dichlorvos) at 120 h, respectively. Correspondingly, the highest enhancement on the maximum quantum yield (F v/F m) was 4.20 % (24 h) and 9.70 % (48 h), respectively. Chlorophyll fluorescence kinetics, known as O-J-I-P transients, showed significant enhancements in the O-J, J-I, and I-P transients under low concentrations of dichlorvos at 144 h, while enhancements of chlorophyll fluorescence kinetics induced by low concentrations of chlorpyrifos were only observed in the J-I transient at 144 h. Significant decreases of chlorophyll content, F v/F m and O-J-I-P transients with OPs as sole phosphorus source were found when they were compared with inorganic phosphate treatments. The results demonstrated an evidently hormetic dose-response of M. wesenbergii to both chlorpyrifos and dichlorvos, where high dose (far beyond environmental concentrations) exposure caused growth inhibition and low dose exposure induced enhancement on physiological processes. The stimulating effect of two OPs on growth of M. wesenbergii was negligible under phosphate limitation.

  7. Functional Consequences of Repeated Organophosphate Exposure: Potential Non-Cholinergic Mechanisms

    PubMed Central

    Terry, A.V.

    2012-01-01

    The class of chemicals known as the “organophosphates” (OPs) comprises many of the most common agricultural and commercial pesticides that are used worldwide as well as the highly toxic chemical warfare agents. The mechanism of the acute toxicity of OPs in both target and non-target organisms is primarily attributed to inhibitory actions on various forms of cholinesterase leading to excessive peripheral and central cholinergic activity. However, there is now substantial evidence that this canonical (cholinesterase-based) mechanism cannot alone account for the wide-variety of adverse consequences of OP exposure that have been described, especially those associated with repeated exposures to levels that produce no overt signs of acute toxicity. This type of exposure has been associated with prolonged impairments in attention, memory, and other domains of cognition, as well as chronic illnesses where these symptoms are manifested (e.g., Gulf War Illness, Alzheimer’s disease). Due to their highly reactive nature, it is not surprising that OPs might alter the function of a number of enzymes and proteins (in addition to cholinesterase). However, the wide variety of long-term neuropsychiatric symptoms that have been associated with OPs suggests that some basic or fundamental neuronal process was adversely affected during the exposure period. The purpose of this review is to discuss several non-cholinesterase targets of OPs that might affect such fundamental processes and includes cytoskeletal and motor proteins involved in axonal transport, neurotrophins and their receptors, and mitochondria (especially their morphology and movement in axons). Potential therapeutic implications of these OP interactions are also discussed. PMID:22465060

  8. Au-TiO2/Chit modified sensor for electrochemical detection of trace organophosphates insecticides.

    PubMed

    Qu, Yunhe; Min, Hong; Wei, Yinyin; Xiao, Fei; Shi, Guoyue; Li, Xiaohua; Jin, Litong

    2008-08-15

    In this paper, Au-TiO2/Chit modified electrode was prepared with Au-TiO2 nanocomposite (Au-TiO2) and Chitosan (Chit) as a conjunct. The Au-TiO2 nanocomposite and the films were characterized by electrochemical and spectroscopy methods. A set of experimental conditions was also optimized for the film's fabrication. The electrochemical and electrocatalytic behaviors of Au-TiO2/Chit modified electrode to trace organophosphates (OPs) insecticides such as parathion were discussed in this work. By differential pulse voltammetry (DPV) measurement, the current responses of Au-TiO2/Chit modified electrode were linear with parathion concentration ranging from 1.0 ng/ml to 7.0 x 10(3)ng/ml with the detection limit of 0.5 ng/ml. In order to evaluate the performance of the detection system, we also examined the real samples successfully in this work. It exhibited a sensitive, rapid and easy-to-use method for the fast determination of trace OPs insecticides.

  9. Distribution of PON1 polymorphisms PON1Q192R and PON1L55M among Chinese, Malay and Indian males in Singapore and possible susceptibility to organophosphate exposure.

    PubMed

    Chia, Sin Eng; Mohamed Ali, Safiyya; Yap, Peng Huat Eric; Gan, Linda; Ong, Yeong Bing; Chia, Kee Seng

    2009-03-01

    Organophosphate (OP)-containing pesticides are widely used worldwide for domestic and industrial purposes. Studies on acute and chronic exposure to OPs have revealed numerous health effects attributed mainly to acetylcholinesterase (AChE) inhibition. The enzyme human serum paraoxonase (PON1) is involved in the detoxification of OP compounds. PON1 polymorphisms have been shown to affect susceptibility to OP exposure. We studied the effect of OP exposure on pest control workers and assessed the distribution of two common PON1 polymorphisms in our local population. The exposed group consisted of 103 workers from various pest control companies under the Singapore Pest Management Association while the 91 unexposed workers were from a lead stabilizer factory. For all workers, the mean age was 36.9 (20-70) years and the ethnic distribution was 38.1% Chinese, 44.3% Malay and 17.5% Indian. The mean+/-S.D. exposure duration among the pesticide workers was 10.4+/-8.4 years. The mean+/-S.D. RBC cholinesterase level was 18436.2+/-2078U/L and 18079.6+/-1576U/L for the exposed and unexposed groups, respectively (p=0.216). The mean+/-S.D. serum pseudocholinesterase was 11028.4+/-2867.4U/L and 9433.6+/-2022.6U/L in the exposed and unexposed groups, respectively (p<0.0001). Mean paraoxonase activity was similar among Chinese and Malays (266.5 and 266.3U/L, respectively) whereas that of the Indians was significantly lower (165.6U/L). Our study showed that cholinesterase levels among the exposed were not lower than those in the unexposed group. PON1 polymorphisms differed among ethnic groups, implying that ethnicity could be an important surrogate for identifying susceptible groups in case of OP exposure. Although OP poisoning is rare among occupationally exposed workers in Singapore, this information is useful for other developing countries that have large populations of Chinese, Malays and Indians where OP exposure could be very high especially in agricultural settings.

  10. Prenatal Exposure to Organophosphate Pesticides and Neurobehavioral Development of Neonates: A Birth Cohort Study in Shenyang, China

    PubMed Central

    Zhang, Ying; Han, Song; Liang, Duohong; Shi, Xinzhu; Wang, Fengzhi; Liu, Wei; Zhang, Li; Chen, Lixin; Gu, Yingzi; Tian, Ying

    2014-01-01

    Background A large amount of organophosphate pesticides (OPs) are used in agriculture in China every year, contributing to exposure of OPs through dietary consumption among the general population. However, the level of exposure to OPs in China is still uncertain. Objective To investigate the effect of the exposure to OPs on the neonatal neurodevelopment during pregnancy in Shenyang, China. Methods 249 pregnant women enrolled in the Central Hospital Affiliated to Shenyang Medical College from February 2011 to August 2012. A cohort of the mothers and their neonates participated in the study and information on each subject was obtained by questionnaire. Dialkyl phosphate (DAP) metabolites were detected in the urine of mothers during pregnancy to evaluate the exposure level to OPs. Neonate neurobehavioral developmental levels were assessed according to the standards of the Neonatal Behavioral Neurological Assessment (NBNA). Multiple linear regressions were utilized to analyze the association between pregnancy exposure to OPs and neonatal neurobehavioral development. Results The geometric means (GM) of urinary metabolites for dimethyl phosphate (DMP), dimethyl thiophosphate (DMTP), diethyl phosphate (DEP), and diethyl thiophosphate (DETP) in pregnant women were 18.03, 8.53, 7.14, and 5.64 µg/L, respectively. Results from multiple linear regressions showed that prenatal OP exposure was one of the most important factors affecting NBNA scores. Prenatal total DAP concentrations were inversely associated with scores on the NBNA scales.?Additionally, a 10-fold increase in DAP concentrations was associated with a decrease of 1.78 regarding the Summary NBNA (95% CI, −2.12 to −1.45). And there was an estimated 2.11-point difference in summary NBNA scores between neonates in the highest quintile of prenatal OP exposure and the lowest quintile group. Conclusion The high exposure of pregnant women to OPs in Shenyang, China was the predominant risk factor for neonatal

  11. Sensitivity of nestling and adult starlings to dicrotophos, an organophosphate pesticide

    USGS Publications Warehouse

    Grue, C.E.; Shipley, B.K.

    1984-01-01

    The 24-hr median lethal dose (LD50) of dicrotophos (3-hydroxy-N,N-dimethyl-cis-crotonamide dimethyl phosphate) for free-living 5-day-old nestling European starlings (Sturnus vulgaris, LDso = 4.92 mg/kg body wt) was about one-half that obtained for free-living 15day-old nestlings (9.59 mg/kg) and captive adult males (8.37 mg/kg) and females (8.47 mg/ kg). Nestlings and adults with low pretreatment body weights appeared to be more vulnerable to organophosphate (OP) exposure. Brain cholinesterase (ChE) activity was severely depressed in all birds that died (74-94%); the degree of inhibition did not vary with age or sex. Inhibition of brain ChE in 5-day-old nestlings alive 24 hr post dose (X = 28-43%) was lower than that of 15-day-old (X = 55-68%) and adult (X = 55-77%) survivors. Body weights of OP-dosed birds that died were depressed an average of 20 to 46% in 5-day-olds, 7 to 20% in 15-day-olds, and 0 to 10% in adults; weight losses varied inversely with age and dosage, and directly with time to death. Average weight losses in 5- and 15-day-old survivors (X < 31 and 26%, respectively) varied directly with dose and exceeded comparable values for adults (X = 3-15%). Results suggest that (1) young nestling songbirds may be nearly twice as sensitive as adults to OPs, (2) growth of nestlings may be severely depressed following OP exposure, and (3) recovery of brain ChE activity following exposure to ChE inhibitors may be more rapid in nestlings than adults.

  12. Effect of E-waste Recycling on Urinary Metabolites of Organophosphate Flame Retardants and Plasticizers and Their Association with Oxidative Stress.

    PubMed

    Lu, Shao-You; Li, Yan-Xi; Zhang, Tao; Cai, Dan; Ruan, Ju-Jun; Huang, Ming-Zhi; Wang, Lei; Zhang, Jian-Qing; Qiu, Rong-Liang

    2017-02-21

    In this study, three chlorinated (Cl-mOPs) and five nonchlorinated (NCl-mOPs) organophosphate metabolites were determined in urine samples collected from participants living in an electronic waste (e-waste) dismantling area (n = 175) and two reference areas (rural, n = 29 and urban, n = 17) in southern China. Bis(2-chloroethyl) phosphate [BCEP, geometric mean (GM): 0.72 ng/mL] was the most abundant Cl-mOP, and diphenyl phosphate (DPHP, 0.55 ng/mL) was the most abundant NCl-mOP. The GM concentrations of mOPs in the e-waste dismantling sites were higher than those in the rural control site. These differences were significant for BCEP (p < 0.05) and DPHP (p < 0.01). Results suggested that e-waste dismantling activities contributed to human exposure to OPs. In the e-waste sites, the urinary concentrations of bis(2-chloro-isopropyl) phosphate (r = 0.484, p < 0.01), BCEP (r = 0.504, p < 0.01), dibutyl phosphate (r = 0.214, p < 0.05), and DPHP (r = 0.440, p < 0.01) were significantly increased as the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative stress, increased. Our results also suggested that human exposure to OPs might be correlated with DNA oxidative stress for residents in e-waste dismantling areas. To our knowledge, this study is the first to report the urinary levels of mOPs in China and examine the association between OP exposure and 8-OHdG in humans.

  13. A mechanism-based 3D-QSAR approach for classification and prediction of acetylcholinesterase inhibitory potency of organophosphate and carbamate analogs

    NASA Astrophysics Data System (ADS)

    Lee, Sehan; Barron, Mace G.

    2016-04-01

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π-π interaction with Trp86 is necessary for strong inhibition of AChE. Our combined computation approach provided detailed understanding of the mechanism of action of OP and carbamate compounds and may be useful for screening a diversity of chemical structures for AChE inhibitory potency.

  14. Workshop on Alternatives to Animals in Research Held in Suffield, Ralston, Alberta on 16-17 September 1987

    DTIC Science & Technology

    1989-10-01

    UNCLASSIFIED UNCLASSIFIED 48 SUMMARY OF OP AND CARBAMATE INTERACTIONS IN THE ACUTE INHIBITION OF CHOLINESTERASE ACTIVITY IN RAT BRAIN NEURAL CELL AGGREGATE...for the past three years, we have been study- ing the toxicity of a number of organophosphates and carbamates on neural cell aggregate cultures. The...the temporary acute exposure to high concentrations of the chemical. In the occupational setting, accidental discharge may occur, resulting in acute

  15. Effects of the organophosphate insecticides phosmet and chlorpyrifos on trophoblast JEG-3 cell death, proliferation and inflammatory molecule production.

    PubMed

    Guiñazú, Natalia; Rena, Viviana; Genti-Raimondi, Susana; Rivero, Virginia; Magnarelli, Gladis

    2012-04-01

    Epidemiological data have associated environmental organophosphate insecticide (OP) exposure during pregnancy with fetal growth deficits. To better understand OP injury that may adversely affect pregnancy, we used the JEG-3 choriocarcinoma cell line, which provide a recognized in vitro model to study placental function. The effects of the OP phosmet (Pm) and chlorpyrifos (Cp) on JEG-3 cells viability, proliferation, cell cycle and inflammatory molecule production were evaluated. Both insecticides affected cellular viability in a concentration- and time-dependent manner, inducing apoptosis and decreasing [(3)H]-thymidine incorporation. However, only Pm reduced DNA synthesis independently of cellular death and decreased the cell percentage at the S-phase. Unlike apoptosis, TNFα production varied with the concentration tested, suggesting that other TNFα independent mechanisms might trigger cell death. No induction of the inflammatory molecule nitric oxide was detected. The mRNA levels of pro-inflammatory IL-6, IL-17 and the anti-inflammatory IL-13 cytokines were differentially modulated. These findings show that Pm and Cp generate a specific toxicity signature, altering cell viability and inducing an inflammatory cytokine profile, suggesting that trophoblasts may represent a possible target for OP adverse effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers

    PubMed Central

    Pang, Zhiqing; Hu, Che-Ming J.; Fang, Ronnie H.; Luk, Brian T.; Gao, Weiwei; Wang, Fei; Chuluun, Erdembileg; Angsantikul, Pavimol; Thamphiwatana, Soracha; Lu, Weiyue; Jiang, Xinguo; Zhang, Liangfang

    2016-01-01

    Organophosphate poisoning is highly lethal as organophosphates, which are commonly found in insecticides and nerve agents, cause irreversible phosphorylation and inactivation of acetylcholinesterase (AChE), leading to neuromuscular disorders via accumulation of acetylcholine in the body. Direct interception of organophosphates in the systemic circulation thus provides a desirable strategy in treatment of the condition. Inspired by the presence of acetylcholinesterase on red blood cell (RBC) membranes, we explored a biomimetic nanoparticle consisting of a polymeric core surrounded by RBC membranes to serve as an anti-organophosphate agent. Through in vitro studies, we demonstrated that the biomimetic nanoparticles retain the enzymatic activity of membrane-bound AChE and are able to bind to a model organophosphate, dichlorvos, precluding its inhibitory effect on other enzymatic substrates. In a mouse model of organophosphate poisoning, the nanoparticles were shown to improve the AChE activity in the blood and markedly improved the survival of dichlorvos-challenged mice. PMID:26053868

  17. Characterization and in vitro sensitivity of cholinesterases of gilthead seabream (Sparus aurata) to organophosphate pesticides.

    PubMed

    Albendín, G; Arellano, J M; Mánuel-Vez, M P; Sarasquete, C; Arufe, M I

    2017-04-01

    The characterization of cholinesterase activity in brain and muscle of gilthead seabream was carried out using four specific substrates and three selective inhibitors. In addition, K m and V max were calculated from the Michaelis-Menten equation for ASCh and BSCh substrates. Finally, the in vitro sensitivity of brain and muscle cholinesterases to three organophosphates (OPs) was also investigated by estimating inhibition kinetics. The results indicate that AChE is the enzyme present in the brain, whereas in muscle, a typical AChE form is present along with an atypical form of BChE. Very low ChE activity was found in plasma with all substrates used. The inhibitory potency of the studied OPs on brain and muscle AChEs based on bimolecular inhibition constants (k i ) was: omethoate < dichlorvos < azinphosmethyl-oxon. Furthermore, muscle BChE was found to be several orders of magnitude (from 2 to 4) more sensitive than brain and muscle AChE inhibition by dichlorvos and omethoate.

  18. [Effect of Huperzine A on neural lesion of acute organophosphate poisoning in mice].

    PubMed

    Liu, Li; Wang, Jian; Xie, Guangyun; Sun, Jinxiu

    2013-05-01

    Effects of neurophathologic changes and expression of Glu and 60 nNOS were observed in acute isocarbophos and phoxim poisoning in mice. KM male mice were randomly divided into three groups, which were control, non-treated and Huperzine A (HupA)-treated groups. The control group was given tween-80. Nontreated group was given isocarbophos (14.7 mg/kg) or phoxim (1702 mg/kg). HupA-treated group was given HupA 2h before phoxim or isocarbophos. Twenty-four hours after exposure, the whole brain was removed and adjacent coronal sections was obtained. One part of sections were stained with toluidine blue. The part of sections were used to assessed the expression of Glu and nNOS in the cortex and hippocampal of brain by immunohistochemistry. Compared to control group, non-treated group was observed nissal body nembers reduced and dyeing light. The animals of HupA protective group were observed nissal body nembers reduced, but the lesional degree was lighter obviously than non-treated group. The statistically reduced of the expression of Glu (P<0.01), the elevation of nNOS (P<0.01), after Isocarbophos intoxication were observed. Compared to non-treated group, the significant elevation of Glu (P<0.01) and reduced of nNOS (P<0.01) was observed on HupA-treated groups. Whereas for phoxim treatment, no changes were observed. HupA have protective effect against glutamatergic systems disorder caused by Isocarbophos poisoning. Administration of HupA have no effects of the neurotransmitter changes induces by acute poisoning of phoxim. It is different for the toxic effect mechanism of the two organophosphate.

  19. The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka

    PubMed Central

    Jayawardane, Pradeepa; Dawson, Andrew H; Weerasinghe, Vajira; Karalliedde, Lakshman; Buckley, Nicholas A; Senanayake, Nimal

    2008-01-01

    Background Intermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulation (RNS) predictors of IMS that would assist in patient management and clinical research. Methods and Findings Seventy-eight consenting symptomatic patients with organophosphate poisoning were assessed prospectively with daily physical examination and RNS. RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. The study was conducted as a prospective observational cohort study in the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients using a priori clinical diagnostic criteria, and five of them developed respiratory failure. All ten patients showed progressive RNS changes correlating with the severity of IMS. A decrement-increment was observed at intermediate and high frequencies preceding the onset of clinical signs of IMS. As the patient developed clinical signs of IMS, decrement-increment was progressively noted at low and intermediate frequencies and a combination of decrement-increment and repetitive fade or severe decrement was noted at high frequencies. Severe decrement preceded respiratory failure in four patients. Thirty patients developed forme fruste IMS with less severe weakness not progressing to respiratory failure whose RNS was characterized by decrement-increment or a combination of decrement-increment and repetitive fade but never severe decrements. Conclusions Characteristic changes in RNS, preceding the development of IMS, help to identify a subgroup of patients at high risk of developing respiratory failure. The forme fruste IMS with the characteristic early changes on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and precede the diagnosis and complications of IMS. Thus they may be useful in clinical management and research. PMID:18630983

  20. Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Read, David J.; Li Yong; Chao, Moses V.

    2010-05-15

    Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but maymore » incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.« less

  1. Poisoning severity score, APACHE II and GCS: effective clinical indices for estimating severity and predicting outcome of acute organophosphorus and carbamate poisoning.

    PubMed

    Sam, Kishore Gnana; Kondabolu, Krishnakanth; Pati, Dipanwita; Kamath, Asha; Pradeep Kumar, G; Rao, Padma G M

    2009-07-01

    Self-poisoning with organophosphorus (OP) compounds is a major cause of morbidity and mortality across South Asian countries. To develop uniform and effective management guidelines, the severity of acute OP poisoning should be assessed through scientific methods and a clinical database should be maintained. A prospective descriptive survey was carried out to assess the utility of severity scales in predicting the outcome of 71 organophosphate (OP) and carbamate poisoning patients admitted during a one year period at the Kasturba Hospital, Manipal, India. The Glasgow coma scale (GCS) scores, acute physiology and chronic health evaluation II (APACHE II) scores, predicted mortality rate (PMR) and Poisoning severity score (PSS) were estimated within 24h of admission. Significant correlation (P<0.05) between PSS and GCS and APACHE II and PMR scores were observed with the PSS scores predicting mortality significantly (P< or =0.001). A total of 84.5% patients improved after treatment while 8.5% of the patients were discharged with severe morbidity. The mortality rate was 7.0%. Suicidal poisoning was observed to be the major cause (80.2%), while other reasons attributed were occupational (9.1%), accidental (6.6%), homicidal (1.6%) and unknown (2.5%) reasons. This study highlights the application of clinical indices like GCS, APACHE, PMR and severity scores in predicting mortality and may be considered for planning standard treatment guidelines.

  2. An exploratory study; the therapeutic effects of premixed activated charcoal-sorbitol administration in patients poisoned with organophosphate pesticide.

    PubMed

    Moon, Jeongmi; Chun, Byeongjo; Song, Kyounghwan

    2015-02-01

    The effects of activated charcoal (AC) mixed with cathartics for gastric decontamination in the management of organophosphate (OP) poisoning remain unknown due to limited clinical evidence. This exploratory study assessed the effectiveness of premixed AC-sorbitol as a treatment for OP poisoning. This retrospective observational case study included patients who either did not receive AC-sorbitol or received a single dose of AC-sorbitol within 24 h after OP ingestion. The patients were divided into three groups: no AC-sorbitol treatment, patients who received AC-sorbitol within 1 h of OP ingestion, and patients who received AC-sorbitol more than 1 h after OP ingestion. Mortality, the development of respiratory failure, and the duration of mechanical ventilation were used as outcome measurements for effectiveness, whereas aspiration pneumonia and electrolyte imbalance were employed as safety measurements. Among 262 patients with OP poisoning, 198 were included. Of these, 133 patients did not receive AC-sorbitol, whereas 14 and 51 patients received AC-sorbitol within 1 h or more than 1 h after ingestion, respectively. The time from ingestion to hospital arrival and time from ingestion to administration of atropine and pralidoxime differed among the groups, whereas other characteristics, including age, amount ingested, and type of ingested OP, were similar among the groups. Univariate and multivariate analysis demonstrated that the administration of AC-sorbitol was not associated with outcome measures for effectiveness and did not significantly increase either aspiration pneumonia or electrolyte imbalances during hospitalization. The administration of AC-sorbitol exerted neither beneficial nor harmful effects on the outcomes of OP-poisoned patients regardless of the time from OP ingestion to administration, compared with those of patients who did not receive AC-sorbitol. However, this study enrolled a small number of patients who received AC-sorbitol; further qualified

  3. Increased risk of deep vein thrombosis and pulmonary thromboembolism in patients with organophosphate intoxication: a nationwide prospective cohort study.

    PubMed

    Lim, Yun-Ping; Lin, Cheng-Li; Hung, Dong-Zong; Ma, Wei-Chih; Lin, Yen-Ning; Kao, Chia-Hung

    2015-01-01

    Organophosphate (OP) poisoning is a critical cause of morbidity and mortality worldwide. We conducted a nationwide longitudinal cohort study to investigate the development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) among patients admitted with OP intoxication.We identified patients with OP intoxication by using the Taiwan National Health Insurance Research Database and enrolled 9223 patients who were hospitalized for OP intoxication between 2000 and 2011. OP intoxication was diagnosed based on a clinical assessment and serum acetylcholinesterase levels at the time of hospital admission. Each patient in the OP intoxication cohort was randomly frequency matched with 4 patients without OP intoxication based on their age, sex, and index year (36,892 patients as control cohort), and all patients were observed from the index date until the appearance of a DVT or a PTE event, or until December 31, 2011. We analyzed the risks of DVT and PTE by using Cox proportional hazards regression models that included the demographic variables of sex, age, and comorbidities (eg, hypertension, diabetes, cerebral vascular disease, heart failure, all cancer types, and lower leg fracture or surgery).The results revealed a significantly increased risk of developing DVT among patients with OP poisoning (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.03-2.34) but not PTE (adjusted HR = 1.44; 95% CI = 0.83-2.52). Among the patients without comorbidities, the OP poisoning patients compared with controls had a higher adjusted HR of 2.12 (95% CI = 1.21-3.71) for DVT.The results of this nationwide cohort study indicate that the risk of developing DVT is markedly higher in patients with OP intoxication compared with that of the general population.

  4. Biomonitoring of organophosphate exposure of pesticide sprayers and comparison of exposure levels with other population groups in Thessaly (Greece).

    PubMed

    Koureas, Michalis; Tsakalof, Andreas; Tzatzarakis, Manolis; Vakonaki, Elena; Tsatsakis, Aristidis; Hadjichristodoulou, Christos

    2014-02-01

    To evaluate the exposure of different population groups in Thessaly (Greece) to organophosphate pesticides (OPs) and investigate the dependence of exposure levels on pesticide application practices, personal protective and hygienic measures taken. For the exposure assessment, four dialkyl phosphate (DAP) metabolites of organophosphate pesticides were quantified in spot urine samples of 77 pesticide sprayers, 75 residents of the studied agricultural area non-involved in agricultural activities and 112 urban residents who served as a control group. Structured questionnaires were used to record demographic characteristics, pesticide application parameters and protective measures taken. Univariate and multivariate analysis of the obtained cross-sectional data was performed to identify potential risk factors associated with biomarker levels. It was found that total DAP median level in the sprayers' group was 24.9 μg/g creatinine (IQR: 13.0-42.1), while the rural and urban residents had significantly lower (p<0.001) levels of 11.3 μg/g creatinine (IQR: 5.3-18.7) and 11.9 μg/g creatinine (IQR: 6.3-20.3), respectively. In sprayers who had recently applied an OP pesticide (n=28), the median levels of DAP metabolites were 31.8 μg/g creatinine (IQR: 22.3-117.2). Logistic regression analysis showed that the use of full body coveralls while handling and spraying pesticides was significantly associated with lower DAP levels (OR 4.05, 95% CI 1.22 to 13.46). Also, changing clothes immediately after accidental contamination of clothing with pesticide amounts was found to be significantly associated with lower exposure levels (OR 4.04, CI 1.05 to 15.57). Our study findings confirm the increased exposure to OPs in pesticide sprayers and underline the importance of protective measures especially those that focus on dermal exposure mitigation.

  5. Organophosphate pesticide method development and presence of chlorpyrifos in the feet of nearctic-neotropical migratory songbirds from Canada that over-winter in Central America agricultural areas.

    PubMed

    Alharbi, Hattan A; Letcher, Robert J; Mineau, Pierre; Chen, Da; Chu, Shaogang

    2016-02-01

    Recent modeling analysis suggests that numerous birds may be at risk of acute poisoning in insecticide-treated fields. Although the majority of avian field studies on pesticides have focused on treated seed, granule, insect or vegetation (oral exposure) ingestion, dermal exposure is an important exposure route when birds come into contact with deposited pesticides on foliage and other surfaces. Some nearctic-neotropical migratory songbirds are likely exposed to pesticides on their non-breeding habitats and include treated crops, plantations or farmlands. In the present study, we developed a method for four environmentally-relevant organophosphate (OP) pesticides (fenthion, fenamiphos, chlorpyrifos and diazinon) in the feet of migratory songbirds (i.e. Common yellowthroat, Gray catbird, Indigo bunting, America redstart, Northern waterthrush, Northern parula, and an additional 12 species of warblers). A total of 190 specimens of the 18 species of songbirds were sampled from available window-killed birds (spring of 2007 and 2011) in downtown Toronto, Canada. The species that were available most likely over-wintered in Mexican/Central American crops such as citrus, coffee and cacao. The feet of the dead birds were sampled and where OP foot exposure likely occurred during over-wintering foraging on pesticide-treated crops. Chlorpyrifos was the only measurable OP (pg mg feet weight(-1)) and in the 2011-collected feet of Black throated blue warbler (0.5), Tennessee warbler (1.0), Northern parula (1.2), Northern waterthrush (0.6), Common yellowthroat (1.0) and the Blue winged warbler (0.9). Dermal contact with OP pesticides during over-wintering in agricultural areas resulted in low levels of chlorpyrifos and long time retention on the feet of a subset of songbirds. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  6. A Model of Medical Countermeasures for Organophosphates

    DTIC Science & Technology

    2015-10-01

    Animal Data ................................................................. 51 6.2.1. Verifying AChE Activity ...17 Figure 4-3. Model Output for AChE Activity and Free/Stimulated Receptor Fraction with No OP Exposure...Figure 6-1. Sarin Model Output Compared to Individual AChE Activity in Acute Phase Following Tokyo Sarin Attack

  7. Mechanism behind Resistance against the Organophosphate Azamethiphos in Salmon Lice (Lepeophtheirus salmonis)

    PubMed Central

    Kaur, Kiranpreet; Helgesen, Kari Olli; Bakke, Marit Jørgensen; Horsberg, Tor Einar

    2015-01-01

    Acetylcholinesterase (AChE) is the primary target for organophosphates (OP). Several mutations have been reported in AChE to be associated with the reduced sensitivity against OP in various arthropods. However, to the best of our knowledge, no such reports are available for Lepeophtheirus salmonis. Hence, in the present study, we aimed to determine the association of AChE(s) gene(s) with resistance against OP. We screened the AChE genes (L. salmonis ace1a and ace1b) in two salmon lice populations: one sensitive (n=5) and the other resistant (n=5) for azamethiphos, a commonly used OP in salmon farming. The screening led to the identification of a missense mutation Phe362Tyr in L. salmonis ace1a, (corresponding to Phe331 in Torpedo californica AChE) in all the samples of the resistant population. We confirmed the potential role of the mutation, with reduced sensitivity against azamethiphos in L. salmonis, by screening for Phe362Tyr in 2 sensitive and 5 resistant strains. The significantly higher frequency of the mutant allele (362Tyr) in the resistant strains clearly indicated the possible association of Phe362Tyr mutation in L. salmonis ace1a with resistance towards azamethiphos. The 3D modelling, short term survival experiments and enzymatic assays further supported the imperative role of Phe362Tyr in reduced sensitivity of L. salmonis for azamethiphos. Based on all these observations, the present study, for the first time, presents the mechanism of resistance in L. salmonis against azamethiphos. In addition, we developed a rapid diagnostic tool for the high throughput screening of Phe362Tyr mutation using High Resolution Melt analysis. PMID:25893248

  8. An enantiomer-based virtual screening approach: Discovery of chiral organophosphates as acetyl cholinesterase inhibitors.

    PubMed

    Zhang, Aiqian; Mu, Yunsong; Wu, Fengchang

    2017-04-01

    Chiral organophosphates (OPs) have been used widely around the world, very little is known about binding mechanisms with biological macromolecules. An in-depth understanding of the stereo selectivity of human AChE and discovering bioactive enantiomers of OPs can decrease health risks of these chiral chemicals. In the present study, a flexible molecular docking approach was conducted to investigate different binding modes of twelve phosphorus enantiomers. A pharmacophore model was then developed on basis of the bioactive conformations of these compounds. After virtual screening, twenty-four potential bioactive compounds were found, of which three compounds (Ethyl p-nitrophenyl phenylphosphonate (EPN), 1-naphthaleneacetic anhydride and N,4-dimethyl-N-phenyl-benzenesulfonamide) were tested by use of different in vitro assays. S-isomer of EPN was also found to exhibit greater inhibitory activity towards human AChE than the corresponding R-isomer. These findings affirm that stereochemistry plays a crucial role in virtual screening, and provide a new insight into designing safer organ phosphorus pesticides on human health. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Nanoparticle-Based Electrochemical Immunosensor for the Detection of Phosphorylated Acetylcholinesterase: An Exposure Biomarker of Organophosphate Pesticides and Nerve AgentsOrganophosphate Pesticides and Nerve Agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Guodong; Wang, Jun; Barry, Richard C.

    A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE) adducts, which is a potential exposure biomarker for organophosphate pesticides (OP) and chemical warfare nerve agent exposures. Zirconia nanoparticles (ZrO2 NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to track the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO2 NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemicalmore » stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as a model OP insecticide to prepare the phosphorylated AChE adduct to demonstrate the proof of principle for this sensor technology. The paraoxon-AChE adduct was characterized by Fourier Transform Infrared Spectrum, and the binding affinity of anti-AChE to the paraoxon-AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO2 NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10 pM to 4 nM paraoxon-AChE, and the limit of detection is estimated to be 8 pM. This new nanoparticle-based electrochemical immunosensor thus provides a sensitive and quantitative tool for biomonitoring exposure to OP pesticides and nerve agents.« less

  10. Enzymatic degradation of monocrotophos by extracellular fungal OP hydrolases.

    PubMed

    Jain, Rachna; Garg, Veena

    2013-11-01

    The present study explores the potential of extracellular fungal organophosphate (OP) hydrolase for the degradation of monocrotophos. Extracellular OP hydrolases were isolated and purified from five different fungal isolates viz. Aspergillus niger (M1), Aspergillus flavus (M2), Penicillium aculeatum (M3), Fusarium pallidoroseum (M4), and Macrophomina sp. (M5) by AmSO4 precipitation, dialysis, and G-100 chromatography. M3 showed highest percentage yield of 68.81 followed by 55.41 % for M1. Each of the purified enzyme fraction constituted of two different subunits of 33- and 67-kDa molecular weight. Optimum enzyme fraction (150 μg ml(-1)) rapidly degraded monocrotophos within 120 h in phosphorus-free liquid culture medium (CZM) with K deg of 0.0368, 0.0138, 0.048, 0.016, 0.0138, and 0.048 day(-1) and half-life of 0.79, 2.11, 0.6, 1.8, and 2.11 days for M1, M2, M3, M4, and M5, respectively. The results were further confirmed by high performance thin layer chromatography and Fourier transform infrared which indicate the disappearance of monocrotophos by hydrolytic cleavage of vinyl phosphate bond. The overall order of enzymatic degradation was found to be P. aculeatum > A. niger > F. pallidoroseum > A. flavus = Macrophomina sp. Hence, the study concludes that extracellular OP hydrolases efficiently degraded monocrotophos and could be used as a potential candidate for the detoxification of this neurotoxin pesticide.

  11. Quaternary and tertiary aldoxime antidotes for organophosphate exposure in a zebrafish model system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schmidt, Hayden R.; Radić, Zoran; Taylor, Palmer

    The zebrafish is rapidly becoming an important model system for screening of new therapeutics. Here we evaluated the zebrafish as a potential pharmacological model for screening novel oxime antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE). The k{sub i} values determined for chlorpyrifos oxon (CPO) and dichlorvos (DDVP) showed that CPO was a more potent inhibitor of both human and zebrafish AChE, but overall zebrafish AChE was less sensitive to OP inhibition. In contrast, aldoxime antidotes, the quaternary ammonium 2-PAM and tertiary amine RS-194B, showed generally similar overall reactivation kinetics, k{sub r}, in both zebrafish and human AChE. However, differences between themore » K{sub ox} and k{sub 2} constants suggest that zebrafish AChE associates more tightly with oximes, but has a slower maximal reactivation rate than human AChE. Homology modeling suggests that these kinetic differences result from divergences in the amino acids lining the entrance to the active site gorge. Although 2-PAM had the more favorable in vitro reactivation kinetics, RS-194B was more effective antidote in vivo. In intact zebrafish embryos, antidotal treatment with RS-194B rescued embryos from OP toxicity, whereas 2-PAM had no effect. Dechorionation of the embryos prior to antidotal treatment allowed both 2-PAM and RS-194B to rescue zebrafish embryos from OP toxicity. Interestingly, RS-194B and 2-PAM alone increased cholinergic motor activity in dechorionated embryos possibly due to the reversible inhibition kinetics, K{sub i} and αK{sub i}, of the oximes. Together these results demonstrate that the zebrafish at various developmental stages provides an excellent model for investigating membrane penetrant antidotes to OP exposure. - Highlights: • Zebrafish AChE shares significant structural similarities with human AChE. • OP-inhibited zebrafish and human AChE exhibit similar reactivation kinetics. • The zebrafish chorion is permeable to BBB penetrant

  12. Predictors of exposure to organophosphate pesticides in schoolchildren in the Province of Talca, Chile.

    PubMed

    Muñoz-Quezada, María Teresa; Iglesias, Verónica; Lucero, Boris; Steenland, Kyle; Barr, Dana Boyd; Levy, Karen; Ryan, P Barry; Alvarado, Sergio; Concha, Carlos

    2012-10-15

    Few data exist in Latin America concerning the association between organophosphate (OP) urinary metabolites and the consumption of fruits and vegetables and other exposure risk variables in schoolchildren. We collected samples of urine from 190 Chilean children aged 6-12 years, fruits and vegetables, water and soil from schools and homes, and sociodemographic data through a questionnaire. We measured urinary dialkylphosphate (DAP) OP metabolites and OP pesticide residues in food consumed by these 190 children during two seasons: December 2010 (summer) and May 2011 (fall). We analyzed the relationship between urinary DAP concentrations and pesticide residues in food, home pesticide use, and residential location. Diethylalkylphosphates (DEAP) and dimethylalkylphosphates (DMAP) were detected in urine in 76% and 27% of the samples, respectively. Factors associated with urinary DEAP included chlorpyrifos in consumed fruits (p<0.0001), urinary creatinine (p<0.0001), rural residence (p=0.02) and age less than 9 years (p=0.004). Factors associated with urinary DMAP included the presence of phosmet residues in fruits (p<0.0001), close proximity to a farm (p=0.002), home fenitrothion use (p=0.009), and season (p<0.0001). Urinary DAP levels in Chilean school children were high compared to previously reported studies. The presence of chlorpyrifos and phosmet residues in fruits was the major factor predicting urinary DAP metabolite concentrations in children. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Determination of organophosphate diesters in urine samples by a high-sensitivity method based on ultra high pressure liquid chromatography-triple quadrupole-mass spectrometry.

    PubMed

    Su, Guanyong; Letcher, Robert J; Yu, Hongxia

    2015-12-24

    Organophosphate (OP) diesters in urine samples have potential use as biomarkers of organism exposure to environmentally relevant OP triester precursors and in particular OP triester flame retardants. This present study developed a quantitatively sensitive ultra high pressure liquid chromatography (UHPLC-MS) based method for urine and the determination of OP diesters (i.e. diphenyl phosphate (DPHP), bis(2-chloroethyl) phosphate (BCEP), bis(2-chloroisopropyl) phosphate (BDCIPP), di-n-butyl phosphate (DNBP), di(2-ethylhexyl) phosphate (DEHP), bis(1-chloro-2-propyl) phosphate (BCIPP), and bis(2-butoxyethyl) phosphate (BBOEP)). Fortified with the 7 OP diesters, 1mL of human urine sample was cleaned up using weak anion exchange solid phase extraction and eluted with high ionic strength ammonium acetate buffer. Subsequently, 4 non-chlorinated OP diesters were directly determined using UHPLC-electrospray(-)-triple quadrupole-MS (UHPLC-ESI(-)-QqQ-MS), and UHPLC-ESI(+)-QqQ-MS was used for determination of 3 chlorinated OP diesters after methylation using diazomethane. Recovery efficiencies of OP diesters ranged from 88 to 160% at three spiking levels (0.4, 2 and 10ng/mL urine). Matrix effects (MEs) and method limits of quantification (MLOQs) were 15-134% and 0.10-0.32ng/mL urine, respectively. Concentrations of OP diesters in n=12 urine samples (from 4 Canadian residents, 2014) varied as follows, nd-<0.28 (DNBP), nd-1.29 (DPHP), nd-<0.28 (DEHP), <0.16-12.33 (BCEP), nd-1.17 (BCDIPP) and nd-0.68ng/mL (BCIPP). Copyright © 2015. Published by Elsevier B.V.

  14. Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis.

    PubMed

    Velmurugan, Ganesan; Ramprasath, Tharmarajan; Swaminathan, Krishnan; Mithieux, Gilles; Rajendhran, Jeyaprakash; Dhivakar, Mani; Parthasarathy, Ayothi; Babu, D D Venkatesh; Thumburaj, Leishman John; Freddy, Allen J; Dinakaran, Vasudevan; Puhari, Shanavas Syed Mohamed; Rekha, Balakrishnan; Christy, Yacob Jenifer; Anusha, Sivakumar; Divya, Ganesan; Suganya, Kannan; Meganathan, Boominathan; Kalyanaraman, Narayanan; Vasudevan, Varadaraj; Kamaraj, Raju; Karthik, Maruthan; Jeyakumar, Balakrishnan; Abhishek, Albert; Paul, Eldho; Pushpanathan, Muthuirulan; Rajmohan, Rajamani Koushick; Velayutham, Kumaravel; Lyon, Alexander R; Ramasamy, Subbiah

    2017-01-24

    Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process. Here we demonstrate a high prevalence of diabetes among people directly exposed to organophosphates in rural India (n = 3080). Correlation and linear regression analysis reveal a strong association between plasma organophosphate residues and HbA1c but no association with acetylcholine esterase was noticed. Chronic treatment of mice with organophosphate for 180 days confirms the induction of glucose intolerance with no significant change in acetylcholine esterase. Further fecal transplantation and culture transplantation experiments confirm the involvement of gut microbiota in organophosphate-induced glucose intolerance. Intestinal metatranscriptomic and host metabolomic analyses reveal that gut microbial organophosphate degradation produces short chain fatty acids like acetic acid, which induces gluconeogenesis and thereby accounts for glucose intolerance. Plasma organophosphate residues are positively correlated with fecal esterase activity and acetate level of human diabetes. Collectively, our results implicate gluconeogenesis as the key mechanism behind organophosphate-induced hyperglycemia, mediated by the organophosphate-degrading potential of gut microbiota. This study reveals the gut microbiome-mediated diabetogenic nature of organophosphates and hence that the usage of these insecticides should be reconsidered.

  15. Exposure to organophosphate pesticides and male hormone profile in floriculturist of the state of Morelos, Mexico.

    PubMed

    Blanco-Muñoz, Julia; Morales, Magally Mayanin; Lacasaña, Marina; Aguilar-Garduño, Clemente; Bassol, Susana; Cebrián, Mariano E

    2010-07-01

    Studies on experimental animals have found that organophosphate (OP) pesticides may act as endocrine disruptors; however, their effects on the human hormonal profile have not yet been adequately characterized. We evaluate the association between exposure to OP pesticides, measured through dialkyl phosphate (DAP) metabolites urinary levels, and the male hormone profile. A cross-sectional study was performed in 104 floriculturists of Morelos, Mexico. A structured questionnaire was applied to get information on sociodemographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, and work history. DAP metabolites [dimethylphosphate (DMP), dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate] were determined using gas-liquid chromatography. Serum levels of FSH, LH, prolactin, testosterone, inhibin B and estradiol were determined using enzyme-linked immunosorbent assay. Multiple linear regression was used to study the association between DAP metabolite levels and male hormonal profile. Data were adjusted by p,p'-dichlorodiphenyldichloroethene serum levels and other potential confounders. There was a negative association between inhibin B and urinary levels of DMP, DEP, DETP and total DAP metabolites. DEP levels were negatively associated with serum FSH concentrations, but marginally and positively associated with those of testosterone. DETP was marginally associated with lower LH serum levels. There were no other significant associations among OP metabolites and serum hormone levels. Inhibin B and FSH vary according to levels of DAP metabolites in men occupationally exposed to OP pesticides. These results suggest that OP pesticides could act as endocrine disruptors in humans; however, most hormonal values fell within the wide normal range and associations were small. There is, therefore, a need for further investigation to elucidate their biological and clinical

  16. Exposure of Preschool-Age Greek Children (RHEA Cohort) to Bisphenol A, Parabens, Phthalates, and Organophosphates.

    PubMed

    Myridakis, Antonis; Chalkiadaki, Georgia; Fotou, Marianna; Kogevinas, Manolis; Chatzi, Leda; Stephanou, Euripides G

    2016-01-19

    Phthalate esters (PEs), bisphenol A (BPA), and parabens (PBs), which are used in numerous consumer products, are known for their endocrine disrupting properties. Organophosphate chemicals (OPs), which form the basis of the majority of pesticides, are known for their neurotoxic activity in humans. All of these chemicals are associated with health problems to which children are more susceptible. Once they enter the human body, PEs, BPA, PBs, and OPs are metabolized and/or conjugated and finally excreted via urine. Hence, human exposure to these substances is examined through a determination of the urinary concentrations of their metabolites. This study assessed the exposure of Greek preschool-age children to PEs, BPA, PBs, and OPs by investigating the urinary levels of seven PEs metabolites, six PBs, BPA, and six dialkyl phosphate metabolites in five-hundred samples collected from 4-year-old children, subjects of the "RHEA" mother-child cohort in Crete, Greece. Daily intake of endocrine disruptors, calculated for 4 year old children, was lower than the corresponding daily intake for 2.5 year old children, which were determined in an earlier study of the same cohort. In some cases the daily intake levels exceeded the U.S. Environmental Protection Agency Tolerable Daily Intake (TDI) values and the EFSA Reference Doses (RfD) (e.g., for di-2-ethyl-hexyl phthalate, 3.6% and 1% of the children exceeded RfD and TDi, respectively). Exposure was linked to three main sources: PEs-BPA to plastic, PBs-diethyl phthalate to personal hygiene products, and OPs to food.

  17. Efficacy of the bone injection gun in the treatment of organophosphate poisoning.

    PubMed

    Eisenkraft, Arik; Gilat, Eran; Chapman, Shira; Baranes, Shlomo; Egoz, Inbal; Levy, Aharon

    2007-04-01

    Immediate administration of antidotal treatment is crucial in severe organophosphate (OP) poisoning and the use of an open intravenous (i.v.) line might also be required. The state of casualties might prevent getting access to their veins. The bone injection gun (BIG) was established as a simple method for introducing an intraosseous (i.o.) line and could be applied while wearing a protective suit. The present study followed the pharmacokinetics of the anticonvulsive drug midazolam after i.o. administration in pigs compared with i.v. and the common intramuscular (i.m.) administration. A new method for monitoring midazolam concentrations in plasma was developed. Plasma concentrations following both i.v. and i.o. administrations peaked at 2 min post injection and only at 10 min following the i.m. route. In an antidotal treatment study against paraoxone poisoning, the anticonvulsive effect of midazolam appeared immediately following i.o. administration, while it took 5-10 min to exhibit a similar effect following i.m. administration. This study indicates that the use of i.o. administration after OP poisoning might provide the necessary fast response for rapid termination of convulsions. The BIG might offer a convenient method for treating casualties in the chemical arena by teams wearing full protective gear. Copyright (c) 2007 John Wiley & Sons, Ltd.

  18. Detoxification of organophosphate nerve agents by bacterial phosphotriesterase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ghanem, Eman; Raushel, Frank M.

    2005-09-01

    Organophosphates have been widely used as insecticides and chemical warfare agents. The health risks associated with these agents have necessitated the need for better detoxification and bioremediation tools. Bacterial enzymes capable of hydrolyzing the lethal organophosphate nerve agents are of special interest. Phosphotriesterase (PTE) isolated from the soil bacteria Pseudomonas diminuta displays a significant rate enhancement and substrate promiscuity for the hydrolysis of organophosphate triesters. Directed evolution and rational redesign of the active site of PTE have led to the identification of new variants with enhanced catalytic efficiency and stereoselectivity toward the hydrolysis of organophosphate neurotoxins. PTE has been utilizedmore » to protect against organophosphate poisoning in vivo. Biotechnological applications of PTE for detection and decontamination of insecticides and chemical warfare agents are developing into useful tools. In this review, the catalytic properties and potential applications of this remarkable enzyme are discussed.« less

  19. Design of a macroalgae amperometric biosensor; application to the rapid monitoring of organophosphate insecticides in an agroecosystem.

    PubMed

    Nunes, G S; Lins, J A P; Silva, F G S; Araujo, L C; Silva, F E P S; Mendonça, C D; Badea, M; Hayat, A; Marty, J-L

    2014-09-01

    The immobilization of enzymes onto transducer support is a mature technology and has been successfully implemented to improve biocatalytic processes for diverse applications. However, there exists still need to design more sophisticated and specialized strategies to enhance the functional properties of the biosensors. In this work, a biosensor platform based on innovative fabrication strategy was designed, and employed for the detection of organophosphate (OP) in natural waters. The biosensor was prepared by incorporating acetylcholinesterase enzyme (AChE) to the graphite paste modified with tetracyanoquinodimethane (TCNQ) mediator, along with the use of a macroalgae (Cladaphropsis membranous) as a functional immobilization support. The novel immobilization design resulted in a synergic effect, and led to enhanced stability and sensitivity of the biosensor. The designed biosensor was used to analyze methyl parathion OP insecticide in water samples collected from a demonstrably contaminated lake of São Luis Island, Maranhão, Northeast of Brazil. Water analysis revealed that the aquatic ecosystem was polluted by sub-ppm concentrations of the OP insecticide, and a good correlation was found between values obtained through biosensor and GC-MS techniques. Our results demonstrated that macroalgae-biosensor could be used as a low-cost and sensitive screening method to detect target analyte. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Potent 3-Hydroxy-2-Pyridine Aldoxime Reactivators of Organophosphate-Inhibited Cholinesterases with Predicted Blood-Brain Barrier Penetration.

    PubMed

    Zorbaz, Tamara; Braïki, Anissa; Maraković, Nikola; Renou, Julien; de la Mora, Eugenio; Maček Hrvat, Nikolina; Katalinić, Maja; Silman, Israel; Sussman, Joel L; Mercey, Guillaume; Gomez, Catherine; Mougeot, Romain; Pérez, Belén; Baati, Rachid; Nachon, Florian; Weik, Martin; Jean, Ludovic; Kovarik, Zrinka; Renard, Pierre-Yves

    2018-04-19

    A new series of 3-hydroxy-2-pyridine aldoxime compounds have been designed, synthesised and tested in vitro, in silico, and ex vivo as reactivators of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) inhibited by organophosphates (OPs), for example, VX, sarin, cyclosarin, tabun, and paraoxon. The reactivation rates of three oximes (16-18) were determined to be greater than that of 2-PAM and comparable to that of HI-6, two pyridinium aldoximes currently used by the armies of several countries. The interactions important for a productive orientation of the oxime group within the OP-inhibited enzyme have been clarified by molecular-modelling studies, and by the resolution of the crystal structure of the complex of oxime 17 with Torpedo californica AChE. Blood-brain barrier penetration was predicted for oximes 15-18 based on their physicochemical properties and an in vitro brain membrane permeation assay. Among the evaluated compounds, two morpholine-3-hydroxypyridine aldoxime conjugates proved to be promising reactivators of OP-inhibited cholinesterases. Moreover, efficient ex vivo reactivation of phosphylated native cholinesterases by selected oximes enabled significant hydrolysis of VX, sarin, paraoxon, and cyclosarin in whole human blood, which indicates that the oximes have scavenging potential. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Noninvasive Biomonitoring Approaches to Determine Dosimetry and Risk Following Acute Chemical Exposure: Analysis of Lead or Organophosphate Insecticide in Saliva

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

    2004-04-01

    There is a need to develop approaches for assessing risk associated with acute exposures to a broad-range of chemical agents and to rapidly determine the potential implications to human health. Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants including heavy metals and pesticides. To advance the application of non-invasive biomonitoring a microfluidic/ electrochemical device has also been developed for the analysis of lead (Pb), using square wave anodic stripping voltammetry. Themore » system demonstrates a linear response over a broad concentration range (1 2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb-acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for non-invasive biomonitoring can provide a sensitive, and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these non-invasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for accessing acute exposure and health risk.« less

  2. Comparison of current recommended regimens of atropinization in organophosphate poisoning.

    PubMed

    Connors, Nicholas J; Harnett, Zachary H; Hoffman, Robert S

    2014-06-01

    Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.'s work, texts of Internal and Emergency Medicine, and electronic resources were reviewed for atropine dosing recommendations. For comparison, recommendations were assessed using the same mean dose (23.4 mg) and the highest dose (75 mg) of atropine as used in the original paper. Recommendations were also compared with the dosing regimen from the World Health Organization (WHO). Thirteen of the original recommendations were updated and 15 additional references were added giving a convenience sample of 28. Sufficient information to calculate time to targeted dose was provided by 24 of these samples. Compared to 2004, current recommendations have greatly increased the speed of atropinization with 13/24 able to reach the mean and high atropine dose within 30 min compared to 1/36 in 2004. In 2004, there were 13 regimens where the maximum time to reach 75 mg was over 18 h, whereas now, there are 2. While only one recommendation called for doubling the dose for faster escalation in 2004, 15 of the 24 current works include dose doubling. In 2004, Eddleston et al. called for an evidence-based guideline for the treatment of OP poisoning that could be disseminated worldwide. Many current recommendations can adequately treat patients within 1 h. While the WHO recommendations remain slow to treat patients with OP poisoning, other authorities are close to a consensus on rapid atropinization.

  3. Method for the determination of organophosphate insecticides in water, sediment and biota.

    PubMed

    Tse, Hung; Comba, Michael; Alaee, Mehran

    2004-01-01

    A procedure for the determination of 13 organophosphate insecticides (OPs) in water, sediment and biota at low ppb levels is described. Samples were extracted with dichloromethane or acetone/hexane and cleaned up with micro-column silica gel chromatography. Measurements were made by dual capillary column gas chromatography using both nitrogen-phosphorus (NPD) and electron capture (ECD) detection. Recoveries from fortified water samples ranged from 76% to 102% for all sample types. Practical detection limits ranged between 0.003 and 0.029 microg/l in natural water samples, 0.0004-0.005 microg/g w.w. for sediments, and 0.001-0.005 microg/g w.w for biota using the NPD and ECD method. Losses in sediments were experienced when sulphur was removed. Precision and accuracy were not affected in sediment samples where sulphur was not removed.

  4. Probiotic Lactobacillus rhamnosus Reduces Organophosphate Pesticide Absorption and Toxicity to Drosophila melanogaster

    PubMed Central

    Trinder, Mark; McDowell, Tim W.; Daisley, Brendan A.; Ali, Sohrab N.; Leong, Hon S.; Sumarah, Mark W.

    2016-01-01

    ABSTRACT Organophosphate pesticides used in agriculture can pose health risks to humans and wildlife. We hypothesized that dietary supplementation with Lactobacillus, a genus of commensal bacteria, would reduce absorption and toxicity of consumed organophosphate pesticides (parathion and chlorpyrifos [CP]). Several Lactobacillus species were screened for toleration of 100 ppm of CP or parathion in MRS broth based on 24-h growth curves. Certain Lactobacillus strains were unable to reach stationary-phase culture maxima and displayed an abnormal culture morphology in response to pesticide. Further characterization of commonly used, pesticide-tolerant and pesticide-susceptible, probiotic Lactobacillus rhamnosus strain GG (LGG) and L. rhamnosus strain GR-1 (LGR-1), respectively, revealed that both strains could significantly sequester organophosphate pesticides from solution after 24-h coincubations. This effect was independent of metabolic activity, as L. rhamnosus GG did not hydrolyze CP and no difference in organophosphate sequestration was observed between live and heat-killed strains. Furthermore, LGR-1 and LGG reduced the absorption of 100 μM parathion or CP in a Caco-2 Transwell model of the small intestine epithelium. To determine the effect of sequestration on acute toxicity, newly eclosed Drosophila melanogaster flies were exposed to food containing 10 μM CP with or without supplementation with live LGG. Supplementation with LGG simultaneously, but not with administration of CP 3 days prior (prophylactically), mitigated CP-induced mortality. In summary, the results suggest that L. rhamnosus may be useful for reducing toxic organophosphate pesticide exposure via passive binding. These findings could be transferable to clinical and livestock applications due to affordability and practical ability to supplement products with food-grade bacteria. IMPORTANCE The consequences of environmental pesticide pollution due to widespread usage in agriculture and soil

  5. Probiotic Lactobacillus rhamnosus Reduces Organophosphate Pesticide Absorption and Toxicity to Drosophila melanogaster.

    PubMed

    Trinder, Mark; McDowell, Tim W; Daisley, Brendan A; Ali, Sohrab N; Leong, Hon S; Sumarah, Mark W; Reid, Gregor

    2016-10-15

    Organophosphate pesticides used in agriculture can pose health risks to humans and wildlife. We hypothesized that dietary supplementation with Lactobacillus, a genus of commensal bacteria, would reduce absorption and toxicity of consumed organophosphate pesticides (parathion and chlorpyrifos [CP]). Several Lactobacillus species were screened for toleration of 100 ppm of CP or parathion in MRS broth based on 24-h growth curves. Certain Lactobacillus strains were unable to reach stationary-phase culture maxima and displayed an abnormal culture morphology in response to pesticide. Further characterization of commonly used, pesticide-tolerant and pesticide-susceptible, probiotic Lactobacillus rhamnosus strain GG (LGG) and L. rhamnosus strain GR-1 (LGR-1), respectively, revealed that both strains could significantly sequester organophosphate pesticides from solution after 24-h coincubations. This effect was independent of metabolic activity, as L. rhamnosus GG did not hydrolyze CP and no difference in organophosphate sequestration was observed between live and heat-killed strains. Furthermore, LGR-1 and LGG reduced the absorption of 100 μM parathion or CP in a Caco-2 Transwell model of the small intestine epithelium. To determine the effect of sequestration on acute toxicity, newly eclosed Drosophila melanogaster flies were exposed to food containing 10 μM CP with or without supplementation with live LGG. Supplementation with LGG simultaneously, but not with administration of CP 3 days prior (prophylactically), mitigated CP-induced mortality. In summary, the results suggest that L. rhamnosus may be useful for reducing toxic organophosphate pesticide exposure via passive binding. These findings could be transferable to clinical and livestock applications due to affordability and practical ability to supplement products with food-grade bacteria. The consequences of environmental pesticide pollution due to widespread usage in agriculture and soil leaching are becoming a

  6. Measurement of cholinesterase enzyme activity before and after exposure to organophosphate pesticides in farmers of a suburb region of Mazandaran, a northern province of Iran.

    PubMed

    Pakravan, N; Shokrzadeh, M; Bari, M A Khalat; Shadboorestan, Amir

    2016-03-01

    Accidental toxicity by organophosphate (OP) agents may occur among farmers during spraying season due to improper use and handling. Plasma cholinesterase (ChE) activity measurement is recommended to monitor the extent of exposure to the OP agent. The aim of the current study was to measure plasma ChE activity before and after exposure with OP pesticides. This was a prospective study conducted on 36 farmers working in the farm field. The plasma ChE level was measured before spraying and 2 days and 8 weeks after spraying season and exposure to OP agent. Farmers were observed for clinical signs and symptoms of toxicity after exposure. Vertimac was the most common agent used by farmers followed by diazinon and chlorpyrifos. The plasma ChE level significantly decreased after exposure by over 50%. The level returned to preexposure level after 8 weeks. Exposure to OP pesticide is a major concern in the developing countries. More than 50% reduction in the plasma ChE activity after spraying is an alarming message for health-care system and policy makers. Furthermore, workplace evaluation, serial ChE monitoring, and appropriate training and education to exposed individuals would be initial important steps to avoid the toxicity or reduce the severity of poisoning. © The Author(s) 2015.

  7. Acute toxicity of some nerve agents and pesticides in rats.

    PubMed

    Misik, Jan; Pavlikova, Ruzena; Cabal, Jiri; Kuca, Kamil

    2015-01-01

    Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg(-1)) 2, 4, and 24 hours post exposure. V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg(-1) (VX, i.m.) to 1.402 mg kg(-1) (Russian VX, p.o.), followed by G-agents (LD50 = 0.069 mg kg(-1)/soman, i.m./ - 117.9 mg kg(-1)/sarin, p.c./), organophosphate POX and DFP (LD50 = 0.321 mg kg(-1)/POX, i.m./ - 420 mg kg(-1)/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD50 = 0.0082 mg kg(-1)/VX/ - 1.399 mg kg(-1)/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD50 = 0.085 mg kg(-1)/VX/ - 420 mg kg(-1)/DFP/). The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.

  8. Reliability of concentrations of organophosphate pesticide metabolites in serial urine specimens from pregnancy in the Generation R Study.

    PubMed

    Spaan, Suzanne; Pronk, Anjoeka; Koch, Holger M; Jusko, Todd A; Jaddoe, Vincent W V; Shaw, Pamela A; Tiemeier, Henning M; Hofman, Albert; Pierik, Frank H; Longnecker, Matthew P

    2015-05-01

    The widespread use of organophosphate (OP) pesticides has resulted in ubiquitous exposure in humans, primarily through their diet. Exposure to OP pesticides may have adverse health effects, including neurobehavioral deficits in children. The optimal design of new studies requires data on the reliability of urinary measures of exposure. In the present study, urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined in 120 pregnant women participating in the Generation R Study in Rotterdam. Intra-class correlation coefficients (ICCs) across serial urine specimens taken at <18, 18-25, and >25 weeks of pregnancy were determined to assess reliability. Geometric mean total DAP metabolite concentrations were 229 (GSD 2.2), 240 (GSD 2.1), and 224 (GSD 2.2) nmol/g creatinine across the three periods of gestation. Metabolite concentrations from the serial urine specimens in general correlated moderately. The ICCs for the six DAP metabolites ranged from 0.14 to 0.38 (0.30 for total DAPs), indicating weak to moderate reliability. Although the DAP metabolite levels observed in this study are slightly higher and slightly more correlated than in previous studies, the low to moderate reliability indicates a high degree of within-person variability, which presents challenges for designing well-powered epidemiological studies.

  9. Reliability of concentrations of organophosphate pesticide metabolites in serial urine specimens from pregnancy in the Generation R study

    PubMed Central

    Spaan, Suzanne; Pronk, Anjoeka; Koch, Holger M.; Jusko, Todd A.; Jaddoe, Vincent W.V.; Shaw, Pamela A.; Tiemeier, Henning M.; Hofman, Albert; Pierik, Frank H.; Longnecker, Matthew P.

    2014-01-01

    The widespread use of organophosphate (OP) pesticides has resulted in ubiquitous exposure in humans, primarily through their diet. Exposure to OP pesticides may have adverse health effects, including neurobehavioral deficits in children. The optimal design of new studies requires data on the reliability of urinary measures of exposure. In the present study, urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined in 120 pregnant women participating in the Generation R Study in Rotterdam. Intra-class correlation coefficients (ICCs) across serial urine specimens taken at <18, 18–25, and >25 weeks of pregnancy were determined to assess reliability. Geometric mean total DAP metabolite concentrations were 229 (GSD 2.2), 240 (GSD 2.1), and 224 (GSD 2.2) nmol/g creatinine across the three periods of gestation. Metabolite concentrations from the serial urine specimens in general correlated moderately. The ICCs for the six DAP metabolites ranged from 0.14 to 0.38 (0.30 for total DAPs), indicating weak to moderate reliability. Although the DAP metabolite levels observed in this study are slightly higher and slightly more correlated than in previous studies, the low to moderate reliability indicates a high degree of within-person variability, which presents challenges for designing well-powered epidemiologic studies. PMID:25515376

  10. Organophosphorus Compounds at 80: Some Old and New Issues.

    PubMed

    Costa, Lucio G

    2018-03-01

    One of the major classes of pesticides is that of the organophosphates (OPs). Initial developments date back almost 2 centuries but it was only in the mid-1940s that OPs reached a prominent status as insecticides, a status that, albeit declining, is still ongoing. OPs are highly toxic to nontarget species including humans, the primary effects being an acute cholinergic toxicity (responsible for thousands of poisoning each year) and a delayed polyneuropathy. Several issues of current debate and investigation on the toxicology of OPs are discussed in this brief review. These include (1) possible additional targets of OPs, (2) OPs as developmental neurotoxicants, (3) OPs and neurodegenerative diseases, (4) OPs and the "aerotoxic syndrome," (5) OPs and the microbiome, and (6) OPs and cancer. Some of these issues have been debated and studied for some time, while others are newer, suggesting that the study of the toxicology of OPs will remain an important scientific and public health issue for years to come.

  11. Occupational determinants of serum cholinesterase inhibition among organophosphate-exposed agricultural pesticide handlers in Washington State

    PubMed Central

    Hofmann, Jonathan N; Keifer, Matthew C; De Roos, Anneclaire J; Fenske, Richard A; Furlong, Clement E; van Belle, Gerald; Checkoway, Harvey

    2010-01-01

    Objective To identify potential risk factors for serum cholinesterase (BuChE) inhibition among agricultural pesticide handlers exposed to organophosphate (OP) and N-methyl-carbamate (CB) insecticides. Methods We conducted a longitudinal study among 154 agricultural pesticide handlers who participated in the Washington State cholinesterase monitoring program in 2006 and 2007. BuChE inhibition was analyzed in relation to reported exposures before and after adjustment for potential confounders using linear regression. Odds ratios estimating the risk of ‘BuChE depression’ (>20% from baseline) were also calculated for selected exposures based on unconditional logistic regression analyses. Results An overall decrease in mean BuChE activity was observed among study participants at the time of follow-up testing during the OP/CB spray season relative to pre-season baseline levels (mean decrease of 5.6%, P < 0.001). Score for estimated cumulative exposure to OP/CB insecticides in the past 30 days was a significant predictor of BuChE inhibition (β = −1.74, P < 0.001). Several specific work practices and workplace conditions were associated with greater BuChE inhibition, including mixing/loading pesticides and cleaning spray equipment. Factors that were protective against BuChE inhibition included full-face respirator use, wearing chemical-resistant boots, and storing personal protective equipment in a locker at work. Conclusions Despite existing regulations, agricultural pesticide handlers continue to be exposed to OP/CB insecticides at levels resulting in BuChE inhibition. These findings suggest that modifying certain work practices could potentially reduce BuChE inhibition. Replication from other studies will be valuable. PMID:19819864

  12. Whole genome analysis of six organophosphate-degrading rhizobacteria reveals putative agrochemical degradation enzymes with broad substrate specificity.

    PubMed

    Iyer, Rupa; Iken, Brian; Damania, Ashish; Krieger, Jerry

    2018-05-01

    Six organophosphate-degrading bacterial strains collected from farm and ranch soil rhizospheres across the Houston-metropolitan area were identified as strains of Pseudomonas putida (CBF10-2), Pseudomonas stutzeri (ODKF13), Ochrobactrum anthropi (FRAF13), Stenotrophomonas maltophilia (CBF10-1), Achromobacter xylosoxidans (ADAF13), and Rhizobium radiobacter (GHKF11). Whole genome sequencing data was assessed for relevant genes, proteins, and pathways involved in the breakdown of agrochemicals. For comparative purposes, this analysis was expanded to also include data from deposited strains in the National Center for Biotechnology Information's (NCBI) database. This study revealed Zn-dependent metallo-β-lactamase (MBL)-fold proteins similar to OPHC2 first identified in P. pseudoalcaligenes as the likely agents of organophosphate (OP) hydrolysis in A. xylosoxidans ADAF13, S. maltophilia CBF10-1, O. anthropi FRAF13, and R. radiobacter GHKF11. A search of similar proteins within NCBI identified over 200 hits for bacterial genera and species with a similar OPHC2 domain. Taken together, we conclude from this data that intrinsic low-level OP hydrolytic activity is likely prevalent across the rhizosphere stemming from widespread OPHC2-like metalloenzymes. In addition, P. stutzeri ODKF13, P. putida CBF10-2, O. anthropi FRAF13, and R. radiobacter GHKF11 were found to harbor glycine oxidase (GO) enzymes that putatively possess low-level activity against the herbicide glyphosate. These bacterial GOs are reported to catalyze the degradation of glyphosate to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and suggest a possible link to AMPA that can be found in glyphosate-contaminated agricultural soil. The presence of aromatic degradation proteins were also detected in five of six study strains, but are attributed primarily to components of the widely distributed β-ketoadipate pathway found in many soil bacteria.

  13. Comparative study on short- and long-term behavioral consequences of organophosphate exposure: relationship to AChE mRNA expression.

    PubMed

    López-Granero, Caridad; Cardona, Diana; Giménez, Estela; Lozano, Rafael; Barril, José; Aschner, Michael; Sánchez-Santed, Fernando; Cañadas, Fernando

    2014-01-01

    Organophosphates (OPs) affect behavior by inhibiting acetylcholinesterase (AChE). While the cognitive short-term effects may be directly attributed to this inhibition, the mechanisms that underlie OP's long-term cognitive effects remain controversial and poorly understood. Accordingly, two experiments were designed to assess the effects of OPs on cognition, and to ascertain whether both the short- and long-term effects of are AChE-dependent. A single subcutaneous dose of 250 mg/kg chlorpyrifos (CPF), 1.5mg/kg diisopropylphosphorofluoridate (DFP) or 15 mg/kg parathion (PTN) was administered to male Wistar rats. Spatial learning was evaluated 72 h or 23 weeks after exposure, and impulsive choice was tested at 10 and 30 weeks following OPs administration (experiment 1 and 2, respectively). Brain soluble and membrane-bound AChE activity, synaptic AChE-S mRNA, read-through AChE-R mRNA and brain acylpeptide hydrolase (APH) activity (as alternative non-cholinergic target) were analyzed upon completion of the behavioral testing (17 and 37 weeks after OPs exposure). Both short- and long-term CPF treatment caused statistically significant effects on spatial learning, while PTN treatment led only to statistically significant short-term effects. Neither CPF, DFP nor PTN affected the long-term impulsivity response. Long-term exposure to CPF and DFP significantly decreased AChE-S and AChE-R mRNA, while in the PTN treated group only AChE-S mRNA levels were decreased. However, after long-term OP exposure, soluble and membrane-bound AChE activity was indistinguishable from controls. Finally, no changes were noted in brain APH activity in response to OP treatment. Taken together, this study demonstrates long-term effects of OPs on AChE-S and AChE-R mRNA in the absence of changes in AChE soluble and membrane-bound activity. Thus, changes in AChE mRNA expression imply non-catalytic properties of the AChE enzyme. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Functional paraoxonase 1 variants modify the risk of Parkinson's disease due to organophosphate exposure.

    PubMed

    Lee, Pei-Chen; Rhodes, Shannon L; Sinsheimer, Janet S; Bronstein, Jeff; Ritz, Beate

    2013-06-01

    We previously demonstrated that carriers of the "slower metabolizer" MM genotype of paraoxonase (PON1) who were also exposed to ambient organophosphate (OP) pesticides at their residences were at increased risk of developing Parkinson's disease (PD). Here, with a larger sample size, we extend our previous investigation to consider additional sources of ambient exposure and examined two additional functional PON1 variants. From 2001 to 2011, we enrolled incident cases of idiopathic PD and population controls living in central California. We genotyped three well-known functional PON1 SNPs: two exonic polymorphisms (PON1L55M and PON1Q192R) and the promoter region variant (PON1C-108T). Ambient exposures to diazinon, chlorpyrifos, and parathion at residential and workplace addresses were assessed using a validated geographic information system-based model incorporating records of agricultural pesticide applications in California. The odds ratio (OR) for Caucasians exposed to OPs at either residential or workplace addresses varied by PON1 genotype; for exposed carriers of the "faster" metabolizer genotypes, ML or LL, we estimated lower odds ratios (range, 1.20-1.39) than for exposed carriers of the "slower" metabolizer genotype MM (range, 1.78-2.45) relative to unexposed carriers of the faster genotypes. We observed similarly increased ORs for exposure across PON1Q192R genotypes, but no differences across PON1C-108T genotypes. The largest ORs were estimated for exposed carriers of both PON1192QQ and PON155MM (OR range, 2.84-3.57). Several functional PON1 variants may act together to modify PD risk for ambient OP exposures. While either PON1L55M or PON1Q192R may be sufficient to identify increased susceptibility, carriers of both slow metabolizer variants seem most susceptible to OP exposures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. The evaluation of acute physiology and chronic health evaluation II score, poisoning severity score, sequential organ failure assessment score combine with lactate to assess the prognosis of the patients with acute organophosphate pesticide poisoning.

    PubMed

    Yuan, Shaoxin; Gao, Yusong; Ji, Wenqing; Song, Junshuai; Mei, Xue

    2018-05-01

    The aim of this study was to assess the ability of acute physiology and chronic health evaluation II (APACHE II) score, poisoning severity score (PSS) as well as sequential organ failure assessment (SOFA) score combining with lactate (Lac) to predict mortality in the Emergency Department (ED) patients who were poisoned with organophosphate.A retrospective review of 59 stands-compliant patients was carried out. Receiver operating characteristic (ROC) curves were constructed based on the APACHE II score, PSS, SOFA score with or without Lac, respectively, and the areas under the ROC curve (AUCs) were determined to assess predictive value. According to SOFA-Lac (a combination of SOFA and Lac) classification standard, acute organophosphate pesticide poisoning (AOPP) patients were divided into low-risk and high-risk groups. Then mortality rates were compared between risk levels.Between survivors and non-survivors, there were significant differences in the APACHE II score, PSS, SOFA score, and Lac (all P < .05). The AUCs of the APACHE II score, PSS, and SOFA score were 0.876, 0.811, and 0.837, respectively. However, after combining with Lac, the AUCs were 0.922, 0.878, and 0.956, respectively. According to SOFA-Lac, the mortality of high-risk group was significantly higher than low-risk group (P < .05) and the patients of the non-survival group were all at high risk.These data suggest the APACHE II score, PSS, SOFA score can all predict the prognosis of AOPP patients. For its simplicity and objectivity, the SOFA score is a superior predictor. Lac significantly improved the predictive abilities of the 3 scoring systems, especially for the SOFA score. The SOFA-Lac system effectively distinguished the high-risk group from the low-risk group. Therefore, the SOFA-Lac system is significantly better at predicting mortality in AOPP patients.

  16. Organophosphate acetylcholine esterase inhibitor poisoning from a home-made shampoo

    PubMed Central

    Sadaka, Yair; Broides, Arnon; Tzion, Raffi Lev; Lifshitz, Matitiahu

    2011-01-01

    Organophosphate acetylcholine esterase inhibitor poisoning is a major health problem in children. We report an unusual cause of organophosphate acetylcholine esterase inhibitor poisoning. Two children were admitted to the pediatric intensive care unit due to organophosphate acetylcholine esterase inhibitor poisoning after exposure from a home-made shampoo that was used for the treatment of head lice. Owing to no obvious source of poisoning, the diagnosis of organophosphate acetylcholine esterase inhibitor poisoning in one of these patients was delayed. Both patients had an uneventful recovery. Organophosphate acetylcholine esterase inhibitor poisoning from home-made shampoo is possible. In cases where the mode of poisoning is unclear, direct questioning about the use of home-made shampoo is warranted, in these cases the skin and particularly the scalp should be rinsed thoroughly as soon as possible. PMID:21887044

  17. Organophosphate acetylcholine esterase inhibitor poisoning from a home-made shampoo.

    PubMed

    Sadaka, Yair; Broides, Arnon; Tzion, Raffi Lev; Lifshitz, Matitiahu

    2011-07-01

    Organophosphate acetylcholine esterase inhibitor poisoning is a major health problem in children. We report an unusual cause of organophosphate acetylcholine esterase inhibitor poisoning. Two children were admitted to the pediatric intensive care unit due to organophosphate acetylcholine esterase inhibitor poisoning after exposure from a home-made shampoo that was used for the treatment of head lice. Owing to no obvious source of poisoning, the diagnosis of organophosphate acetylcholine esterase inhibitor poisoning in one of these patients was delayed. Both patients had an uneventful recovery. Organophosphate acetylcholine esterase inhibitor poisoning from home-made shampoo is possible. In cases where the mode of poisoning is unclear, direct questioning about the use of home-made shampoo is warranted, in these cases the skin and particularly the scalp should be rinsed thoroughly as soon as possible.

  18. Acetylcholinesterases of Blood-feeding Flies and Ticks

    USDA-ARS?s Scientific Manuscript database

    Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer’s disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, ...

  19. Optimization of Therapeutic Strategies for Organophosphate Poisoning

    DTIC Science & Technology

    2008-03-01

    chemical (Szinicz, 2005:173). Researchers later created various forms of the organophosphate and applied the chemicals as insecticides (Szinicz, 2005:173...of organophosphorus insecticides and nerve agents (Cannard, 2006:87). Organophosphates poison an estimated 100,000 people each year throughout the...quantifiable result in order to facilitate comparison among different therapeutic strategies. Justification and Applicability Organophosphorus insecticides are

  20. ANDROGEN RECEPTOR ANTAGONISM BY THE ORGANOPHOSPHATE INSECTICIDE FENITROTHION

    EPA Science Inventory

    Androgen receptor antagonism by the organophosphate insecticide fenitrothion. Tamura, H., Maness, S.C., Reischmann, K. Dorman, D.C., Gray, L.E., and Gaido, K.W. (2000). Toxicol. Sci.

    Organophosphate insecticides represent one of the most widely used classes of pesticide...

  1. Exposures of children to organophosphate pesticides and their potential adverse health effects.

    PubMed Central

    Eskenazi, B; Bradman, A; Castorina, R

    1999-01-01

    Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children

  2. Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children

    PubMed Central

    Bouchard, Maryse F.; Chevrier, Jonathan; Harley, Kim G.; Kogut, Katherine; Vedar, Michelle; Calderon, Norma; Trujillo, Celina; Johnson, Caroline; Bradman, Asa; Barr, Dana Boyd

    2011-01-01

    Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development. Objective: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children. Methods: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment. Results: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores. Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population. PMID:21507776

  3. Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children.

    PubMed

    Yu, C-J; Du, J-C; Chiou, H-C; Chung, M-Y; Yang, W; Chen, Y-S; Fuh, M-R; Chien, L-C; Hwang, B; Chen, M-L

    2016-07-01

    Attention-deficit/hyperactivity disorder (ADHD) is male predominated, and the etiology of this disorder remains unclear. Past studies have assessed the association of low-level organophosphate pesticide exposure with childhood ADHD cross-sectionally and prospectively. However, the results have been inconsistent. A first case-control study was performed to investigate the relationship between organophosphate pesticide exposure and ADHD with adjusted covariates. We recruited 97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age. Exposure was assessed using urinary levels of dialkylphosphate metabolites, which are biomarkers of OP pesticide exposure. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. The sociodemographics and lifestyles of the children and of the mothers during pregnancy were collected using a questionnaire. The blood lead levels of both groups were similar (1.57 ± 0.73 vs. 1.73 ± 0.77 μg/dL, p = 0.15). Significant urinary concentration differences in one of the six dialkylphosphate metabolites, dimethylphosphate (DMP), were found between ADHD and control subjects (322.92 ± 315.68 vs. 224.37 ± 156.58 nmol/g cr., p < 0.01). A dose-response relationship was found between urinary concentrations of DMP and ADHD in both crude and adjusted analyses (p for trend<0.05). Children with higher urinary DMP concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD. We report a dose-response relationship between child DMP levels and ADHD. Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD. © 2016 American Society of Andrology and European Academy of Andrology.

  4. Assessing joint toxicity of four organophosphate and carbamate insecticides in common carp (Cyprinus carpio) using acetylcholinesterase activity as an endpoint.

    PubMed

    Wang, Yanhua; Chen, Chen; Zhao, Xueping; Wang, Qiang; Qian, Yongzhong

    2015-07-01

    Mixtures of organophosphate (OP) and carbamate (CB) pesticides are commonly detected in freshwater ecosystems. These pesticides inhibit the activity of acetylcholinesterase (AChE) and have potential to interfere with behaviors that may be essential for the survival of species. Although the effects of individual anticholinesterase insecticides on aquatic species have been studied for decades, the neurotoxicity of mixtures is still poorly understood. In the present study, brain AChE inhibition in carp (Cyprinus carpio) exposed to a series of concentrations of the organophosphates (malathion and triazophos) as well as the carbamates (fenobucarb and carbosulfan) was measured. In equitoxic mixtures, the observed AChE activity inhibition of the malathion plus triazophos, and triazophos plus carbosulfan mixtures, was synergism. In equivalent concentration mixtures, the combination of malathion plus fenobucarb mixture conformed to synergism, while the observed AChE activity inhibition of the remaining pairings was less than additive. Single pesticide risk assessments are likely to underestimate the impacts of these insecticides on carps in aquatic environment where mixtures occur. Moreover, mixtures of pesticides that have been commonly reported in aquatic ecosystems may pose a more important challenge than previously anticipated. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Electroencephalogram, cognitive state, psychological disorders, clinical symptom, and oxidative stress in horticulture farmers exposed to organophosphate pesticides.

    PubMed

    Bayrami, Mansour; Hashemi, Touraj; Malekirad, Ali Akbar; Ashayeri, Hassan; Faraji, Fardin; Abdollahi, Mohammad

    2012-02-01

    The aim of this paper was to study the toxicity of organophosphate (OP) pesticides in exposed farmers for electroencephalography, cognitive state, psychological disorders, clinical symptom, oxidative stress, acetylcholinesterase, and DNA damage. A comparative cross-sectional analysis was carried out in 40 horticulture farmers who were exposed to OPs in comparison to a control group containing 40 healthy subjects with the same age and sex and education level. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase, glutathione peroxidase, DNA damage, total antioxidant capacity (TAC), total thiol molecules, and acetylcholinesterase (AChE) activity were measured in the blood of subjects. Clinical examination and complete blood test were undertaken in order to record any abnormal sign or symptoms. Cognitive function, psychological symptoms, and psychological distress were examined and recorded. Comparing with controls, the farmers showed higher blood levels of SOD and LPO while their TAC decreased. Farmers showed clinical symptoms such as eczema, breathing muscle weakness, nausea, and saliva secretion. Regarding cognitive function, the orientation, registration, attention and calculation, recall, and language were not significantly different in farmers and controls. Among examinations for psychological distress, only labeled somatization was significantly higher in farmers. The present findings indicate that oxidative stress and inhibition of AChE can be seen in chronically OP-exposed people but incidence of neuropsychological disorders seems a complex multivariate phenomenon that might be seen in long-term high-dose exposure situations. Use of supplementary antioxidants would be useful in the treatment of farmers.

  6. PON1 and Neurodevelopment in Children from the CHAMACOS Study Exposed to Organophosphate Pesticides in Utero

    PubMed Central

    Eskenazi, Brenda; Huen, Karen; Marks, Amy; Harley, Kim G.; Bradman, Asa; Barr, Dana Boyd; Holland, Nina

    2010-01-01

    Background Paraoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. Objective We determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior. Methods We measured DAP concentrations in maternal urine during pregnancy, PON1192 and PON1−108 genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds’ blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD. Results Children with the PON1−108T allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1−108T allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant. Conclusion PON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure. PMID:21126941

  7. Engineering Pseudomonas putida KT2440 for simultaneous degradation of organophosphates and pyrethroids and its application in bioremediation of soil.

    PubMed

    Zuo, Zhenqiang; Gong, Ting; Che, You; Liu, Ruihua; Xu, Ping; Jiang, Hong; Qiao, Chuanling; Song, Cunjiang; Yang, Chao

    2015-06-01

    Agricultural soils are usually co-contaminated with organophosphate (OP) and pyrethroid pesticides. To develop a stable and marker-free Pseudomonas putida for co-expression of two pesticide-degrading enzymes, we constructed a suicide plasmid with expression cassettes containing a constitutive promoter J23119, an OP-degrading gene (mpd), a pyrethroid-hydrolyzing carboxylesterase gene (pytH) that utilizes the upp gene as a counter-selectable marker for upp-deficient P. putida. By introduction of suicide plasmid and two-step homologous recombination, both mpd and pytH genes were integrated into the chromosome of a robust soil bacterium P. putida KT2440 and no selection marker was left on chromosome. Functional expression of mpd and pytH in P. putida KT2440 was demonstrated by Western blot analysis and enzyme activity assays. Degradation experiments with liquid cultures showed that the mixed pesticides including methyl parathion, fenitrothion, chlorpyrifos, permethrin, fenpropathrin, and cypermethrin (0.2 mM each) were degraded completely within 48 h. The inoculation of engineered strain (10(6) cells/g) to soils treated with the above mixed pesticides resulted in a higher degradation rate than in noninoculated soils. All six pesticides could be degraded completely within 15 days in fumigated and nonfumigated soils with inoculation. Theses results highlight the potential of the engineered strain to be used for in situ bioremediation of soils co-contaminated with OP and pyrethroid pesticides.

  8. Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community: a case study from the CHAMACOS cohort.

    PubMed Central

    Castorina, Rosemary; Bradman, Asa; McKone, Thomas E; Barr, Dana B; Harnly, Martha E; Eskenazi, Brenda

    2003-01-01

    Approximately 230,000 kg of organophosphate (OP) pesticides are applied annually in California's Salinas Valley. These activities have raised concerns about exposures to area residents. We collected three spot urine samples from pregnant women (between 1999 and 2001) enrolled in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort study, and analyzed them for six dialkyl phosphate metabolites. We used urine from 446 pregnant women to estimate OP pesticide doses with two deterministic steady-state modeling methods: method 1, which assumed the metabolites were attributable entirely to a single diethyl or dimethyl OP pesticide; and method 2, which adapted U.S. Environmental Protection Agency (U.S. EPA) draft guidelines for cumulative risk assessment to estimate dose from a mixture of OP pesticides that share a common mechanism of toxicity. We used pesticide use reporting data for the Salinas Valley to approximate the mixture to which the women were exposed. Based on average OP pesticide dose estimates that assumed exposure to a single OP pesticide (method 1), between 0% and 36.1% of study participants' doses failed to attain a margin of exposure (MOE) of 100 relative to the U.S. EPA oral benchmark dose(10) (BMD(10)), depending on the assumption made about the parent compound. These BMD(10) values are doses expected to produce a 10% reduction in brain cholinesterase activity compared with background response in rats. Given the participants' average cumulative OP pesticide dose estimates (method 2) and regardless of the index chemical selected, we found that 14.8% of the doses failed to attain an MOE of 100 relative to the BMD(10) of the selected index. An uncertainty analysis of the pesticide mixture parameter, which is extrapolated from pesticide application data for the study area and not directly quantified for each individual, suggests that this point estimate could range from 1 to 34%. In future analyses, we

  9. New CeO2 nanoparticles-based topical formulations for the skin protection against organophosphates.

    PubMed

    Zenerino, Arnaud; Boutard, Tifenn; Bignon, Cécile; Amigoni, Sonia; Josse, Denis; Devers, Thierry; Guittard, Frédéric

    2015-01-01

    To reinforce skin protection against organophosphates (OPs), the development of new topical skin protectants (TSP) has received a great interest. Nanoparticles like cerium dioxide (CeO 2 ) known to adsorb and neutralize OPs are interesting candidates for TSP. However, NPs are difficult to disperse into formulations and they are suspected of toxicological issues. Thus, we want to study: (1) the effect of the addition of CeO 2 NPs in formulations for the skin protection (2) the impact of the doping of CeO 2 NPs by calcium; (3) the effect of two methods of dispersion of CeO 2 NPs: an O/W emulsion or a suspension of a fluorinated thickening polymer (HASE-F) grafted with these NPs. As a screening approach we used silicone membranes as a skin equivalent and Franz diffusion cells for permeation tests. The addition of pure CeO 2 NPs in both formulations permits the penetration to decrease by a 3-4-fold factor. The O/W emulsion allows is the best approach to obtain a film-forming coating with a good reproducibility of the penetration results; whereas the grafting of NPs to a thickener is the best way to obtain an efficient homogenous suspension of CeO 2 NPs with a decreased of toxicological impact but the coating is less film-forming which slightly impacts the reproducibility of the penetration results.

  10. Biodegradation of Organophosphate Chemical Warfare Agents by Activated Sludge

    DTIC Science & Technology

    2012-03-01

    Holmstedt, B. (1963). Structure- activity relationships of the organophosphorus anticholinesterase agents. In: Koelle, G.B. (ed.), Handbuch...BIODEGRADATION OF ORGANOPHOSPHATE CHEMICAL WARFARE AGENTS BY ACTIVATED SLUDGE Steven J. Schuldt...AFIT/GES/ENV/12-M04 BIODEGRADATION OF ORGANOPHOSPHATE CHEMICAL WARFARE AGENTS BY ACTIVATED SLUDGE THESIS Presented to the

  11. Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism and organophosphate detoxification

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nomura, Daniel K.; Fujioka, Kazutoshi; Issa, Roger S.

    2008-04-01

    Serine hydrolase KIAA1363 is an acetyl monoalkylglycerol ether (AcMAGE) hydrolase involved in tumor cell invasiveness. It is also an organophosphate (OP) insecticide-detoxifying enzyme. The key to understanding these dual properties was the use of KIAA1363 +/+ (wildtype) and -/- (gene deficient) mice to define the role of this enzyme in brain and other tissues and its effectiveness in vivo in reducing OP toxicity. KIAA1363 was the primary AcMAGE hydrolase in brain, lung, heart and kidney and was highly sensitive to inactivation by chlorpyrifos oxon (CPO) (IC{sub 50} 2 nM) [the bioactivated metabolite of the major insecticide chlorpyrifos (CPF)]. Although theremore » was no difference in hydrolysis product monoalkylglycerol ether (MAGE) levels in +/+ and -/- mouse brains in vivo, isopropyl dodecylfluorophosphonate (30 mg/kg) and CPF (100 mg/kg) resulted in 23-51% decrease in brain MAGE levels consistent with inhibition of AcMAGE hydrolase activity. On incubating +/+ and -/- brain membranes with AcMAGE and cytidine-5'-diphosphocholine, the absence of KIAA1363 activity dramatically increased de novo formation of platelet-activating factor (PAF) and lyso-PAF, signifying that metabolically-stabilized AcMAGE can be converted to this bioactive lipid in brain. On considering detoxification, KIAA1363 -/- mice were significantly more sensitive than +/+ mice to ip-administered CPF (100 mg/kg) and parathion (10 mg/kg) with increased tremoring and mortality that correlated for CPF with greater brain acetylcholinesterase inhibition. Docking AcMAGE and CPO in a KIAA1363 active site model showed similar positioning of their acetyl and trichloropyridinyl moieties, respectively. This study establishes the relevance of KIAA1363 in ether lipid metabolism and OP detoxification.« less

  12. Acute soman poisoning in primates neither pretreated nor receiving immediate therapy: value of gacyclidine (GK-11) in delayed medical support.

    PubMed

    Lallement, G; Clarençon, D; Galonnier, M; Baubichon, D; Burckhart, M F; Peoc'h, M

    1999-03-01

    Organophosphorus (OP) nerve agents are still used as warfare and terrorism compounds. Classical delayed treatment of victims of organophosphate poisoning includes combined i.v. administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). The objective of this study was to evaluate, in a realistic setting, the therapeutic benefit of administration of GK-11 (gacyclidine), an antiglutamatergic compound, as a complement to the above therapy against organophosphate poisoning. Gacyclidine was injected (i.v.) in combination with atropine/diazepam/pralidoxime at man-equivalent doses after a 45- or 30-min latency period to intoxicated primates (2 LD50). The effects of gacyclidine on the animals' survival, electroencephalographic (EEG) activity, signs of toxicity, recovery after challenge and central nervous system histology were examined. The present data demonstrated that atropine/diazepam/pralidoxime alone or combined with gacyclidine did not prevent signs of soman toxicity when treatment was delayed 45 min after poisoning. Atropine/diazepam/pralidoxime also did not control seizures or prevent neuropathology in primates exhibiting severe signs of poisoning when treatment was commenced 30 min after intoxication. However, in this latter case, EEG recordings revealed that additional treatment with gacyclidine was able to stop soman-induced seizures and restore normal EEG activity. This drug also totally prevented the neuropathology observed 5 weeks after soman exposure in animals treated with atropine/diazepam/pralidoxime alone. Overall, in the case of severe OP-poisoning, gacyclidine represents a promising adjuvant therapy to the currently available polymedication to ensure optimal management of organophosphate poisoning in man. This drug is presently being evaluated in a human clinical trial for a different neuroprotective indication. However, it should always be kept in

  13. Subacute developmental exposure of zebrafish to the organophosphate pesticide metabolite, chlorpyrifos-oxon, results in defects in Rohon-Beard sensory neuron development

    PubMed Central

    Jacobson, Saskia M.; Birkholz, Denise A.; McNamara, Marcy L.; Bharate, Sandip B.; George, Kathleen M.

    2010-01-01

    Organophosphate pesticides (OPs) are environmental toxicants known to inhibit the catalytic activity of acetylcholinesterase (AChE) resulting in hypercholinergic toxicity symptoms. In developing embryos, OPs have been hypothesized to affect both cholinergic and non-cholinergic pathways. In order to understand the neurological pathways affected by OP exposure during embryogenesis, we developed a subacute model of OP developmental exposure in zebrafish by exposing embryos to a dose of the OP metabolite chlorpyrifos oxon (CPO) that is non-lethal and significantly inhibited AChE enzymatic activity compared to control embryos (43% at 1 day post-fertilization (dpf) and 11% at 2 dpf). Phenotypic analysis of CPO-exposed embryos demonstrated that embryonic growth, as analyzed by gross morphology, was normal in 85% of treated embryos. Muscle fiber formation was similar to control embryos as analyzed by birefringence, and nicotinic acetylcholine receptor (nAChR) cluster formation was quantitatively similar to control embryos as analyzed by α-bungarotoxin staining. These results indicate that partial AChE activity during the early days of zebrafish development is sufficient for general development, muscle fiber, and nAChR development. Rohon-Beard (RB) sensory neurons exhibited aberrant peripheral axon extension and gene expression profiling suggests that several genes responsible for RB neurogenesis are down-regulated. Stability of CPO in egg water at 28.5 °C was determined by HPLC-UV-MS analysis which revealed that the CPO concentration used in our studies hydrolyzes in egg water with a half-life of one day. The result that developmental CPO exposure affected RB neurogenesis without affecting muscle fiber or nAChR cluster formation demonstrates that zebrafish are a strong model system for characterizing subtle neurological pathologies resulting from environmental toxicants. PMID:20701988

  14. Structure-Based and Random Mutagenesis Approaches Increase the Organophosphate-Degrading Activity of a Phosphotriesterase Homologue from Deinococcus radiodurans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hawwa, Renda; Larsen, Sonia D.; Ratia, Kiira

    2010-11-09

    An enzyme from the amidohydrolase family from Deinococcus radiodurans (Dr-OPH) with homology to phosphotriesterase has been shown to exhibit activity against both organophosphate (OP) and lactone compounds. We have characterized the physical properties of Dr-OPH and have found it to be a highly thermostable enzyme, remaining active after 3 h of incubation at 60 C and withstanding incubation at temperatures up to 70 C. In addition, it can withstand concentrations of at least 200 mg/mL. These properties make Dr-OPH a promising candidate for development in commercial applications. However, compared to the most widely studied OP-degrading enzyme, that from Pseudomonas diminuta,more » Dr-OPH has low hydrolytic activity against certain OP substrates. Therefore, we sought to improve the OP-degrading activity of Dr-OPH, specifically toward the pesticides ethyl and methyl paraoxon, using structure-based and random approaches. Site-directed mutagenesis, random mutagenesis, and site-saturation mutagenesis were utilized to increase the OP-degrading activity of Dr-OPH. Out of a screen of more than 30,000 potential mutants, a total of 26 mutant enzymes were purified and characterized kinetically. Crystal structures of w.t. Dr-OPH, of Dr-OPH in complex with a product analog, and of 7 mutant enzymes were determined to resolutions between 1.7 and 2.4 {angstrom}. Information from these structures directed the design and production of 4 additional mutants for analysis. In total, our mutagenesis efforts improved the catalytic activity of Dr-OPH toward ethyl and methyl paraoxon by 126- and 322-fold and raised the specificity for these two substrates by 557- and 183-fold, respectively. Our work highlights the importance of an iterative approach to mutagenesis, proving that large rate enhancements are achieved when mutations are made in already active mutants. In addition, the relationship between the kinetic parameters and the introduced mutations has allowed us to hypothesize on

  15. Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children

    PubMed Central

    Eskenazi, Brenda; Marks, Amy R.; Bradman, Asa; Harley, Kim; Barr, Dana B.; Johnson, Caroline; Morga, Norma; Jewell, Nicholas P.

    2007-01-01

    Background Organophosphate (OP) pesticides are widely used in agriculture and homes. Animal studies suggest that even moderate doses are neurodevelopmental toxicants, but there are few studies in humans. Objectives We investigated the relationship of prenatal and child OP urinary metabolite levels with children’s neurodevelopment. Methods Participating children were from a longitudinal birth cohort of primarily Latino farm-worker families in California. We measured six nonspecific dialkylphosphate (DAP) metabolites in maternal and child urine as well as metabolites specific to malathion (MDA) and chlorpyrifos (TCPy) in maternal urine. We examined their association with children’s performance at 6 (n = 396), 12 (n = 395), and 24 (n = 372) months of age on the Bayley Scales of Infant Development [Mental Development (MDI) and Psychomotor Development (PDI) Indices] and mother’s report on the Child Behavior Checklist (CBCL) (n = 356). Results Generally, pregnancy DAP levels were negatively associated with MDI, but child measures were positively associated. At 24 months of age, these associations reached statistical significance [per 10-fold increase in prenatal DAPs: β = −3.5 points; 95% confidence interval (CI), −6.6 to −0.5; child DAPs: β = 2.4 points; 95% CI, 0.5 to 4.2]. Neither prenatal nor child DAPs were associated with PDI or CBCL attention problems, but both prenatal and postnatal DAPs were associated with risk of pervasive developmental disorder [per 10-fold increase in prenatal DAPs: odds ratio (OR) = 2.3, p = 0.05; child DAPs OR = 1.7, p = 0.04]. MDA and TCPy were not associated with any outcome. Conclusions We report adverse associations of prenatal DAPs with mental development and pervasive developmental problems at 24 months of age. Results should be interpreted with caution given the observed positive relationship with postnatal DAPs. PMID:17520070

  16. Chemotaxis and degradation of organophosphate compound by a novel moderately thermo-halo tolerant Pseudomonas sp. strain BUR11: evidence for possible existence of two pathways for degradation.

    PubMed

    Pailan, Santanu; Saha, Pradipta

    2015-01-01

    An organophosphate (OP) degrading chemotactic bacterial strain BUR11 isolated from an agricultural field was identified as a member of Pseudomonas genus on the basis of its 16S rRNA gene sequence. The strain could utilize parathion, chlorpyrifos and their major hydrolytic intermediates as sole source of carbon for its growth and exhibited positive chemotactic response towards most of them. Optimum concentration of parathion for its growth was recorded to be 200 ppm and 62% of which was degraded within 96 h at 37 °C. Growth studies indicated the strain to be moderately thermo-halo tolerant in nature. Investigation based on identification of intermediates of parathion degradation by thin layer chromatography (TLC), high performance liquid chromatography (HPLC), gas chromatography (GC) and liquid chromatography mass spectrometry (LC-MS/MS) provided evidence for possible existence of two pathways. The first pathway proceeds via 4-nitrophenol (4-NP) while the second proceeds through formation of 4-aminoparathion (4-APar), 4-aminophenol (4-AP) and parabenzoquinone (PBQ). This is the first report of chemotaxis towards organophosphate compound by a thermo-halo tolerant bacterium.

  17. Chemotaxis and degradation of organophosphate compound by a novel moderately thermo-halo tolerant Pseudomonas sp. strain BUR11: evidence for possible existence of two pathways for degradation

    PubMed Central

    Pailan, Santanu

    2015-01-01

    An organophosphate (OP) degrading chemotactic bacterial strain BUR11 isolated from an agricultural field was identified as a member of Pseudomonas genus on the basis of its 16S rRNA gene sequence. The strain could utilize parathion, chlorpyrifos and their major hydrolytic intermediates as sole source of carbon for its growth and exhibited positive chemotactic response towards most of them. Optimum concentration of parathion for its growth was recorded to be 200 ppm and 62% of which was degraded within 96 h at 37 °C. Growth studies indicated the strain to be moderately thermo-halo tolerant in nature. Investigation based on identification of intermediates of parathion degradation by thin layer chromatography (TLC), high performance liquid chromatography (HPLC), gas chromatography (GC) and liquid chromatography mass spectrometry (LC-MS/MS) provided evidence for possible existence of two pathways. The first pathway proceeds via 4-nitrophenol (4-NP) while the second proceeds through formation of 4-aminoparathion (4-APar), 4-aminophenol (4-AP) and parabenzoquinone (PBQ). This is the first report of chemotaxis towards organophosphate compound by a thermo-halo tolerant bacterium. PMID:26587344

  18. Environmentally relevant organophosphate triesters in herring gulls: In vitro biotransformation and kinetics and diester metabolite formation using a hepatic microsomal assay.

    PubMed

    Greaves, Alana K; Su, Guanyong; Letcher, Robert J

    2016-10-01

    The in vitro biotransformation and kinetics of six organophosphate triester (OPE) flame retardants were investigated in herring gulls (Larus argentatus) from the Great Lakes using a hepatic microsomal metabolism assay. Administration of each individual OPE (tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), triethyl phosphate (TEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP)) to the in vitro assay (concentration range 0.01 to 10μM) resulted in rapid depletion with the exception of TEP. Following the Michaelis-Menten enzyme kinetics model, a preliminary 2-minute incubation period was used to estimate the Vmax (±SE) values (i.e., the maximal rate of reaction for a saturated enzyme system), which ranged from 5.0±0.4 (TPHP) to 29±18pmol/min/mg protein (TBOEP), as well as the KM (±SE) values (i.e., the OPE concentration corresponding to one half of the Vmax), which ranged from 9.8±1 (TPHP) to 189±135nM (TBOEP). Biotransformation assays over a 100-minute incubation period revealed that TNBP was metabolized most rapidly (with a depletion rate of 73±4pmol/min/mg protein), followed by TBOEP (53±8pmol/min/mg), TCIPP (27±1pmol/min/mg), TPHP (22±2pmol/min/mg) and TDCIPP (8±1pmol/min/mg). In vitro biotransformation of OP triesters was clearly structure-dependent where non-halogenated alkyl OP triesters were metabolized more rapidly than halogenated alkyl triesters. Halogenated OP triesters were transformed to their respective diesters more efficiently relative to non-halogenated OP triesters. To our knowledge, this is the first study to investigate OP triester metabolism and OP diester formation in an avian or wildlife model system, which is important to understand the fate and biological activity of OPEs in an exposed organism. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Environmentally relevant organophosphate triesters in herring gulls: In vitro biotransformation and kinetics and diester metabolite formation using a hepatic microsomal assay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Greaves, Alana K.

    The in vitro biotransformation and kinetics of six organophosphate triester (OPE) flame retardants were investigated in herring gulls (Larus argentatus) from the Great Lakes using a hepatic microsomal metabolism assay. Administration of each individual OPE (tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), triethyl phosphate (TEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP)) to the in vitro assay (concentration range 0.01 to 10 μM) resulted in rapid depletion with the exception of TEP. Following the Michaelis-Menten enzyme kinetics model, a preliminary 2-minute incubation period was used to estimate the V{sub max} (± SE) values (i.e., the maximal rate ofmore » reaction for a saturated enzyme system), which ranged from 5.0 ± 0.4 (TPHP) to 29 ± 18 pmol/min/mg protein (TBOEP), as well as the K{sub M} (± SE) values (i.e., the OPE concentration corresponding to one half of the V{sub max}), which ranged from 9.8 ± 1 (TPHP) to 189 ± 135 nM (TBOEP). Biotransformation assays over a 100-minute incubation period revealed that TNBP was metabolized most rapidly (with a depletion rate of 73 ± 4 pmol/min/mg protein), followed by TBOEP (53 ± 8 pmol/min/mg), TCIPP (27 ± 1 pmol/min/mg), TPHP (22 ± 2 pmol/min/mg) and TDCIPP (8 ± 1 pmol/min/mg). In vitro biotransformation of OP triesters was clearly structure-dependent where non-halogenated alkyl OP triesters were metabolized more rapidly than halogenated alkyl triesters. Halogenated OP triesters were transformed to their respective diesters more efficiently relative to non-halogenated OP triesters. To our knowledge, this is the first study to investigate OP triester metabolism and OP diester formation in an avian or wildlife model system, which is important to understand the fate and biological activity of OPEs in an exposed organism. - Highlights: • The metabolism and kinetics of 6 OPEs were examined in herring gull liver

  20. A single method for detecting 11 organophosphate pesticides in human plasma and breastmilk using GC-FPD

    PubMed Central

    Naksen, Warangkana; Prapamontol, Tippawan; Mangklabruks, Ampica; Chantara, Somporn; Thavornyutikarn, Prasak; Robson, Mark G.; Ryan, P. Barry; Barr, Dana Boyd; Panuwet, Parinya

    2016-01-01

    Organophosphate (OP) pesticides are widely used for crop protection in many countries including Thailand. Aside from causing environmental contamination, they affect human health especially by over-stimulating of the neurotransmission system. OP pesticides, as with other non-persistent pesticides, degrade quickly in the environment as well as are metabolized quite rapidly in humans. Assessing human exposures to these compounds requires analytical methods that are sensitive, robust, and most importantly, suitable for specific laboratory settings. The aim of this study was to develop and validate an analytical method for measuring 11 OP pesticide residues in human plasma and breast milk. Analytes in both plasma and breast milk samples were extracted with acetone and methylene chloride, cleaned-up using aminopropyl solid phase extraction cartridges, and analyzed by gas chromatography with flame photometric detection. The optimized method exhibited good linearity, with the coefficients of determination of 0.996–0.999 and <7% error about the slope. Extraction recoveries from spiked plasma and breast milk samples at low and medium concentrations (0.8–5.0 and 1.6–10 ng mL−1, respectively) ranged from 59.4 % (ethion) to 94.0 % (chlorpyrifos). Intra-batch and inter-batch precisions ranged from 2.3–18.9% and 5.8–19.5%, respectively. Method detection limits of plasma and breast milk ranged from 0.18–1.36 and 0.09–2.66 ng mL−1, respectively. We analyzed 63 plasma and 30 breastmilk samples collected from farmworkers in Chiang Mai Province to determine the suitability of this method for occupational exposure assessment. Of the 11 pesticides measured, seven were detected in plasma samples and five were detected in breast milk samples. Mass spectrometry was used to confirm results. Overall, this method is rapid and reliable. It offers the laboratories with limited access to mass spectrometry a capacity to investigate levels OP pesticides in plasma and breastmilk

  1. Pediatric Susceptibility to Nerve Agent-Induced Seizures and Effectiveness of Anticonvulsant Treatments

    DTIC Science & Technology

    2014-12-01

    poisoning can result in status epilepticus (SE), which can become pharmacoresistant if treatment is delayed. Virtually no data exist on OP-induced...are needed to characterize models of P7 and P14 DFP-induced SE. 15. SUBJECT TERMS Status Epilepticus , seizure, organophosphate, DFP, pediatric...5 Introduction Organophosphate (OP) exposure can lead to continuous, repetitive seizures (i.e., status epilepticus , SE), which are

  2. Study of commonly used organophosphate pesticides that induced oxidative stress and apoptosis in peripheral blood lymphocytes of rats.

    PubMed

    Ojha, A; Gupta, Y K

    2017-11-01

    In a previous study, we have found that organophosphate (OP) pesticides such as chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) significantly induced genotoxicity in peripheral blood lymphocytes of rats. To explore the mechanism of OP-induced genotoxicity, we measured the formation of DNA interstrand cross-links (DICs) and apoptosis in peripheral blood lymphocytes of rats. Peripheral blood lymphocytes of rats were treated with CPF, MPT, and MLT individually and in combination at concentrations of 0.1 and 0.25 LC 50 for 2, 4, 8, and 12 h at 37°C. Lipid peroxidation (LPO) was measured as a biomarker of oxidative stress. Apoptosis induced by CPF, MPT, and MLT individually and in combination was determined by measuring the intracellular level of active caspase-3 and caspase-9 by spectrofluorimetry. We found significant dose- and time-dependent increases in LPO, DICs formation and increase of intracellular active caspase-3 and caspase-9 in exposed peripheral blood lymphocytes of rats. These findings suggest that the studied pesticides have potential to induce oxidative stress, cause DNA adduct formation, and cause failure of adduct repair, which leads to apoptosis that is partially mediated by activation of intracellular caspase-3 and caspase-9.

  3. Structural Characterization and Reversal of the Natural Organophosphate Resistance of a D-Type Esterase, Saccharomyces cerevisiae S-Formylglutathione Hydrolase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Legler,P.; Kumaran, D.; Swaminathan, S.

    2008-01-01

    Saccharomyces cerevisiae expresses a 67.8 kDa homodimeric serine thioesterase, S-formylglutathione hydrolase (SFGH), that is 39.9% identical with human esterase D. Both enzymes possess significant carboxylesterase and S-formylglutathione thioesterase activity but are unusually resistant to organophosphate (OP) inhibitors. We determined the X-ray crystal structure of yeast (y) SFGH to 2.3 Angstroms resolution by multiwavelength anomalous dispersion and used the structure to guide site-specific mutagenesis experiments addressing substrate and inhibitor reactivity. Our results demonstrate a steric mechanism of OP resistance mediated by a single indole ring (W197) located in an enzyme 'acyl pocket'. The W197I substitution enhances ySFGH reactivity with paraoxon bymore » >1000-fold (kiW197I = 16 {+-} 2 mM-1 h-1), thereby overcoming natural OP resistance. W197I increases the rate of OP inhibition under pseudo-first-order conditions but does not accelerate OP hydrolysis. The structure of the paraoxon-inhibited W197I variant was determined by molecular replacement (2.2 Angstroms); it revealed a stabilized sulfenic acid at Cys60. Wild-type (WT) ySFGH is inhibited by thiol reactive compounds and is sensitive to oxidation; thus, the cysteine sulfenic acid may play a role in the regulation of a 'D-type' esterase. The structure of the W197I variant is the first reported cysteine sulfenic acid in a serine esterase. We constructed five Cys60/W197I variants and show that introducing a positive charge near the oxyanion hole, W197I/C60R or W197I/C60K, results in a further enhancement of the rates of phosphorylation with paraoxon (ki = 42 or 80 mM-1 h-1, respectively) but does not affect the dephosphorylation of the enzyme. We also characterized three histidine substitutions near the oxyanion hole, G57H, L58H, and M162H, which significantly decrease esterase activity.« less

  4. Scenario of organophosphate pollution and toxicity in India: A review.

    PubMed

    Kumar, Shardendu; Kaushik, Garima; Villarreal-Chiu, Juan Francisco

    2016-05-01

    The present study on organophosphate deals with the reports on pollution and toxicity cases throughout India. The use of pesticides was introduced in India during the 1960s which are now being used on a large scale and represents the common feature of Indian agriculture. Use of organophosphates as a pesticide came as an alternative to chlorinated hydrocarbons due to their easy degradability. Although these xenobiotics degrade under natural condition, their residues have been detected in soil, sediments, and water due to their non-regulated usage practice. The over-reliance on pesticides has not only threatened our environment but contaminations of organophosphate residues have been also detected in certain agricultural products like tea, sugars, vegetables, and fruits throughout India. This paper highlights many of the cases where different organophosphates have been detected exceeding their respective MRL values. Some organophosphates detected are so hazardous that even WHO has listed them in class 1a and class 1b hazardous group. Presence of their residues in blood, milk, honey, and tissues of human and animals revealed their excessive use and bioaccumulating capabilities. Their intentional or unintentional uptake is causing thousands of deaths and severity each year. Most of the toxicity cases presented here are due to their uptake during a suicidal attempt. This shows how easily these harmful substances are available in the market.

  5. Age-related differences in acute neurotoxicity produced by mevinphos, monocrotophos, dicrotophos, and phosphamidon.

    PubMed

    Moser, Virginia C

    2011-01-01

    Age-related differences in the acute neurotoxicity of cholinesterase (ChE)-inhibiting pesticides have been well-studied for a few organophosphates, but not for many others. In this study, we directly compared dose-responses using brain and red blood cell (RBC) ChE measurements, along with motor activity, for mevinphos, monocrotophos, dicrotophos, and phosphamidon. Long-Evans hooded male rats were tested as adults and at postnatal day (PND) 17; PND11 pups were also tested with dicrotophos only. All chemicals were administered via oral gavage and tests were conducted at times intended to span peak behavioral and ChE effects. All OPs tested produced a rapid onset and recovery from the behavioral effects. There were age-related differences in the inhibition of brain, but not necessarily RBC, ChE. Mevinphos was clearly more toxic, up to 4-fold, to the young rat. On the other hand, monocrotophos, dicrotophos, and phosphamidon were somewhat more toxic to the young rat, but the magnitude of the differences was < 2-fold lower. Motor activity was consistently decreased in adults for all chemicals tested; however, there was more variability with the pups and clear age-related differences were only observed for mevinphos. These data show that three of these four OPs were only moderately more toxic in young rats, and further support findings that age-related differences in pesticide toxicity are chemical-specific. Published by Elsevier Inc.

  6. Oxidative stress resulting from exposure of a human salivary gland cells to paraoxon: an in vitro model for organophosphate oral exposure.

    PubMed

    Prins, John M; Chao, Chih-Kai; Jacobson, Saskia M; Thompson, Charles M; George, Kathleen M

    2014-08-01

    Organophosphate (OP) compounds are used as insecticides, acaricides, and chemical agents and share a common neurotoxic mechanism of action. The biochemical alterations leading to many of the deleterious effects have been studied in neuronal cell lines, however, non-neuronal toxic effects of OPs are far less well characterized in vitro, and specifically in cell lines representing oral routes of exposure. To address this void, the human salivary gland (HSG) cell line, representing likely interactions in the oral cavity, was exposed to the representative OP paraoxon (PX; O,O-diethyl-p-nitrophenoxy phosphate) over a range of concentrations (0.01-100 μM) and analyzed for cytotoxicity. PX induced cytotoxicity in HSG cells at most of the exposure concentrations as revealed by MTT assay, however, the release of LDH only occurred at the highest concentration of PX tested (100 μM) at 48 h. Slight increases in cellular ATP levels were measured in PX-exposed (10 μM) HSG cells at 24 h. Exposing HSG cells to 10 μM PX also led to an increase in DNA fragmentation prior to loss of cellular membrane integrity implicating reactive oxygen species (ROS) as a trigger of toxicity. The ROS genes gss, gstm2, gstt2 and sod2 were upregulated, and the presence of superoxide following 10 μM PX exposure was determined via dihydroethidium fluorescence studies further implicating PX-induced oxidative stress in HSG cells. Published by Elsevier Ltd.

  7. Pediatric Susceptibility to Nerve Agent-Induced Seizures and Effectiveness of Anticonvulsant Treatments

    DTIC Science & Technology

    2013-10-01

    SUPPLEMENTARY NOTES 14. ABSTRACT Organophosphate (OP) poisoning can result in status epilepticus (SE), a medical emergency which can become...Introduction Organophosphate (OP) poisoning can result in status epilepticus (SE), a medical emergency which can become pharmacoresistant if...P28 rat pups. Figure 1. DFP-induced status epilepticus in a P28 rat. Animals were treated with 0.026 mg/kg pyridostigmine bromide (i.p.) 30 min

  8. The influence of organophosphate and carbamate on sperm chromatin and reproductive hormones among pesticide sprayers.

    PubMed

    Jamal, Farrukh; Haque, Quazi S; Singh, Sangram; Rastogi, S K

    2016-08-01

    This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes. © The Author(s) 2015.

  9. A case report of motor neuron disease in a patient showing significant level of DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane and toluene in blood.

    PubMed

    Kanavouras, Konstantinos; Tzatzarakis, Manolis N; Mastorodemos, Vasileios; Plaitakis, Andreas; Tsatsakis, Aristidis M

    2011-11-01

    Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology. Several epidemiological studies have suggested that occupational exposure to chemicals may be associated with disease pathogenesis. We report the case of a patient developing progressive motor neuron disease, who was chronically exposed to pesticides and organic solvents. The patient presented with leg spasticity and developed gradually clinical signs suggestive of amyotrophic lateral sclerosis, which was supported by the neurophysiologic and radiological findings. Our report is an evidence based case of combined exposure to organochlorine (DDTs), organophosphate pesticides (OPs) and organic solvents as confirmed by laboratory analysis in samples of blood and hair confirming systematic exposure. The concentration of non-specific dialkylphosphates metabolites (DAPs) of OPs in hair (dimethyphopshate (DMP) 1289.4 pg/mg and diethylphosphate (DEP) 709.4 pg/mg) and of DDTs (opDDE 484.0 pg/mg, ppDDE 526.6 pg/mg, opDDD 448.4 pg/mg, ppDDD+opDDT 259.9 pg/mg and ppDDT 573.7 pg/mg) were considerably significant. Toluene and n-hexane were also detected in blood on admission at hospital and quantified (1.23 and 0.87 μg/l, respectively), while 3 months after hospitalization blood testing was found negative for toluene and n-hexane and hair analysis was provided decrease levels of HCHs, DDTs and DAPs. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Therapeutic efficacy of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) against organophosphate intoxication.

    PubMed

    Bueters, Tjerk J H; Groen, Bas; Danhof, Meindert; IJzerman, Ad P; Van Helden, Herman P M

    2002-11-01

    The objective of the present study was to investigate whether reduction of central acetylcholine (ACh) accumulation by adenosine receptor agonists could serve as a generic treatment against organophosphate (OP) poisoning. The OPs studied were tabun ( O-ethyl- N-dimethylphosphoramidocyanidate), sarin (isopropylmethylphosphonofluoridate), VX ( O-ethyl- S-2-diisopropylaminoethylmethylphosphonothiolate) and parathion ( O, O-diethyl- O-(4-nitrophenyl)phosphorothioate). The efficacy of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) against an OP intoxication was examined on the basis of the occurrence of clinical symptoms that are directly associated with such intoxication. CPA (1-2 mg/kg) effectively attenuated the cholinergic symptoms and prevented mortality in lethally tabun- or sarin-intoxicated rats. In contrast, CPA (2 mg/kg) proved to be ineffective against VX or parathion intoxication. Intracerebral microdialysis studies revealed that survival of sarin-poisoned and CPA-treated animals coincided with a minor elevation of extracellular ACh concentrations in the brain relative to the baseline value, whereas an 11-fold increase in transmitter levels was observed in animals not treated with CPA. In VX-intoxicated rats, however, the ACh amounts increased 18-fold, irrespective of treatment with CPA. The striatal acetylcholinesterase (AChE) activity following a lethal sarin intoxication was completely abolished in the vehicle-treated animals, whereas 10% and 60% AChE activity remained in animals treated with 2 mg/kg CPA 1 min after or 2 min prior to the poisoning, respectively. In VX-intoxicated animals the AChE activity in the brain was strongly reduced (striatum 10%, hippocampus 1%) regardless of the CPA treatment. These results demonstrate that CPA is highly effective against tabun or sarin poisoning, but fails to protect against VX or parathion. Survival and attenuation of clinical signs in tabun- or sarin-poisoned animals are associated with a

  11. Pilot study on the combination of an organophosphate-based insecticide paint and pyrethroid-treated long lasting nets against pyrethroid resistant malaria vectors in Burkina Faso.

    PubMed

    Mosqueira, Beatriz; Soma, Dieudonné D; Namountougou, Moussa; Poda, Serge; Diabaté, Abdoulaye; Ali, Ouari; Fournet, Florence; Baldet, Thierry; Carnevale, Pierre; Dabiré, Roch K; Mas-Coma, Santiago

    2015-08-01

    A pilot study to test the efficacy of combining an organophosphate-based insecticide paint and pyrethroid-treated Long Lasting Insecticide Treated Nets (LLINs) against pyrethroid-resistant malaria vector mosquitoes was performed in a real village setting in Burkina Faso. Paint Inesfly 5A IGR™, comprised of two organophosphates (OPs) and an Insect Growth Regulator (IGR), was tested in combination with pyrethroid-treated LLINs. Efficacy was assessed in terms of mortality for 12 months using Early Morning Collections of malaria vectors and 30-minute WHO bioassays. Resistance to pyrethroids and OPs was assessed by detecting the frequency of L1014F and L1014S kdr mutations and Ace-1(R)G119S mutation, respectively. Blood meal origin was identified using a direct enzyme-linked immunosorbent assay (ELISA). The combination of Inesfly 5A IGR™ and LLINs was effective in killing 99.9-100% of malaria vector populations for 6 months regardless of the dose and volume treated. After 12 months, mortality rates decreased to 69.5-82.2%. The highest mortality rates observed in houses treated with 2 layers of insecticide paint and a larger volume. WHO bioassays supported these results: mortalities were 98.8-100% for 6 months and decreased after 12 months to 81.7-97.0%. Mortality rates in control houses with LLINs were low. Collected malaria vectors consisted exclusively of Anopheles coluzzii and were resistant to pyrethroids, with a L1014 kdr mutation frequency ranging from 60 to 98% through the study. About 58% of An. coluzzii collected inside houses had bloodfed on non-human animals. Combining Inesfly 5A IGR™ and LLINs yielded a one year killing efficacy against An. coluzzii highly resistant to pyrethroids but susceptible to OPs that exhibited an anthropo-zoophilic behaviour in the study area. The results obtained in a real setting supported previous work performed in experimental huts and underscore the need to study the impact that this novel strategy may have on clinical

  12. Inhalation Exposure of Organophosphate Pesticides by Vegetable Growers in the Bang-Rieng Subdistrict in Thailand

    PubMed Central

    Jaipieam, Somsiri; Visuthismajarn, Parichart; Siriwong, Wattasit; Borjan, Marija; Robson, Mark G.

    2009-01-01

    This study investigated inhalation exposure to organophosphate pesticides (OPPs) and evaluated the associated health risks to vegetable growers living in the Bang-Rieng agricultural community. Air samples were collected by using personal sampling pumps with sorbent tubes placed in the vegetable growers' breathing zone. Samples were collected during both wet and dry seasons. Residues of organophosphate pesticides, that is, chlorpyrifos, dicrotofos, and profenofos, were analyzed from 33 vegetable growers and 17 reference subjects. Results showed that median concentrations of OPPs in air in farm areas were in the range of 0.022–0.056 mg/m3 and air in nonfarm areas in the range of <0.0016–<0.005 mg/m3. The concentration of the three pesticides in the vegetable growers was significantly higher than that of the references during both seasons. The results also indicate that the vegetable growers may be at risk for acute adverse effects via the inhalation of chlorpyrifos and dicrotofos during pesticide application, mixing, loading, and spraying. It is suggested that authorities and the community should implement appropriate strategies concerning risk reduction and risk management. PMID:20168980

  13. Associations of maternal organophosphate pesticide exposure and PON1 activity with birth outcomes in SAWASDEE birth cohort, Thailand.

    PubMed

    Naksen, Warangkana; Prapamontol, Tippawan; Mangklabruks, Ampica; Chantara, Somporn; Thavornyutikarn, Prasak; Srinual, Niphan; Panuwet, Parinya; Ryan, P Barry; Riederer, Anne M; Barr, Dana Boyd

    2015-10-01

    Prenatal organophosphate (OP) pesticide exposure has been reported to be associated with adverse birth outcomes and neurodevelopment. However, the mechanisms of toxicity of OP pesticides on human fetal development have not yet been elucidated. Our pilot study birth cohort, the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE cohort) aimed to evaluate environmental chemical exposures and their relation to birth outcomes and infant neurodevelopment in 52 pregnant farmworkers in Fang district, Chiang Mai province, Thailand. A large array of data was collected multiple times during pregnancy including approximately monthly urine samples for evaluation of pesticide exposure, three blood samples for pesticide-related enzyme measurements and questionnaire data. This study investigated the changes in maternal acetylcholinesterase (AChE) and paraoxonase 1 (PON1) activities and their relation to urinary diakylphosphates (DAPs), class-related metabolites of OP pesticides, during pregnancy. Maternal AChE, butyrylcholinesterase (BChE) and PON1 activities were measured three times during pregnancy and urinary DAP concentrations were measured, on average, 8 times from enrollment during pregnancy until delivery. Among the individuals in the group with low maternal PON1 activity (n=23), newborn head circumference was negatively correlated with log10 maternal ∑DEAP and ∑DAP at enrollment (gestational age=12±3 weeks; β=-1.0 cm, p=0.03 and β=-1.8 cm, p<0.01, respectively) and at 32 weeks pregnancy (β=-1.1cm, p=0.04 and β=-2.6 cm, p=0.01, respectively). Furthermore, among these mothers, newborn birthweight was also negatively associated with log10 maternal ∑DEAP and ∑DAP at enrollment (β=-219.7 g, p=0.05 and β=-371.3g, p=0.02, respectively). Associations between maternal DAP levels and newborn outcomes were not observed in the group of participants with high maternal PON1 activity. Our results support previous findings from US birth

  14. Synthesis of reticulated hollow spheres structure NiCo2S4 and its application in organophosphate pesticides biosensor.

    PubMed

    Peng, Lei; Dong, Sheying; Wei, Wenbo; Yuan, Xiaojing; Huang, Tinglin

    2017-06-15

    Electrode materials play a key role in the development of electrochemical sensors, particularly enzyme-based biosensors. Here, a novel NiCo 2 S 4 with reticulated hollow spheres assembled from rod-like structures was prepared by a one-pot solvothermal method and its formation mechanism was discussed. Moreover, comparison of NiCo 2 S 4 materials from different experiment conditions as biosensors was investigated by electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV), and the best one that was reticulated hollow spheres assembled from rod-like structures NiCo 2 S 4 has been successfully employed as a matrix of AChE immobilization for the special structure, superior conductivity and rich reaction active sites. When using common two kinds of organophosphate pesticides (OPs) as model analyte, the biosensors demonstrated a wide linear range of 1.0×10 -12 -1.0×10 -8 gmL -1 with the detection limit of 4.2×10 -13 gmL -1 for methyl parathion, and 1.0×10 -13 -1.0×10 -10 gmL -1 with the detection limit of 3.5×10 -14 gmL -1 for paraoxon, respectively. The proposed biosensors exhibited many advantages such as acceptable stability and low cost, providing a promising tool for analysis of OPs. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Depression Prevalence and Exposure to Organophosphate Esters in Aircraft Maintenance Workers.

    PubMed

    Hardos, Jennifer E; Whitehead, Lawrence W; Han, Inkyu; Ott, Darrin K; Waller, D Kim

    2016-08-01

    Previous studies found that aircraft maintenance workers may be exposed to organophosphates in hydraulic fluid and engine oil. Studies have also illustrated a link between long-term low-level organophosphate pesticide exposure and depression. A questionnaire containing the Patient Health Questionnaire 8 depression screener was e-mailed to 52,080 aircraft maintenance workers (with N = 4801 complete responses) in a cross-sectional study to determine prevalence and severity of depression and descriptions of their occupational exposures. There was no significant difference between reported depression prevalence and severity in similar exposure groups in which aircraft maintenance workers were exposed or may have been exposed to organophosphate esters compared to similar exposure groups in which they were not exposed. However, a dichotomous measure of the prevalence of depression was significantly associated with self-reported exposure levels from low (OR: 1.21) to moderate (OR: 1.68) to high exposure (OR: 2.70) and with each exposure route including contact (OR: 1.68), inhalation (OR: 2.52), and ingestion (OR: 2.55). A self-reported four-level measure of depression severity was also associated with a self-reported four-level measure of exposure. Based on self-reported exposures and outcomes, an association is observed between organophosphate exposure and depression; however, we cannot assume that the associations we observed are causal because some workers may have been more likely to report exposure to organophosphate esters and also more likely to report depression. Future studies should consider using a larger sample size, better methods for characterizing crew chief exposures, and bioassays to measure dose rather than exposure. Hardos JE, Whitehead LW, Han I, Ott DK, Waller DK. Depression prevalence and exposure to organophosphate esters in aircraft maintenance workers. Aerosp Med Hum Perform. 2016; 87(8):712-717.

  16. Epidemiology of Organophosphate Poisoning in the Tshwane District of South Africa.

    PubMed

    Razwiedani, L L; Rautenbach, Pgd

    2017-01-01

    Organophosphate poisoning is a major public health problem in South Africa. Individuals get exposed to organophosphate in both the domestic and industrial spheres. A cross-sectional study was conducted using retrospective, secondary data of organophosphate poisoning cases over a 3-year period, reported at the Tshwane District surveillance office. Data were analysed using Microsoft Excel, and Epi Info version 7 was used for descriptive statistics. A total of 207 cases were reported with ages ranging from 10 months to 59 years. Most of the cases were men (58.9%). Intentional poisoning accounted for 51% of cases. Unintentional poisoning accounted for 21.7% of cases, and 26.5% of cases had unknown circumstances of poisoning. A significant number (50.2%) of intentional poisonings were suicide related. Nonsuicidal cases accounted for 47.4% of cases, and deliberate unlawful poisoning accounted for 2.4% of cases. The mortality rate for the whole group was 3.4%. Improvement in data collection on organophosphate poisoning is essential to properly measure the burden of the problem. More effective regulatory controls for pesticide use are needed in South Africa.

  17. Biomarkers of Exposure and Effect in Migrant Farmworker Children of Mexican Origin from Urban and Agricultural Regions of Texas

    EPA Science Inventory

    Some organophosphate pesticides (OPs) induce chromosome aberrations (CA) in experimental systems and may be genotoxic in persons exposed to home-use levels of OPs. However, the genotoxic effects of OPs have not been studied extensively in environmentally exposed children, such a...

  18. The effect of stress on the acute neurotoxicity of the organophosphate insecticide chlorpyrifos

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hancock, Sandra; Ehrich, Marion; Hinckley, Jonathan

    2007-03-15

    A study was conducted to determine if multiple exposures to several stress paradigms might affect the anticholinesterase effect of subsequently administered organophosphate insecticide chlorpyrifos. Male Sprague-Dawley rats were subject to daily periods of restraint, swimming, a combination of the two, or neither of the two (controls) (n = 8/group) for 5 days per week over a six-week period. The most profound stress, as measured by reduced body weight gain and elevated levels of plasma corticosterone, was swimming. On day 39 of the study, shortly after the daily stress episode, one half of the rats in each group was dosed withmore » 60 mg/kg chlorpyrifos subcutaneously. This had no effect on subsequent levels of plasma corticosterone. There were no stress-related differences in the degree of chlorpyrifos-induced inhibition of brain acetylcholinesterase in animals sacrificed on day 43.« less

  19. Paraoxonase 1 (PON1), agricultural organophosphate exposure, and Parkinson disease

    PubMed Central

    Manthripragada, Angelika D.; Costello, Sadie; Cockburn, Myles G.; Bronstein, Jeff M.; Ritz, Beate

    2011-01-01

    Background Human, animal and cell models support a role for pesticides in the etiology of Parkinson disease. Susceptibility to pesticides may be modified by genetic variants of xenobiotic enzymes, such as paraoxonase, that play a role in metabolizing some organophosphates. Methods We examined associations between Parkinson disease and the organophosphates diazinon, chlorpyrifos, and parathion, and the influence of a functional polymorphism at position 55 in the coding region of the PON1 gene (PON1-55). From 1 January 2001 through 1 January 2008, we recruited 351 incident cases and 363 controls from three rural California counties in a population-based case-control study. Participants provided a DNA sample, and residential exposure to organophosphates was determined from pesticide usage reports and a geographic information system (GIS) approach. We assessed the main effects of both genes and pesticides in unconditional logistic regression analyses, and evaluated the effect of carrying a PON1-55 MM variant on estimates of effects for diazinon, chlorpyrifos, and parathion exposures. Results Carriers of the variant MM PON1-55 genotype exposed to organophosphates exhibited a greater than 2-fold increase in Parkinson disease risk compared with persons who had the wildtype or heterozygous genotype and no exposure (for diazinon, odds ratio = 2.2 [95% confidence interval = 1.1–4.5]; for chlorpyrifos, 2.6 [1.3–5.4]). The effect estimate for chlorpyrifos, was more pronounced in younger-onset cases and controls (≤60 years) (5.3 [1.7–16]). No increase in risk was noted for parathion. Conclusion The increase in risk we observed among PON1-55 variant carriers for specific organophosphates metabolized by PON1 underscores the importance of considering susceptibility factors when studying environmental exposures in Parkinson disease. PMID:19907334

  20. Harnessing Nature’s Diversity: Discovering organophosphate bioscavenger characteristics among low molecular weight proteins

    PubMed Central

    Jacob, Reed B.; Michaels, Kenan C.; Anderson, Cathy J.; Fay, James M.; Dokholyan, Nikolay V.

    2016-01-01

    Organophosphate poisoning can occur from exposure to agricultural pesticides or chemical weapons. This exposure inhibits acetylcholinesterase resulting in increased acetylcholine levels within the synaptic cleft causing loss of muscle control, seizures, and death. Mitigating the effects of organophosphates in our bodies is critical and yet an unsolved challenge. Here, we present a computational strategy that integrates structure mining and modeling approaches, using which we identify novel candidates capable of interacting with a serine hydrolase probe (with equilibrium binding constants ranging from 4 to 120 μM). One candidate Smu. 1393c catalyzes the hydrolysis of the organophosphate omethoate (kcat/Km of (2.0 ± 1.3) × 10−1 M−1s−1) and paraoxon (kcat/Km of (4.6 ± 0.8) × 103 M−1s−1), V- and G-agent analogs respectively. In addition, Smu. 1393c protects acetylcholinesterase activity from being inhibited by two organophosphate simulants. We demonstrate that the utilized approach is an efficient and highly-extendable framework for the development of prophylactic therapeutics against organophosphate poisoning and other important targets. Our findings further suggest currently unknown molecular evolutionary rules governing natural diversity of the protein universe, which make it capable of recognizing previously unseen ligands. PMID:27845442

  1. EQCM Immunoassay for Phosphorylated Acetylcholinesterase as a Biomarker for Organophosphate Exposures Based on Selective Zirconia Adsorption and Enzyme-Catalytic Precipitation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Hua; Wang, Jun; Choi, Daiwon

    2009-03-01

    A zirconia (ZrO2) adsorption-based immunoassay by electrochemical quartz crystal microbalance (EQCM) has been initially developed, aiming at the detection of phosphorylated acetylcholinesterase (AChE) as a potential biomarker for bio-monitoring exposures to organophosphate (OP) pesticides and chemical warfare agents. Hydroxyl-derivatized monolayer was preferably chosen to modify the crystal serving as the template for directing the electro-deposition of ZrO2 film with uniform nanostructures. The resulting ZrO2 film was utilized to selectively capture phosphorylated AChE from the sample media. Horseradish peroxidase (HRP)-labeled anti-AChE antibodies were further employed to recognize the captured phosphorylated protein. Enzyme-catalytic oxidation of the benzidine substrate resulted in the accumulationmore » of insoluble product on the functionalized crystal. Ultrasensitive EQCM quantification by mass-amplified frequency responses as well as rapid qualification by visual color changes of product could be thus achieved. Moreover, 4-chloro-1-naphthol (CN) was comparably studied as an ideal chromogenic substrate for the enzyme-catalytic precipitation. Experimental results show that the developed EQCM technique can allow for the detection of phosphorylated AChE in human plasma. Such an EQCM immunosensing format opens a new door towards the development of simple, sensitive, and field-applicable biosensor for biologically monitoring low-level OP exposures.« less

  2. Urinary Metabolites of Organophosphate and Pyrethroid Pesticides and Behavioral Problems in Canadian Children

    PubMed Central

    Oulhote, Youssef

    2013-01-01

    Background: Exposure to organophosphate pesticides has been associated with neurobehavioral deficits in children, although data on low levels of exposure experienced by the general population are sparse. Pyrethroids are insecticides rapidly gaining popularity, and epidemiological evidence on their potential effects is lacking. Objective: We examined the association between exposure to organophosphate and pyrethroid pesticides, indicated by urinary metabolites, and parentally reported behavioral problems in children. Methods: We used data on children 6–11 years of age from the Canadian Health Measures Survey (2007–2009). We used logistic regressions to estimate odds ratios (ORs) for high scores on the Strengths and Difficulties Questionnaire (SDQ), which may indicate behavioral problems, in association with concentrations of pyrethroid and organophosphate metabolites in the urine of 779 children, adjusting for covariates (sex, age, race/ethnicity, income, parental education, blood lead levels, maternal smoking during pregnancy, and others). Results: At least one urinary metabolite for organophosphates was detected in 91% of children, and for pyrethroids in 97% of children. Organophosphate metabolites were not significantly associated with high SDQ scores. The pyrethroid metabolite cis-DCCA [3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropane carboxylic acid] was significantly associated with high scores for total difficulties on the SDQ (OR for a 10-fold increase = 2.0; 95% CI: 1.1, 3.6), and there was a nonsignificant association with trans-DCCA (OR = 1.6; 95% CI: 0.9, 3.0). Conclusion: In contrast with previous studies, we did not observe an association between exposure to organophosphate pesticides and behavioral scores in children. However, some pyrethroid urinary metabolites were associated with a high level of parent-reported behavioral problems. Longitudinal studies should be conducted on the potential risks of pyrethroids. Citation: Oulhote Y, Bouchard MF

  3. Neuropsychological Functioning in Gulf War Veterans Exposed to Pesticides and Pyridostigmine Bromide

    DTIC Science & Technology

    2008-08-01

    agents. Two subsets of these chemicals, organophosphates (OP) and carbamates , are known to produce chronic neurological symptoms with sufficient exposure ...e.g., organophosphates , carbamates ) on brain functioning and found different cognitive patterns with these exposures . For example, studies of...Krengel, Ph.D. & K. Sullivan, Ph.D. 52 more restricted organophosphate and carbamate pesticides products followed second in terms of increased exposures in

  4. Association between organophosphate pesticides exposure and thyroid hormones in floriculture workers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lacasana, Marina, E-mail: marina.lacasana.easp@juntadeandalucia.e; CIBER de Epidemiologia y Salud Publica; Lopez-Flores, Inmaculada

    The ability of organophosphate pesticides to disturb thyroid gland function has been demonstrated by experimental studies on animal, but evidence of such effects on human remains scarce. The aim of this study was to assess the association between exposure to organophosphate compounds and serum levels of thyroid hormones in floriculture workers. A longitudinal study was conducted on 136 male subjects from the State of Mexico and Morelos, Mexico, occupationally exposed to organophosphate pesticides, during agricultural periods of high (rainy season) and low (dry season) levels of pesticide application. Using a structured questionnaire, a survey was carried out on sociodemographic characteristics,more » anthropometry, clinical history, alcohol and tobacco consumption, residential chemical exposure, and occupational history. Urine and blood samples were taken the day after pesticide application to determine urine dialkylphosphate (DAP) levels, serum levels of TSH, total T{sub 3}, total T{sub 4}, serum PON1 activity, and serum p,p'-DEE levels. The analysis of the association between DAP levels and thyroid hormonal profile was carried out using multivariate generalized estimating equation (GEE) models. Our results showed an increase in both TSH and T{sub 4} hormones in serum associated with a increase in total dimethylphosphate levels (SIGMADMP) in urine (p-trend < 0.001) and a decrease in total T{sub 3} serum levels with an increase of SIGMADMP levels in the urine (p-trend = 0.053). These results suggest that exposure to organophosphate pesticides may be responsible of increasing TSH and T{sub 4} serum hormone levels and decreasing T{sub 3} serum hormone levels, therefore supporting the hypothesis that organophosphate pesticides act as endocrine disruptors in humans.« less

  5. Paraoxonase-1 genetic polymorphisms and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Singh, Satyender; Kumar, Vivek; Thakur, Sachin

    2011-04-15

    Human paraoxonase 1 (PON1) is a lipoprotein-associated enzyme involved in the detoxification of organophosphate pesticides (OPs) by hydrolyzing the bioactive oxons. Polymorphisms of the PON1 gene are responsible for variation in the expression and catalytic activity of PON1 enzyme. In the present study, we have determined (a) the prevalence of two common PON1 polymorphisms, (b) the activity of PON1 and acetylcholinesterase enzymes, and (c) the influence of PON1 genotypes and phenotypes variation on DNA damage in workers exposed to OPs. We examined 230 subjects including 115 workers exposed to OPs and an equal number of normal healthy controls. The resultsmore » revealed that PON1 activity toward paraoxon (179.19 {+-} 39.36 vs. 241.52 {+-} 42.32 nmol/min/ml in controls) and phenylacetate (112.74 {+-} 17.37 vs. 134.28 {+-} 25.49 {mu}mol/min/ml in controls) was significantly lower in workers than in control subjects (p < 0.001). No significant difference was observed in the distribution of genotypes and allelic frequencies of PON1{sub 192}QR (Gln/Arg) and PON1{sub 55}LM (Leu/Met) in workers and control subjects (p > 0.05). The PON1 activity toward paraoxonase was found to be significantly higher in the R/R (Arg/Arg) genotypes than Q/R (Gln/Arg) and lowest in Q/Q (Gln/Gln) genotypes in both workers and control subjects (p < 0.001). For PON1{sub 55}LM (Leu/Met), PON1 activity toward paraoxonase was observed to be higher in individuals with L/L (Leu/Leu) genotypes and lowest in individuals with M/M (Met/Met) genotypes in both groups (p < 0.001). No influence of PON1 genotypes and phenotypes was seen on the activity of acetylcholinesterase and arylesterase. The DNA damage was observed to be significantly higher in workers than in control subjects (p < 0.05). Further, the individuals who showed least paraoxonase activity i.e., those with (Q/Q [Gln/Gln] and M/M [Met/Met]) genotypes showed significantly higher DNA damage compared to other isoforms in workers exposed to OPs

  6. Development of a Computer-Based Survey Instrument for Organophosphate and N-Methyl-Carbamate Exposure Assessment among Agricultural Pesticide Handlers

    PubMed Central

    Hofmann, Jonathan N.; Checkoway, Harvey; Borges, Ofelio; Servin, Flor; Fenske, Richard A.; Keifer, Matthew C.

    2010-01-01

    Background: Assessment of occupational pesticide exposures based on self-reported information can be challenging, particularly with immigrant farm worker populations for whom specialized methods are needed to address language and cultural barriers and account for limited literacy. An audio computer-assisted self-interview (A-CASI) survey instrument was developed to collect information about organophosphate (OP) and N-methyl-carbamate (CB) exposures and other personal characteristics among male agricultural pesticide handlers for an ongoing cholinesterase biomonitoring study in Washington State. Objectives: To assess the feasibility of collecting data using the A-CASI instrument and evaluate reliability for a subset of survey items. Methods: The survey consisted of 64 items administered in Spanish or English on a touch-screen tablet computer. Participants listened to digitally recorded questions on headphones and selected responses on the screen, most of which were displayed as images or icons to facilitate participation of low literacy respondents. From 2006–2008, a total of 195 participants completed the survey during the OP/CB application seasons on at least one occasion. Percent agreement and kappa coefficients were calculated to evaluate test–retest reliability for selected characteristics among 45 participants who completed the survey on two separate occasions within the same year. Results: Almost all participants self-identified as Hispanic or Latino (98%), and 97% completed the survey in Spanish. Most participants completed the survey in a half-hour or less, with minimal assistance from on-site research staff. Analyses of test–retest reliability showed substantial agreement for most demographic, work history, and health characteristics and at least moderate agreement for most variables related to personal protective equipment use during pesticide applications. Conclusions: This A-CASI survey instrument is a novel method that has been used successfully

  7. BEHAVIORAL AND NEUROCHEMICAL CHANGES IN RATS DOSED REPEATEDLY WITH DIISOPROPYLFLUOROPHOSPHATE (DFP)

    EPA Science Inventory

    Behavioral effects of organophosphates (OPs) typically decrease with repeated exposure, despite persistence of OP-induced inhibition of acetylcholinesterase (AChE) and downregulation of muscarinic acetylcholine (ACh) receptors. o characterize this tolerance phenomenon, rats were ...

  8. Neurosteroids for the potential protection of humans against organophosphate toxicity.

    PubMed

    Reddy, Doodipala Samba

    2016-08-01

    This article describes the therapeutic potential of neurosteroids as anticonvulsant antidotes for chemical intoxication caused by organophosphate pesticides and nerve agents or gases like sarin and soman. Toxic manifestations following nerve agent exposure, as evident in chemical attacks in Japan and Syria, include hypersecretion, respiratory distress, tremors, convulsions leading to status epilepticus (SE), and death. Benzodiazepines, such as diazepam, are the current anticonvulsants of choice for controlling nerve agent-induced life-threatening seizures, SE, and brain injury. Benzodiazepines can control acute seizures when given early, but they are less effective for delayed treatment of SE, which is characterized by rapid desensitization of synaptic GABA A receptors, benzodiazepine resistance, and brain injury. Neurosteroid-sensitive extrasynaptic GABA A receptors, however, remain unaffected by such events. Thus, anticonvulsant neurosteroids may produce more effective protection than benzodiazepines against a broad spectrum of chemical agents, even when given late after nerve agent exposure. © 2016 New York Academy of Sciences.

  9. Associations of maternal organophosphate pesticide exposure and PON1 activity with birth outcomes in SAWASDEE birth cohort, Thailand

    PubMed Central

    Naksen, Warangkana; Prapamontol, Tippawan; Mangklabruks, Ampica; Chantara, Somporn; Thavornyutikarn, Prasak; Srinual, Niphan; Panuwet, Parinya; Ryan, P. Barry; Riederer, Anne M.; Barr, Dana Boyd

    2015-01-01

    Prenatal organophosphate (OP) pesticide exposure has been reported to be associated with adverse birth outcomes and neurodevelopment. However, the mechanisms of toxicity of OP pesticides on human fetal development have not yet been elucidated. Our pilot study birth cohort, the Study of Asian Women and Offspring’s Development and Environmental Exposures (SAWASDEE cohort) aimed to evaluate environmental chemical exposures and their relation to birth outcomes and infant neurodevelopment in 52 pregnant farmworkers in Fang district, Chiang Mai province, Thailand. A large array of data was collected multiple times during pregnancy including approximately monthly urine samples for evaluation of pesticide exposure, three blood samples for pesticide-related enzyme measurements and questionnaire data. This study investigated the changes in maternal acetylcholinesterase (AChE) and paraoxonase 1 (PON1) activities and their relation to urinary diakylphosphates (DAPs), class-related metabolites of OP pesticides, during pregnancy. Maternal AChE, butyrylcholinesterase (BChE) and PON1 activities were measured three times during pregnancy and urinary DAP concentrations were measured, on average, 8 times from enrollment during pregnancy until delivery. Among the individuals in the group with low maternal PON1 activity (n = 23), newborn head circumference was negatively correlated with log10 maternal ΣDEAP and ΣDAP at enrollment (gestational age=12±3 weeks; β = −1.0 cm, p = 0.03 and β = −1.8 cm, p <0.01, respectively) and at 32 weeks pregnancy (β = −1.1 cm, p = 0.04 and β = −2.6 cm, p = 0.01, respectively). Furthermore, among these mothers, newborn birthweight was also negatively associated with log10 maternal ΣDEAP and ΣDAP at enrollment (β = −219.7 g, p = 0.05 and β = −371.3 g, p = 0.02, respectively). Associations between maternal DAP levels and newborn outcomes were not observed in the group of participants with high maternal PON1 activity. Our results

  10. Microsomal biotransformation of chlorpyrifos, parathion and fenthion in rainbow trout (Oncorhynchus mykiss) and coho salmon (Oncorhynchus kisutch): mechanistic insights into interspecific differences in toxicity.

    PubMed

    Lavado, Ramon; Schlenk, Daniel

    2011-01-17

    Rainbow trout often serve as a surrogate species evaluating xenobiotic toxicity in cold-water species including other salmonids of the same genus, which are listed as threatened or endangered. Biotransformation tends to show species-specific patterns that influence susceptibility to xenobiotic toxicity, particularly organophosphate insecticides (OPs). To evaluate the contribution of biotransformation in the mechanism of toxicity of three organophosphate (phosphorothionate) insecticides, (chlorpyrifos, parathion and fenthion), microsomal bioactivation and detoxification pathways were measured in gills, liver and olfactory tissues in juvenile rainbow trout (Oncorhynchus mykiss) and compared to juvenile coho salmon (Oncorhynchus kisutch). Consistent with species differences in acute toxicity, significantly higher chlorpyrifos bioactivation was found in liver microsomes of rainbow trout (up to 2-fold) when compared with coho salmon. Although bioactivation to the oxon was observed, the catalytic efficiency towards chlorpyrifos dearylation (detoxification) was significantly higher in liver for both species (1.82 and 0.79 for trout and salmon, respectively) when compared to desulfuration (bioactivation). Bioactivation of parathion to paraoxon was significantly higher (up to 2.2-fold) than detoxification to p-nitrophenol in all tissues of both species with rates of conversion in rainbow trout, again significantly higher than coho salmon. Production of fenoxon and fenthion sulfoxides from fenthion was detected only in liver and gills of both species with activities in rainbow trout significantly higher than coho salmon. NADPH-dependent cleavage of fenthion was observed in all tissues, and was the only activity detected in olfactory tissues. These results indicate rainbow trout are more sensitive than coho salmon to the acute toxicity of OP pesticides because trout have higher catalytic rates of oxon formation. Thus, rainbow trout may serve as a conservative surrogate

  11. Assessing the connection between organophosphate pesticide poisoning and mental health: A comparison of neuropsychological symptoms from clinical observations, animal models and epidemiological studies.

    PubMed

    Stallones, Lorann; Beseler, Cheryl L

    2016-01-01

    Psychiatry and psychology are beginning to recognize the importance of lead, mercury and heavy metals as causal partners in the development of mental disorders. Further, mental health researchers and clinicians are embracing the idea that the combined effects of genetics and environmental exposures can result in perturbations in brain neurochemistry leading to psychiatric disorders. The purpose of this review is to examine the biological foundations for the epidemiological observations previously identified by reviewing the toxicology literature and relating it to epidemiological studies addressing the role of poisoning with organophosphate pesticides (OPs) in neurobehavioral and neuropsychological disorders. The goal of this review is to raise awareness in the mental health community about the possibility that affective disorders might be the result of contributions from environmental and occupational pesticide poisoning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. ORGANOPHOSPHORUS HYDROLASE-BASED ASSAY FOR ORGANOPHOSPHATE PESTICIDES

    EPA Science Inventory

    We report a rapid and versatile Organophosphorus hydrolase (OPH)-based method for measurement of organophosphates. This assay is based on a substrate-dependent change in pH at the local vicinity of the enzyme. The pH change is monitored using fluorescein isothiocyanate (FITC), ...

  13. Acute Pesticide Poisoning in Children: Hospital Review in Selected Hospitals of Tanzania.

    PubMed

    Lekei, Elikana; Ngowi, Aiwerasia V; London, Leslie

    2017-01-01

    Acute pesticide poisoning (APP) is a serious problem worldwide. Because the burden of childhood APP is unknown in Tanzania, this study describes the distribution, circumstances, and patterns of APP involving children under 18 years in Tanzania. A 12-month prospective study was conducted in 10 Tanzanian healthcare facilities in 2006 using a data collection tool for surveillance. Of 53 childhood poisoning cases identified, 56.6% were female. The most common poisoning circumstances were accidents (49.1%) and suicide (30.2%). The most vulnerable children were 16-17 years old (30.2%). Suicide was significantly more common in females (PRR females/males = 1.66; 95% CI = 1.03-2.68) and accidental cases were more common in children aged 10 years or younger. Suicide was concentrated in children over 10 years, comprising 53% of cases in this age group. Organophosphates (OPs), zinc phosphide, and endosulfan were common amongst reported poisoning agents. The annual APP incidence rate was 1.61/100,000. APP is common among children in this region of Tanzania. Prevention of suicide in older children should address mental health issues and control access to toxic pesticides. Prevention of accidents in younger children requires safer storage and hygiene measures. Diverse interventions are needed to reduce pesticide poisoning among children in Tanzania.

  14. Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: Tiapride vs. pyridostigmine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Petroianu, G.A.; Hasan, M.Y.; Nurulain, S.M.

    Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoximemore » reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 {mu}Mol paraoxon ({approx} LD{sub 75}) groups 2-6 received in addition: G{sub 2} 50 {mu}Mol tiapride 30 min before paraoxon; G{sub 3} 50 {mu}Mol tiapride 30 min before paraoxon and 50 {mu}Mol pralidoxime 1 min after paraoxon; G{sub 4} 1 {mu}Mol pyridostigmine 30 min before paraoxon; G{sub 5} 1 {mu}Mol pyridostigmine 30 min before paraoxon and 50 {mu}Mol pralidoxime 1 min after paraoxon; G{sub 6} 50 {mu}Mol pralidoxime 1 min after paraoxon; Mortality data were compared using Kaplan-Meier plots and logrank tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G{sub 3}) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G{sub 5}). Tiapride pretreatment only (G{sub 2}) is inferior to pyridostigmine pretreatment only (G{sub 4}). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G{sub 4} and G{sub 6})« less

  15. EEG SPECTRA, BEHAVIORAL STATES AND MOTOR ACTIVITY IN RATS EXPOSED TO ACETYLCHOLINESTERASE INHIBITOR CHLORPYRIFOS.

    EPA Science Inventory

    Exposure to organophosphate pesticides (OP) has been associated with sleep disorders: insomnia and ?excessive dreaming'. However neuronal mechanisms of these effects have not been analyzed. OP inhibit acetylcholinesterase activity leading to a hyperativity of the brain cholin...

  16. An unusual case of organophosphate intoxication of a worker in a plastic bottle recycling plant: an important reminder.

    PubMed Central

    Wang, C L; Chuang, H Y; Chang, C Y; Liu, S T; Wu, M T; Ho, C K

    2000-01-01

    A young man was sent to our emergency unit because he had suffered from vomiting and cold sweating for 2 days. At the time he was admitted, he had no acute abdominal pains or gastrointestinal symptoms, and a physical examination revealed nothing but a faster heart rate and moist, flushing skin. The patient had worked for 6 years at a plastic bottle-recycling factory, but none of his co-workers had the same symptoms. Nevertheless, because the plant also recycled pesticide bottles, we suspected organophosphate pesticide intoxication. The patient's plasma acetylcholinesterase level was checked, revealing 1498.6 microU/L (normal range: 2,000-5, 000) on the first day and 1,379 microU/L on the second day. Upon questioning, the patient recalled that one of his shoe soles had been damaged and that his foot had been wet from walking all day in rain collected on the factory floor on the day that his symptoms first occurred. We conducted a study in the change of preshift and postshift acetylcholinesterase levels among six of his co-workers on a rainy day. We used the Wilcoxon signed rank test to compare the preshift and postshift plasma acetylcholinesterase levels; no significant difference was revealed (p = 0.600), leaving contamination via the damaged shoe sole suspect. We reviewed the literature on organophosphate intoxication; pesticide bottle-recycling factories were reported to be at a low risk of organophosphate toxicity in the working environment. However, because the potential risk of intoxication is still present, protective equipment such as clothing, gloves, and water-proof shoes should be worn, and employees should be educated on the potential risks. PMID:11102304

  17. An unusual case of organophosphate intoxication of a worker in a plastic bottle recycling plant: an important reminder.

    PubMed

    Wang, C L; Chuang, H Y; Chang, C Y; Liu, S T; Wu, M T; Ho, C K

    2000-11-01

    A young man was sent to our emergency unit because he had suffered from vomiting and cold sweating for 2 days. At the time he was admitted, he had no acute abdominal pains or gastrointestinal symptoms, and a physical examination revealed nothing but a faster heart rate and moist, flushing skin. The patient had worked for 6 years at a plastic bottle-recycling factory, but none of his co-workers had the same symptoms. Nevertheless, because the plant also recycled pesticide bottles, we suspected organophosphate pesticide intoxication. The patient's plasma acetylcholinesterase level was checked, revealing 1498.6 microU/L (normal range: 2,000-5, 000) on the first day and 1,379 microU/L on the second day. Upon questioning, the patient recalled that one of his shoe soles had been damaged and that his foot had been wet from walking all day in rain collected on the factory floor on the day that his symptoms first occurred. We conducted a study in the change of preshift and postshift acetylcholinesterase levels among six of his co-workers on a rainy day. We used the Wilcoxon signed rank test to compare the preshift and postshift plasma acetylcholinesterase levels; no significant difference was revealed (p = 0.600), leaving contamination via the damaged shoe sole suspect. We reviewed the literature on organophosphate intoxication; pesticide bottle-recycling factories were reported to be at a low risk of organophosphate toxicity in the working environment. However, because the potential risk of intoxication is still present, protective equipment such as clothing, gloves, and water-proof shoes should be worn, and employees should be educated on the potential risks.

  18. Identification of Soil Properties and Organophosphate Residues From Agricultural Land in Wanasari Sub-District, Brebes, Indonesia

    NASA Astrophysics Data System (ADS)

    Joko, Tri; Anggoro, Sutrisno; Sunoko, Henna Rya; Rachmawati, Savitri

    2018-02-01

    Organophosphates have been used to eradicate pests and prevent losses from harvest failures caused by pest attack. It is undeniable that the organophosphate persist in soil. This study aims to identify the organophosphate residue and soil properties include pH, soil texture, and permeability. The soil samples were taken from cropland in 10 villages, Wanasari sub-district, Brebes, Indonesia. Organophosphate residue determined by gas chromatography using Flame Photometric Detector. Soil texture was determined by soil texture triangle from NRCS USDA, and the permeability value was determined by falling head method. The mean value of chlorpyrifos, profenofos, diazinon were 0.0078; 0.0388; 0.2271 mg/l respectively. The soil texture varies from clay, silt clay, loam, silt loam, and silt clay loam with permeability value at 10-7 with the soil pH value between 6.4 - 8.1. The results showed that organophosphate residues found in the soil and its potential affect the soil fertility decline. We recommend to conduct routine soil quality analysis to prevent soil damage in the agricultural environment.

  19. Is prevention of acute pesticide poisoning effective and efficient, with Locally Adapted Personal Protective Equipment? A randomized crossover study among farmers in Chitwan, Nepal.

    PubMed

    Varma, Anshu; Neupane, Dinesh; Ellekilde Bonde, Jens Peter; Jørs, Erik

    2016-07-26

    Farmers' risk of pesticide poisoning can be reduced with personal protective equipment but in low-income countries farmers' use of such equipment is limited. To examine the effectiveness and efficiency of Locally Adapted Personal Protective Equipment to reduce organophosphate exposure among farmers. In a crossover study, 45 male farmers from Chitwan, Nepal, were randomly allocated to work as usual applying organophosphate pesticides wearing Locally Adapted Personal Protective Equipment or Daily Practice Clothing. For seven days before each experiment, each farmer abstained from using pesticides. Before and after organophosphate application, an interview surveys and blood tests were carried out, and analyzed with paired t-test, frequencies and percentages. The difference between follow-up mean for acute organophosphate poisoning symptoms in the two groups was 0.13 [95% CI -0.22;0.49] and for plasma cholinesterase (U/ml) -0.03 [95% CI -0.11;0.06]. The difference between follow-up mean minus baseline mean for acute organophosphate poisoning symptoms in the two groups was 0.29 [95% CI -0.26;0.84] and for plasma cholinesterase (U/ml) -0.01 [95% CI --0.08;0.06]. Wearing the Locally Adapted Personal Protective Equipment versus Daily Practice Clothing gave the following results, respectively: comfort 75.6% versus 100%, sense of heat 64.4% versus 31.3%, other problems 44.4% versus 33.3%, likeability 95.6% versus 77.8%. We cannot support the expectation that our farmers in Chitwan, Nepal working with Locally Adapted Personal Protective Equipment would have fewer acute organophosphate poisoning symptoms, higher plasma cholinesterase (U/mL) and find it more efficient to work with the equipment than farmers working with their Daily Practice Clothing. Based on the farmers' working behavior, compounds used, intensity and exposure duration we conclude that Locally Adapted Personal Protective Equipment does not provide additional protection during usual work practices. However, our

  20. Neurobehavioral effects of exposure to organophosphates and pyrethroid pesticides among Thai children

    PubMed Central

    Fiedler, Nancy; Rohitrattana, Juthasiri; Siriwong, Wattasit; Suttiwan, Panrapee; Strickland, Pam Ohman; Ryan, P. Barry; Rohlman, Diane S.; Panuwet, Parinya; Barr, Dana Boyd; Robson, Mark G.

    2015-01-01

    The use of pesticides for crop production has grown rapidly in Thailand during the last decade, resulting in significantly greater potential for exposure among children living on farms. Although some previous studies assessed exposures to pesticides in this population, no studies have been conducted to evaluate corresponding health effects. Twenty-four children from a rice farming community (exposed) and 29 from an aquaculture (shrimp) community (control) completed the study. Participants completed a neurobehavioral test battery three times at 6 month intervals: Session I: preliminary orientation; Session II: high pesticide use season; Session III: low pesticide-use season. Only sessions II and III were used in the analyses. High and low pesticide use seasons were determined by pesticide use on rice farms. Urinary metabolites of organophosphates (OPs) and pyrethroids (PYR) were analyzed from first morning void samples collected the day of neurobehavioral testing. Rice farm participants had significantly higher concentrations of dialkylphosphates (DAPs) (common metabolites of OPs) and TCPy (a specific metabolite of chlorpyrifos) than aquaculture farm children regardless of season. But, TCPy was significantly higher during the low rather than the high pesticide use season for both participant groups. Rice farm children had significantly higher DCCA, a metabolite of PYR, than aquaculture participants only during the high exposure season. Otherwise, no significant differences in PYR metabolites were noted between the participant groups or seasons. No significant adverse neurobehavioral effects were observed between participant groups during either the high or low pesticide use season. After controlling for differences in age and the Home Observation for Measurement of the Environment (HOME) scores, DAPs, TCPy, and PYR were not significant predictors of adverse neurobehavioral performance during either season. Increasing DAP and PYR metabolites predicted some relatively

  1. Non-muscarinic therapeutic targets for acute organophosphorus poisoning.

    PubMed

    Rosenbaum, Christopher; Bird, Steven B

    2010-12-01

    Organophosphorus (OP) pesticides are a broad class of acetylcholinesterase inhibitors that are responsible for tremendous morbidity and mortality worldwide, contributing to an estimated 300,000 deaths annually. Current pharmacotherapy for acute OP poisoning includes the use of atropine, an oxime, and benzodiazepines. However, even with such therapy, the mortality from these agents is as high as 40%. It is increasingly recognized that not all OPs are the same. Significant differences exist in their toxicity, lipophilicity, and response to oxime therapy. Other non-muscarinic effects of OP pesticides exist, such as acute and chronic neuromuscular junction failure and central respiratory failure. In part because most of the mortality from these chemicals takes place in the developing world, little National Institutes of Health (NIH) research has been directed towards these agents. However, the similar mechanism of action of OP pesticides and the military nerve agents, along with increasing concerns about chemical terrorism has lead to the formation of the NIH Countermeasures Against Chemical Threats (CounterACT) Program. As part of the CounterACT Program, the NIH has recently designated six OP pesticides as "threat agents". This concept paper describes some of the knowledge gaps related to non-muscarinic effects of OP pesticides and highlights needed areas of further research. Leveraging the current NIH interest in these chemicals to medical necessities in the developing world offers the possibility of delivering new therapeutics where they are needed on a daily basis.

  2. Fluorescence spectroscopy approaches for the development of a real-time organophosphate detection system using an enzymatic sensor.

    PubMed

    Carullo, Paola; Cetrangolo, Giovanni Paolo; Mandrich, Luigi; Manco, Giuseppe; Febbraio, Ferdinando

    2015-02-09

    Organophosphates are organic substances that contain a phosphoryl or a thiophosphoryl bond. They are mainly used around the world as pesticides, but can also be used as chemical warfare agents. Their detection is normally entrusted to techniques like GC- and LC-MS that, although sensitive, do not allow their identification on site and in real time. We have approached their identification by exploiting the high-affinity binding of these compounds with the esterase 2 from Alicyclobacillus acidocaldarius. Using an in silico analysis to evaluate the binding affinities of the enzyme with organophosphate inhibitors, like paraoxon, and other organophosphate compounds, like parathion, chlorpyriphos, and other organophosphate thio-derivatives, we have designed fluorescence spectroscopy experiments to study the quenching of the tryptophan residues after esterase 2 binding with the organophosphate pesticides. The changes in the fluorescence signals permitted an immediate and quantitative identification of these compounds from nano- to picomolar concentrations. A fluorescence based polarity-sensitive probe (ANS) was also employed as a means to understand the extent of the interactions involved, as well as to explore other ways to detect organophosphate pesticides. Finally, we designed a framework for the development of a biosensor that exploits fluorescence technology in combination with a sensitive and very stable bio-receptor.

  3. Developmental Exposure to Organophosphate Flame Retardants Elicits Overt Toxicity and Alters Behavior in Zebrafish (Danio rerio)

    EPA Science Inventory

    Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect...

  4. Lanthanide Organophosphate Spiro Polymers: Synthesis, Structure, and Magnetocaloric Effect in the Gadolinium Polymer.

    PubMed

    Gupta, Sandeep K; Bhat, Gulzar A; Murugavel, Ramaswamy

    2017-08-07

    Spirocyclic lanthanide organophosphate polymers, {[Ln(dipp)(dippH)(CH 3 OH)(H 2 O) 2 ](CH 3 OH) 2 } n [Ln = La (1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6), Gd (7), Tb (8), Dy (9), Ho (10), Er (11)], have been prepared from the reaction of Ln(NO 3 ) 3 ·xH 2 O with sterically hindered 2,6-diisopropylphenyl phosphate (dippH 2 ) using aqueous NaOH as the base. The one-dimensional chainlike lanthanide (III) organophosphate coordination polymers have been characterized with the aid of analytical and spectroscopic methods. The single crystal structure determination of polymers (2-5 and 7-11) reveals that in these compounds the hydrophobic organic groups of the phosphate provide a protective coating for the inorganic lanthanide phosphate polymeric chain. The encapsulation of inorganic lanthanide phosphate core, which has very low solubility product, within the organic groups assists in the facile crystallization of the polymers. The di- and monoanionic organophosphate ligands dipp 2- and dippH - display [2.111] and [2.110] binding modes, respectively, in 2-5 and 7. However, they exhibit only [2.110] binding mode in the case of 8-11. This results in the formation of two different types of polymers. While the lighter rare-earth metal ions in 2-5 and 7 display eight coordinate biaugmented trigonal prismatic geometry, the heavier rare-earth metal ions in 9-11 exhibit a seven coordinate capped trigonal prismatic environment. The Tb(III) ion in 8 displays distorted pentagonal bipyramidal geometry. Magnetic studies reveal the presence of weak antiferromagnetic interactions between the Ln(III) ions through the organophosphate ligand. The isotropic Gd(III) polymer 7 exhibits a maximum entropy change of 17.83 J kg -1 K -1 for a field change of 7.0 T at 2.5 K, which is significant considering the high molecular weight of the organophosphate ligand. These polymers represent the first family of any structurally characterized rare-earth organophosphate polymers derived from monoesters

  5. Apoptosis of rat renal cells by organophosphate pesticide, quinalphos: Ultrastructural study.

    PubMed

    Eid, Refaat A

    2017-01-01

    Quinalphos or Ekalux, an organophosphate pesticide, is used in controlling the pests of a variety of crops. Quinalphos was studied on male Sprague-Dawley albino rats. The acute po LD50 of technical Ekalux was 19.95 mg/kg in males. Ekalux, produced several pathological changes in the kidney. A glomerulus demonstrated capillary lumina occluded by degenerated cellular debris. Basement membrane showed irregular wrinkling and branching. The proximal tubular cells showed damage such as dilation of endoplasmic reticulum, accumulation of glycogen granules, and pyknotic nucleus. The changes also included swelling of the mitochondria and reduction of the cristae up to total destruction. The distal tubular changes included electron lucency and vacuolation of cytoplasm. The distal convoluted tubule wall showed edematous epithelial cells, formation of blebs, and microvilli loss. These results suggest that subchronic exposure of rats to Ekalux causes ultrastructural changes in renal corpuscle and marked ultrastructural changes in proximal and distal tubules.

  6. Age-related differences in acute neurotoxicity produced by mevinphos, monocrotophos, dicrotophos, and phosphamidon

    EPA Science Inventory

    Age-related differences in the acute neurotoxicity of cholinesterase (ChE)-inhibiting pesticides have been well-studied for a few organophosphates, but not for many others. In this study, we directly compared dose-responses using brain and red blood cell (RBC) ChE measurements, a...

  7. Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents hypertrophy in single soleus fibers.

    PubMed

    Ohira, T; Wang, X D; Ito, T; Kawano, F; Goto, K; Izawa, T; Ohno, H; Kizaki, T; Ohira, Y

    2015-05-15

    Effects of macrophage on the responses of soleus fiber size to hind limb unloading and reloading were studied in osteopetrotic homozygous (op/op) mice with inactivated mutation of macrophage colony-stimulating factor (M-CSF) gene and in wild-type (+/+) and heterozygous (+/op) mice. The basal levels of mitotically active and quiescent satellite cell (-46 and -39% vs. +/+, and -40 and -30% vs. +/op) and myonuclear number (-29% vs. +/+ and -28% vs. +/op) in fibers of op/op mice were significantly less than controls. Fiber length and sarcomere number in op/op were also less than +/+ (-22%) and +/op (-21%) mice. Similar trend was noted in fiber cross-sectional area (CSA, -15% vs. +/+, P = 0.06, and -14% vs. +/op, P = 0.07). The sizes of myonuclear domain, cytoplasmic volume per myonucleus, were identical in all types of mice. The CSA, length, and the whole number of sarcomeres, myonuclei, and mitotically active and quiescent satellite cells, as well as myonuclear domain, in single muscle fibers were decreased after 10 days of unloading in all types of mice, although all of these parameters in +/+ and +/op mice were increased toward the control values after 10 days of reloading. However, none of these levels in op/op mice were recovered. Data suggest that M-CSF and/or macrophages are important to activate satellite cells, which cause increase of myonuclear number during fiber hypertrophy. However, it is unclear why their responses to general growth and reloading after unloading are different. Copyright © 2015 the American Physiological Society.

  8. Acetylcholinesterase of Rhipicephalus (Boophilus) microplus and Phlebotomus papatasi: Gene identification, expression, and biochemical properties of recombinant proteins

    USDA-ARS?s Scientific Manuscript database

    Rhipicephalus (Boophilus) microplus (Bm) ticks are vectors of bovine babesiosis and anaplasmosis. Tick resistance to organophosphate (OP) acaricide involves acetylcholinesterase (AChE) insensitivity to OP and metabolic detoxification. Sequencing and in vitro expression of Bm genes encoding AChE allo...

  9. Acetylcholinesterases of Rhipicephalus (Boophilus) microplus and Phlebotomus papatasi: Gene identification, expression and biochemical properties of recombinant proteins

    USDA-ARS?s Scientific Manuscript database

    Rhipicephalus (Boophilus) microplus (Bm) is a vector of bovine babesiosis and anaplasmosis. Tick resistance to organophosphate (OP) acaricide involves acetylcholinesterase (AChE) insensitivity to OP and metabolic detoxification. In vitro expression of Bm genes encoding AChE allowed biochemical chara...

  10. Complexity of acetylcholinesterases in biting flies and ticks

    USDA-ARS?s Scientific Manuscript database

    Acetylcholinesterase (AChE) inhibitors function as pesticides for invertebrates, vertebrate nerve agents, and medicine to reduce cognitive effects of Alzheimer’s disease. Organophosphate (OP) pesticides have been widely used to control biting flies and ticks, however, OP-resistance has compromised c...

  11. Surrealism Meets OP

    ERIC Educational Resources Information Center

    Bowden, Jennifer

    2006-01-01

    Kids always seem to like Surrealism and Op Art. This is a fun project that is popular with students. With Op Art patience and attention to details are required while Surrealistic collage needs strong composition skills for the image placement. Often, many images must be left out to create a clean design. Artistic decisions must be based on the art…

  12. THE OPS-1 MANUAL,

    DTIC Science & Technology

    wide range of human activity . Activities relating to management are the concern of a trial system at Project MAC called OPS-1. The OPS-1 system and the experiment that launched it are described in the manual. (Author)

  13. Candidate OP Phyla: Importance, Ecology and Cultivation Prospects.

    PubMed

    Rohini Kumar, M; Saravanan, V S

    2010-10-01

    OP phyla were created in the domain bacteria, based on the group of 16S rRNA gene sequences recovered from the Obsidian Pool. However, due to the lack of cultured representative it is referred to as candidate phyla. Wider ecological occurrence was predicted for the OP phyla, especially OP3, OP10 and OP11. Recently, members of phylum OP5 and OP10 were cultured, providing clues to their cultivation prospects. At last the bioprospecting potentials of the OP members are discussed herein.

  14. Urinary Pyrethroid and Chlorpyrifos Metabolite Concentraitons in Northern California families and their relationship to indoor home insecticide levels, part of the Study of Use of Products and Exposure Related Behavior (SUPERB)

    EPA Science Inventory

    Since the 2001 U.S. federally mandated phase-out of residential uses of organophosphate (OP) insecticides, the use of and potential for human exposure to pyrethroid insecticides in the indoor residential environment increases, while that for OPs decreases. Here we report indoor ...

  15. Bioscavengers for the protection of humans against organophosphate toxicity.

    PubMed

    Doctor, Bhupendra P; Saxena, Ashima

    2005-12-15

    Current antidotes for organophosphorus compounds (OP) poisoning consist of a combination of pretreatment with carbamates (pyridostigmine bromide), to protect acetylcholinesterase (AChE) from irreversible inhibition by OP compounds, and post-exposure therapy with anti-cholinergic drugs (atropine sulfate) to counteract the effects of excess acetylcholine and oximes (e.g., 2-PAM chloride) to reactivate OP-inhibited AChE. These antidotes are effective in preventing lethality from OP poisoning, but they do not prevent post-exposure incapacitation, convulsions, seizures, performance decrements, or in many cases permanent brain damage. These symptoms are commonly observed in experimental animals and are likely to occur in humans. The problems intrinsic to these antidotes stimulated attempts to develop a single protective drug, itself devoid of pharmacological effects, which would provide protection against the lethality of OP compounds and prevent post-exposure incapacitation. One approach is the use of enzymes such as cholinesterases (ChEs), beta-esterases in general, as single pretreatment drugs to sequester highly toxic OP anti-ChEs before they reach their physiological targets. This approach turns the irreversible nature of the OP: ChE interaction from disadvantage to an advantage; instead of focusing on OP as an anti-ChE, one can use ChE as an anti-OP. Using this approach, it was shown that administration of fetal bovine serum AChE (FBSAChE) or equine serum butyrylcholinesterase (EqBChE) or human serum BChE (HuBChE) protected the animals from multiple LD50s of a variety of highly toxic OPs without any toxic effects or performance decrements. The bioscavengers that have been explored to date for the detoxification of OPs fall into three categories: (A) those that can catalytically hydrolyze OPs and thus render them non-toxic, such as OP hydrolase and OP anhydrase; (B) those that stoichiometrically bind to OPs, that is, 1 mol of enzyme neutralizes one or 2 mol of OP

  16. Gas-Phase Stability of Negatively Charged Organophosphate Metabolites Produced by Electrospray Ionization and Matrix-Assisted Laser Desorption/Ionization

    NASA Astrophysics Data System (ADS)

    Asakawa, Daiki; Mizuno, Hajime; Toyo'oka, Toshimasa

    2017-12-01

    The formation mechanisms of singly and multiply charged organophosphate metabolites by electrospray ionization (ESI) and their gas phase stabilities were investigated. Metabolites containing multiple phosphate groups, such as adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP), and D- myo-inositol-1,4,5-triphosphate (IP3) were observed as doubly deprotonated ions by negative-ion ESI mass spectrometry. Organophosphates with multiple negative charges were found to be unstable and often underwent loss of PO3 -, although singly deprotonated analytes were stable. The presence of fragments due to the loss of PO3 - in the negative-ion ESI mass spectra could result in the misinterpretation of analytical results. In contrast to ESI, matrix-assisted laser desorption ionization (MALDI) produced singly charged organophosphate metabolites with no associated fragmentation, since the singly charged anions are stable. The stability of an organophosphate metabolite in the gas phase strongly depends on its charge state. The fragmentations of multiply charged organophosphates were also investigated in detail through density functional theory calculations. [Figure not available: see fulltext.

  17. Effects of Organophosphate Esters on Neuropeptide Systems.

    DTIC Science & Technology

    1986-03-01

    pathways for the synthesis and degradation of neuropeptides involve hydrolytic enzyme reactions which may be mechanistically similar to those catalyzed by...neuropeptide processing and degradation in vitro, and to assess the effect of introducing organophosphates into these systems. The methods used for the...weight precursors by proteolytic cleavage and inactivation, in which the mature neuropeptides are hydrolyzed by peptidases . More importantly

  18. Acute Pesticide Poisoning in Children: Hospital Review in Selected Hospitals of Tanzania

    PubMed Central

    London, Leslie

    2017-01-01

    Background Acute pesticide poisoning (APP) is a serious problem worldwide. Because the burden of childhood APP is unknown in Tanzania, this study describes the distribution, circumstances, and patterns of APP involving children under 18 years in Tanzania. Methodology A 12-month prospective study was conducted in 10 Tanzanian healthcare facilities in 2006 using a data collection tool for surveillance. Results Of 53 childhood poisoning cases identified, 56.6% were female. The most common poisoning circumstances were accidents (49.1%) and suicide (30.2%). The most vulnerable children were 16-17 years old (30.2%). Suicide was significantly more common in females (PRR females/males = 1.66; 95% CI = 1.03–2.68) and accidental cases were more common in children aged 10 years or younger. Suicide was concentrated in children over 10 years, comprising 53% of cases in this age group. Organophosphates (OPs), zinc phosphide, and endosulfan were common amongst reported poisoning agents. The annual APP incidence rate was 1.61/100,000. Conclusion APP is common among children in this region of Tanzania. Prevention of suicide in older children should address mental health issues and control access to toxic pesticides. Prevention of accidents in younger children requires safer storage and hygiene measures. Diverse interventions are needed to reduce pesticide poisoning among children in Tanzania. PMID:29441090

  19. Interaction between organophosphate pesticide exposure and PON1 activity on thyroid function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lacasana, Marina, E-mail: marina.lacasana.easp@juntadeandalucia.e; CIBER de Epidemiologia y Salud Publica; Lopez-Flores, Inmaculada

    Organophosphate pesticides are widely used in agricultural purposes. Recently, a few studies have demonstrated the ability of these chemicals to alter the function of the thyroid gland in human. Moreover, the paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity. This study evaluates the interaction between exposure to organophosphate compounds and PON1 enzyme activity on serum levels of TSH and thyroid hormones in a population of workers occupationally exposed to pesticides. A longitudinal study was conducted on a population of floriculture workers from Mexico, duringmore » two periods of high and low-intensity levels of pesticide application. A structured questionnaire was completed by workers containing questions on sociodemographic characteristics and other variables of interest. Urine and blood samples were taken, and biomarkers of exposure (dialkylphosphates), susceptibility (PON1 polymorphisms and activity) and effect (thyroid hormone levels) were determined. Interaction between dialkylphosphates and PON1 polymorphisms or PON1 activity on hormone levels was evaluated by generalized estimating equation (GEE) models. A significant interaction was found between serum diazoxonase activity and total dialkylphosphates ({Sigma}DAP) on TSH levels. Thus, when PON1 activity was increased we observed a decrease in the percentage of variation of TSH level for each increment in one logarithmic unit of the {Sigma}DAP levels. This interaction was also observed with the PON1{sub 192}RR genotype. These results suggest a stronger association between organophosphate pesticides and thyroid function in individuals with lower PON1 activity.« less

  20. Effect of stress at dosing on organophosphate and heavy metal toxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jortner, Bernard S.

    2008-11-15

    This paper reviews recent studies assessing the effect of well-defined, severe, transient stress at dosing on two classical models of toxicity. These are the acute (anticholinesterase) toxicity seen following exposure to the organophosphate insecticide chlorpyrifos, and the nephrotoxicity elicited by the heavy metal depleted uranium, in rats. Stress was induced by periods of restraint and forced swimming in days to weeks preceding toxicant exposure. Forced swimming was far more stressful, as measured by marked, if transient, elevation of plasma corticosterone. This form of stress was administered immediately prior to administration of chlorpyrifos or depleted uranium. Chlorpyrifos (single 60 mg/kg subcutaneously)more » elicited marked inhibition of brain acetylcholinesterase 4-day post-dosing. Depleted uranium (single intramuscular doses of 0.1, 0.3 or 1.0 mg/kg uranium) elicited dose-dependent increase in kidney concentration of the metal, with associated injury to proximal tubular epithelium and increases in serum blood urea nitrogen and creatinine during the 30-day post-dosing period. Stress at dosing had no effect on these toxicologic endpoints.« less

  1. Seasonal and occupational trends of five organophosphate pesticides in house dust.

    PubMed

    Smith, Marissa N; Workman, Tomomi; McDonald, Katie M; Vredevoogd, Melinda A; Vigoren, Eric M; Griffith, William C; Thompson, Beti; Coronado, Gloria D; Barr, Dana; Faustman, Elaine M

    2017-07-01

    Since 1998, the University of Washington's Center for Child Environmental Health Risks Research has followed a community-based participatory research strategy in the Lower Yakima Valley of Washington State to assess pesticide exposure among families of Hispanic farmworkers. As a part of this longitudinal study, house dust samples were collected from both farmworker and non-farmworker households, across three agricultural seasons (thinning, harvest and non-spray). The household dust samples were analyzed for five organophosphate pesticides: azinphos-methyl, phosmet, malathion, diazinon, and chlorpyrifos. Organophosphate pesticide levels in house dust were generally reflective of annual use rates and varied by occupational status and agricultural season. Overall, organophosphate pesticide concentrations were higher in the thinning and harvest seasons than in the non-spray season. Azinphos-methyl was found in the highest concentrations across all seasons and occupations. Farmworker house dust had between 5- and 9-fold higher concentrations of azinphos-methyl than non-farmworker house dust. Phosmet was found in 5-7-fold higher concentrations in farmworker house dust relative to non-farmworker house dust. Malathion and chlorpyriphos concentrations in farmworker house dust ranged between 1.8- and 9.8-fold higher than non-farmworker house dust. Diazinon showed a defined seasonal pattern that peaked in the harvest season and did not significantly differ between farmworker and non-farmworker house dust. The observed occupational differences in four out of five of the pesticide residues measured provides evidence supporting an occupational take home pathway, in which workers may bring pesticides home on their skin or clothing. Further, these results demonstrate the ability of dust samples to inform the episodic nature of organophosphate pesticide exposures and the need to collect multiple samples for complete characterization of exposure potential.

  2. Pattern of acute food, drug, and chemical poisoning in Sari City, Northern Iran.

    PubMed

    Ahmadi, Amirhossein; Pakravan, Nasrin; Ghazizadeh, Zeynab

    2010-09-01

    This descriptive and retrospective study was conducted at the poisoning ward of Imam teaching hospital, Sari, Iran, with the aim of evaluating the pattern of poisoning. Hence, the medical profiles of 2057 patients, who were admitted, were carefully reviewed during the period from April 2006 to March 2008 for 2 years. During this period, 2057 cases, 53.9% female and 46.1% male, were admitted with the indication of acute poisoning. The greatest proportion of poisoning occurred between the ages of 18 and 29 years, with suicidal intentions. Most cases of poisoning were intentional (85%). The most common agents involved in acute poisoning were drugs (77.7%), especially sedatives/hypnotics such as benzodiazepines, followed by opioid analgesics. Organophosphate and carbamate insecticides were the third major agent that induced poisoning. Twenty-seven patients (1.3%) who were mostly females and young adults died. Death mostly occurred due to organophosphate and carbamate insecticides (19 cases) poisoning, followed by sedatives/hypnotics like benzodiazepines (3 cases). High prevalence of intentional overdose and mortality among young adults requires considerable attention and further studies to find out the underlying causes. In addition, strict rules must be followed regarding the sale of central nervous system drugs and pesticides, particularly organophosphate and carbamate insecticides. Establishing poison information centers in different parts of the country, preparing national treatment guidelines, training healthcare providers, and ensuring easy availability of the antidotes are also recommended.

  3. Protective effect of metoclopramide against organophosphate-induced apoptosis in the murine skin fibroblast L929.

    PubMed

    Jaber, Basem M; Petroianu, Georg A; Rizvi, Syed A; Borai, Anwar; Saleh, Nada A; Hala, Sharif M; Saleh, Ayman M

    2018-03-01

    This study was performed to evaluate the protective efficacy of metoclopramide (MCP) against the organophosphates paraoxon (POX)- and malathion (MLT)-induced apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either POX (10 nm) or 1.0 μm MLT in the absence and presence of increased concentrations of MCP. The protective effect of MCP on these organophosphate-stimulated apoptotic events was evaluated by flow cytometry analysis after staining with annexin-V/propidium iodide, processing and activation of the executioner caspase-3, cleavage of the poly-ADP ribose polymerase, fragmentation of the nucleosomal DNA and disruption of the mitochondrial membrane potential (Δψ). Our results showed that increased doses of MCP alone (≥10 μm) did not induce apoptosis or activation of caspase-3. Pretreatment of the cells with MCP attenuated all the apoptotic events triggered by the organophosphate compounds in a dose-dependent manner reaching ~70-80% protection when they were preincubated at 1 and 5 μm of the drug before the addition of POX and MLT, respectively. Interestingly, MCP did not offer a significant protective effect against the cytotoxicity of tumor necrosis factor-α, cisplatinum, etoposide or paclitaxel, which stimulate apoptosis by various mechanisms, suggesting that the anti-apoptotic effect of the drug is specific to organophosphates. The strong and specific anti-apoptotic activity of subclinical doses of MCP against the cytotoxicity of organophosphate compounds suggests its potential clinical application in treating their poisoning. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Paraoxon and Pyridostigmine Interfere with Neural Stem Cell Differentiation

    PubMed Central

    Berríos, Verónica O.; Boukli, Nawal M.; Rodriguez, Jose W.; Negraes, Priscilla D.; Schwindt, Telma T.; Trujillo, Cleber A.; Oliveira, Sophia L. B.; Cubano, Luis A.; Ferchmin, P. A.; Eterovic, Vesna A.; Ulrich, Henning; Martins, Antonio H.

    2015-01-01

    Acetylcholinesterase (AChE) inhibition has been described as the main mechanism of organophosphate (OP)-evoked toxicity. OPs represent a human health threat, because chronic exposure to low doses can damage the developing brain, and acute exposure can produce long-lasting damage to adult brains, despite post-exposure medical countermeasures. Although the main mechanism of OP toxicity is AChE inhibition, several lines of evidence suggest that OPs also act by other mechanisms. We hypothesized that rat neural progenitor cells extracted on embryonic day 14.5 would be affected by constant inhibition of AChE from chronic exposure to OP or pyri-dostigmine (a reversible AChE blocker) during differentiation. In this work, the OP paraoxon decreased cell viability in concentrations >50 μM, as measured with the MTT assay; however, this effect was not dose-dependent. Reduced viability could not be attributed to blockade of AChE activity, since treatment with 200 μM pyri-dostigmine did not affect cell viability, even after 6 days. Although changes in protein expression patterns were noted in both treatments, the distribution of differentiated phenotypes, such as the percentages of neurons and glial cells, was not altered, as determined by flow cytometry. Since paraoxon and pyridostigmine each decreased neurite outgrowth (but did not prevent differentiation), we infer that developmental patterns may have been affected. PMID:25758980

  5. Paraoxon and Pyridostigmine Interfere with Neural Stem Cell Differentiation.

    PubMed

    Berríos, Verónica O; Boukli, Nawal M; Rodriguez, Jose W; Negraes, Priscilla D; Schwindt, Telma T; Trujillo, Cleber A; Oliveira, Sophia L B; Cubano, Luis A; Ferchmin, P A; Eterović, Vesna A; Ulrich, Henning; Martins, Antonio H

    2015-10-01

    Acetylcholinesterase (AChE) inhibition has been described as the main mechanism of organophosphate (OP)-evoked toxicity. OPs represent a human health threat, because chronic exposure to low doses can damage the developing brain, and acute exposure can produce long-lasting damage to adult brains, despite post-exposure medical countermeasures. Although the main mechanism of OP toxicity is AChE inhibition, several lines of evidence suggest that OPs also act by other mechanisms. We hypothesized that rat neural progenitor cells extracted on embryonic day 14.5 would be affected by constant inhibition of AChE from chronic exposure to OP or pyridostigmine (a reversible AChE blocker) during differentiation. In this work, the OP paraoxon decreased cell viability in concentrations >50 μM, as measured with the MTT assay; however, this effect was not dose-dependent. Reduced viability could not be attributed to blockade of AChE activity, since treatment with 200 µM pyridostigmine did not affect cell viability, even after 6 days. Although changes in protein expression patterns were noted in both treatments, the distribution of differentiated phenotypes, such as the percentages of neurons and glial cells, was not altered, as determined by flow cytometry. Since paraoxon and pyridostigmine each decreased neurite outgrowth (but did not prevent differentiation), we infer that developmental patterns may have been affected.

  6. SIGNALING PATHWAYS ASSOCIATED WITH VX EXPOSURE IN MESENCHYMAL STEM CELLS

    DTIC Science & Technology

    2017-09-01

    organophosphate (OP) pesticides sustain significant changes in their ability to proliferate and differentiate. In the literature, OP compounds were shown...3 2.1 Human MSC Culture .........................................................................................3...Biological Center (ECBC) BioDefense Branch team members demonstrated that bone marrow-derived human mesenchymal stem cells (MSCs) that are exposed

  7. A case report of motor neuron disease in a patient showing significant level of DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane and toluene in blood

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kanavouras, Konstantinos; Tzatzarakis, Manolis N.; Mastorodemos, Vasileios

    Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology. Several epidemiological studies have suggested that occupational exposure to chemicals may be associated with disease pathogenesis. We report the case of a patient developing progressive motor neuron disease, who was chronically exposed to pesticides and organic solvents. The patient presented with leg spasticity and developed gradually clinical signs suggestive of amyotrophic lateral sclerosis, which was supported by the neurophysiologic and radiological findings. Our report is an evidence based case of combined exposure to organochlorine (DDTs), organophosphate pesticides (OPs) and organic solventsmore » as confirmed by laboratory analysis in samples of blood and hair confirming systematic exposure. The concentration of non-specific dialkylphosphates metabolites (DAPs) of OPs in hair (dimethyphopshate (DMP) 1289.4 pg/mg and diethylphosphate (DEP) 709.4 pg/mg) and of DDTs (opDDE 484.0 pg/mg, ppDDE 526.6 pg/mg, opDDD 448.4 pg/mg, ppDDD + opDDT 259.9 pg/mg and ppDDT 573.7 pg/mg) were considerably significant. Toluene and n-hexane were also detected in blood on admission at hospital and quantified (1.23 and 0.87 {mu}g/l, respectively), while 3 months after hospitalization blood testing was found negative for toluene and n-hexane and hair analysis was provided decrease levels of HCHs, DDTs and DAPs. -- Highlights: Black-Right-Pointing-Pointer Exposure to pesticides and organic solvents might be a risk factor for sporadic MND. Black-Right-Pointing-Pointer We report a patient who developed progressive upper and lower motor neuron disease. Black-Right-Pointing-Pointer The patient had a history of occupational exposure to pesticides and solvents. Black-Right-Pointing-Pointer High DDTs' levels and increased levels of DMP and DEP were measured in his hair. Black-Right-Pointing-Pointer The patients' exposure to chemicals might have

  8. Oximes in organophosphate poisoning: 60 years of hope and despair.

    PubMed

    Worek, Franz; Thiermann, Horst; Wille, Timo

    2016-11-25

    The high number of annual fatalities following suicidal poisoning by organophosphorus (OP) pesticides and the recent homicidal use of the chemical warfare nerve agent sarin against civilian population in Syria underlines the continuous threat by these highly toxic agents. The need for an effective treatment of OP poisoning resulted in the implementation of a combination therapy with the muscarinic receptor antagonist atropine and an oxime for the reactivation of OP-inhibited acetylcholinesterase (AChE). Since the invention of the first clinically used oxime pralidoxime (2-PAM) in the 1950s ongoing research attempted to identify more effective oximes. In fact, several thousand oximes were synthesized in the past six decades. These include charged and non-charged compounds, mono- and bispyridinium oximes, asymmetric oximes, oximes with different substitutes and more recently non-oxime reactivators. Multiple in vitro and in vivo studies investigated the potential of oximes to reactivate OP-inhibited AChE and to reverse OP-induced cholinergic signs. Depending on the experimental model, the investigated species and the tested OP largely variable results were obtained by different laboratories. These findings and the inconsistent effectiveness of oximes in the treatment of OP-pesticide poisoned patients led to a continuous discussion on the value of oximes. In order to provide a forward-looking evaluation of the significance of oximes in OP poisoning multiple aspects, including intrinsic toxicity, in vitro reactivation potency, efficacy and pharmacokinetics, as well as the impact of the causative OP have to be considered. The different influencing factors in order to define the benefit and limitations of oximes in OP poisoning will be discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Central nervous system effect of chronic exposure to organophosphate insecticides.

    DOT National Transportation Integrated Search

    1963-10-01

    Two cases are reported in which persistent CNS changes were noted in aerial applicator pilots after chronic exposure to organophosphate insecticides. The synptomatology, the basis for these symptoms and EEG changes and their reversibility are discuss...

  10. Prevalence of tinnitus in workers exposed to noise and organophosphates

    PubMed Central

    Delecrode, Camila Ribas; de Freitas, Thais Domingues; Frizzo, Ana Claúdia Figueiredo; Cardoso, Ana Claúdia Vieira

    2012-01-01

    Summary Introduction: Research on the workplace has emphasized the effects of noise exposure on workers' hearing, but has not considered the effects of agrochemicals. Aim: To evaluate and correlate the hearing level and tinnitus of workers exposed simultaneously to noise and organophosphates in their workplace and to measure tinnitus distress on their quality of life. Method: A retrospective clinical study. We evaluated 82 organophosphate sprinklers from the São Paulo State Regional Superintendence who were active in the fight against dengue and who were exposed to noise and organophosphates. We performed pure tone audiometry and applied the translated THI (Tinnitus Handicap Inventory) questionnaire. Results: Of the sample, 28.05% reported current tinnitus or had presented tinnitus, and the workers with tinnitus had an increased incidence of abnormal audiometry. The average hearing threshold for the 4–8-kHz frequency range of the workers with current tinnitus was higher than that of the others, and was most affected at the 4-kHz frequency. The THI score ranged 0–84, with an average score of 13.1. Twelve (52.17%) workers had THI scores consistent with discrete handicap. Conclusion: There is an increased incidence of abnormal pure tone audiometry in workers with tinnitus, and its impact on the workers' quality of life was discrete. The correlation between average hearing threshold and tinnitus distress was weak. PMID:25991953

  11. Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcome drug resistance in myeloid leukemia

    PubMed Central

    Agarwal, Anupriya; MacKenzie, Ryan J.; Pippa, Raffaella; Eide, Christopher A.; Oddo, Jessica; Tyner, Jeffrey W.; Sears, Rosalie; Vitek, Michael P.; Odero, María D.; Christensen, Dale; Druker, Brian J.

    2014-01-01

    Purpose The SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A), is overexpressed in leukemia. We evaluated the efficacy of SET antagonism in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) cell lines, a murine leukemia model, and primary patient samples using OP449, a specific, cell-penetrating peptide that antagonizes SET's inhibition of PP2A. Experimental Design In vitro cytotoxicity and specificity of OP449 in CML and AML cell lines and primary samples were measured using proliferation, apoptosis and colonogenic assays. Efficacy of target inhibition by OP449 is evaluated by immunoblotting and PP2A assay. In vivo antitumor efficacy of OP449 was measured in human HL-60 xenografted murine model. Results We observed that OP449 inhibited growth of CML cells including those from patients with blastic phase disease and patients harboring highly drug-resistant BCR-ABL1 mutations. Combined treatment with OP449 and ABL1 tyrosine kinase inhibitors was significantly more cytotoxic to K562 cells and primary CD34+ CML cells. SET protein levels remained unchanged with OP449 treatment, but BCR-ABL1-mediated downstream signaling was significantly inhibited with the degradation of key signaling molecules such as BCR-ABL1, STAT5, and AKT. Similarly, AML cell lines and primary patient samples with various genetic lesions showed inhibition of cell growth after treatment with OP449 alone or in combination with respective kinase inhibitors. Finally, OP449 reduced the tumor burden of mice xenografted with human leukemia cells. Conclusions We demonstrate a novel therapeutic paradigm of SET antagonism using OP449 in combination with tyrosine kinase inhibitors for the treatment of CML and AML. PMID:24436473

  12. One Stop Post Op cardiac surgery recovery--a proven success.

    PubMed

    Joyce, L; Pandolph, P

    2001-01-01

    The One Stop Post Op model for open heart surgery recovery is an innovative approach to post op care utilized in only a few facilities in the country. This model calls for an integration of acute ICU and step-down phases of care, thus changing the paradigm for nursing care of the open heart surgery patient. Typically, hospitals incur inefficiencies transferring the patient through multiple levels of care, thus resulting in a "disconnect" as new caregivers relearn the patient's care requirements and special needs. The construction of a "one stop" unit allows the patient to remain stationary while the service level changes to accommodate changing care needs. The cardiac "one stop" model is similar to the LDRP concept for obstetrical care. The One Stop Post Op patient rooms are designed to accommodate every level of patient acuity. All rooms meet the regulations for critical care room design, however this is where the aesthetic similarity ends. The patient environment looks more like hotel rooms rather than the traditional ICU setting. Cabinets designed to cover medical gases, in the room's private bathrooms and comfortable furnishings help to create a patient focused environment conducive to recovery. This model has been utilized by several facilities and has demonstrated clear clinical and economic advantages for patients, families, and health care providers. Implementing an open heart surgery (OHS) program presents the opportunity for several community based hospitals to challenge the way they have been providing patient care and establish an innovative approach to post surgery patient care. The One Stop Post Op cardiovascular recovery unit is designed to receive the OHS patient directly from the operating room and to be the "care unit" for the patient's entire stay. Patient flow, quality monitoring and caregiver acceptance in this unit requires new paradigms from the traditional two or three step post OHS care delivery process. The One Stop Post Op model focuses

  13. Wearable Flexible and Stretchable Glove Biosensor for On-Site Detection of Organophosphorus Chemical Threats

    DTIC Science & Technology

    2017-03-03

    finger enables rapid on-site detection of organophosphate (OP) nerve-agent compounds on suspicious surfaces and agricultural products following their...used as pesticides in agricultural and domestic settings.21,22 These OP neurotoxins severely affect the nervous system and lead to rapid death. Due to...The “on-hand” detection of different OP chemical agents on a variety of surfaces and agricultural foodstuffs demonstrate that the new wireless glove

  14. Changing trends and predictors of outcome in patients with acute poisoning admitted to the intensive care.

    PubMed

    Jayashree, M; Singhi, S

    2011-10-01

    Acute poisoning in children is a medical emergency and preventable cause of morbidity and mortality. Knowledge about the nature, magnitude, outcome and predictors of outcome is necessary for management and allocation of scant resources. This is a retrospective study conducted in the Pediatric Intensive Care Unit (PICU) of an urban multi speciality teaching and referral hospital in North India from January 1993 to June 2008 to determine the epidemiology, clinical profile, outcome and predictors of outcome in children with acute poisoning. Data of 225 children with acute poisoning was retrieved from case records with respect to demographic profile, time to presentation, PRISM score, clinical features, investigations, therapeutic measures, complications and outcome in terms of survival or death. Survivors and non-survivors were compared to determine the predictors of mortality. Acute poisoning constituted 3.9% of total PICU admissions; almost all (96.9%) were accidental. The mean age of study patient's was 3.3 ± 3.1 (range 0.10-12) years with majority (61.3%) being toddlers (1-3 years). In the overall cohort, kerosene (27.1%) and prescription drugs (26.7%) were the most common causative agents followed by organophosphates (16.0%), corrosives (7.6%), carbamates (4.9%) and aluminum phosphide (4.9%). However the trends of the three 5-year interval (1993 till the end of 1997, 1998 till the end of 2002 and 2003 till the end of June 2008) revealed a significant decrease in kerosene, aluminum phosphide and iron with increase in organophosphate compound poisoning. Ninety nine (44%) patients required supplemental oxygen, of which nearly half (n = 42; 42.4%) needed mechanical ventilation. Twenty (8.9%) died; cause of death being iron poisoning in five; aluminum phosphide in four; organophosphates in three and one each because of kerosene, diesel, carbamate, corrosive, sewing machine lubricant, isoniazid, salicylate and maduramycin poisoning. There has been a significant

  15. The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children.

    PubMed

    Chang, Chia-Huang; Yu, Ching-Jung; Du, Jung-Chieh; Chiou, Hsien-Chih; Chen, Hsin-Chang; Yang, Winnie; Chung, Ming-Yi; Chen, Ying-Sheue; Hwang, Betau; Mao, I-Fang; Chen, Mei-Lien

    2018-01-01

    The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified. Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95µg/g cre. vs. 16.55µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24-0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13-1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12-65.04). This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Repeated exposures to diisopropylfluorophosphate result in impairments of sustained attention and persistent alterations of inhibitory response control in rats

    PubMed Central

    Terry, Alvin V.; Callahan, Patrick M.; Beck, Wayne D.; Vandenhuerk, Leah; Sinha, Samantha; Bouchard, Kristy; Schade, Rose; Waller, Jennifer L.

    2014-01-01

    Organophosphate (OP)-based chemicals are used worldwide for many purposes and they have likely saved millions of people from starvation and disease. However, due to their toxicity they can also pose a significant environmental risk. While considerable research has focused on the acute symptoms and long-term consequences of overtly toxic exposures to OPs, less attention has been given to the subject of repeated exposures to levels that are not associated with acute symptoms (subthreshold exposures). There is clinical evidence indicating that this type of OP exposure can lead to prolonged deficits in cognition; however only a few studies have addressed this issue prospectively in animal models. In this study, repeated subthreshold exposures to the OP nerve agent diisopropylfluorophosphate (DFP) were evaluated in a 5-Choice Serial Reaction Time Task (5C-SRTT), an animal model of sustained attention. Adult rats were trained to stably perform the 5C-SRTT and then injected subcutaneously with vehicle or DFP 0.5 mg/kg every other day for 30 days. Behavioral testing occurred daily during the DFP-exposure period and throughout a 45 day (OP-free) washout period. Compared to vehicle-treated controls, DFP-treated rats exhibited deficits in accuracy, increases in omissions and timeout responses during the OP exposure period, while no significant effects on premature responses, perseverative responses, or response latencies were noted. While the increase in timeout responses remained detectible during washout, all other DFP-related alterations in 5C-SRTT performance abated. When the demands of the task were increased by the presentation of variable intertrial intervals, premature responses were also elevated in DFP-treated rats during the washout period. These results indicate that repeated exposures to subthreshold doses of DFP lead to reversible impairments in sustained attention as well as persistent impairments of inhibitory response control in rats. PMID:24819591

  17. Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release.

    PubMed

    Chávez, Jaime; Segura, Patricia; Vargas, Mario H; Arreola, José Luis; Flores-Soto, Edgar; Montaño, Luis M

    2007-04-01

    Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+) measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, omega-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of approximately 50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the

  18. Microbial Community Responses to Organophosphate Substrate Additions in Contaminated Subsurface Sediments

    PubMed Central

    Martinez, Robert J.; Wu, Cindy H.; Beazley, Melanie J.; Andersen, Gary L.; Conrad, Mark E.; Hazen, Terry C.; Taillefert, Martial; Sobecky, Patricia A.

    2014-01-01

    Background Radionuclide- and heavy metal-contaminated subsurface sediments remain a legacy of Cold War nuclear weapons research and recent nuclear power plant failures. Within such contaminated sediments, remediation activities are necessary to mitigate groundwater contamination. A promising approach makes use of extant microbial communities capable of hydrolyzing organophosphate substrates to promote mineralization of soluble contaminants within deep subsurface environments. Methodology/Principal Findings Uranium-contaminated sediments from the U.S. Department of Energy Oak Ridge Field Research Center (ORFRC) Area 2 site were used in slurry experiments to identify microbial communities involved in hydrolysis of 10 mM organophosphate amendments [i.e., glycerol-2-phosphate (G2P) or glycerol-3-phosphate (G3P)] in synthetic groundwater at pH 5.5 and pH 6.8. Following 36 day (G2P) and 20 day (G3P) amended treatments, maximum phosphate (PO4 3−) concentrations of 4.8 mM and 8.9 mM were measured, respectively. Use of the PhyloChip 16S rRNA microarray identified 2,120 archaeal and bacterial taxa representing 46 phyla, 66 classes, 110 orders, and 186 families among all treatments. Measures of archaeal and bacterial richness were lowest under G2P (pH 5.5) treatments and greatest with G3P (pH 6.8) treatments. Members of the phyla Crenarchaeota, Euryarchaeota, Bacteroidetes, and Proteobacteria demonstrated the greatest enrichment in response to organophosphate amendments and the OTUs that increased in relative abundance by 2-fold or greater accounted for 9%–50% and 3%–17% of total detected Archaea and Bacteria, respectively. Conclusions/Significance This work provided a characterization of the distinct ORFRC subsurface microbial communities that contributed to increased concentrations of extracellular phosphate via hydrolysis of organophosphate substrate amendments. Within subsurface environments that are not ideal for reductive precipitation of uranium, strategies that

  19. Role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to organophosphate pesticides.

    PubMed

    Singh, Satyender; Kumar, Vivek; Vashisht, Kapil; Singh, Priyanka; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Rai, Arvind

    2011-11-15

    Organophosphate pesticides (OPs) are primarily metabolized by several xenobiotic metabolizing enzymes (XMEs). Very few studies have explored genetic polymorphisms of XMEs and their association with DNA damage in pesticide-exposed workers. The present study was designed to determine the role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to OPs. We examined 284 subjects including 150 workers occupationally exposed to OPs and 134 normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using PCR-RFLP. The results revealed that the PONase activity toward paraoxonase and AChE activity was found significantly lowered in workers as compared to control subjects (p<0.001). Workers showed significantly higher DNA damage compared to control subjects (14.37±2.15 vs. 6.24±1.37 tail% DNA, p<0.001). Further, the workers with CYP2D6*3PM and PON1 (QQ and MM) genotypes were found to have significantly higher DNA damage when compared to other genotypes (p<0.05). In addition, significant increase in DNA damage was also observed in workers with concomitant presence of certain CYP2D6 and PON1 (Q192R and L55M) genotypes which need further extensive studies. In conclusion, the results indicate that the PON1 and CYP2D6 genotypes can modulate DNA damage elicited by some OPs possibly through gene-environment interactions. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Toxicity hazard of organophosphate insecticide malathion identified by in vitro methods.

    PubMed

    Jira, David; Janousek, Stanislav; Pikula, Jiri; Vitula, Frantisek; Kejlova, Kristina

    2012-01-01

    Malathion is generally not classified as toxic. However, the toxicity seems to be species-dependent. Local and systemic toxicity data for birds are rare, but a decrease of wild bird densities in areas where malathion was applied was reported. Aim of the study was to extend knowledge on malathion toxicity on cellular and organ level and to evaluate embryotoxicity and genotoxicity for birds using the chick embryo model HET-CAM. Skin and eye irritation was determined using reconstructed skin and eye cornea tissues and the chorioallantoic membrane of chick embryo to simulate conjunctiva. Cytotoxicity in 3T3 Balb/c fibroblast culture was determined to estimate acute systemic toxicity. Chick embryo model was further employed to evaluate acute embryotoxicity for birds (mortality and genotoxicity). Data were analysed by means of general linear models. Malathion is not a skin and eye irritant. Cytotoxicity in vitro test provided LD50 value of 616 mg/kg suggesting higher toxic potential than is generally published based on in vivo tests on laboratory rodents. Embryotoxicity studies revealed dose and age dependent mortality of chick embryos. Genotoxicity was identified by means of micronucleus test in erythroid cells isolated from chorioallantois vascular system of chick embryos. Using in vitro alternative toxicological methods, a higher toxic potential of malathion was demonstrated than is generally declared. An increased health and environmental hazard may occur in areas with intensive agricultural production. The environmental consequences of delayed effects and embryotoxicity for bird populations in areas exposed to organophosphate insecticides, such as malathion, are obvious.

  1. Neurological disruption produced in hens by two organophosphate esters

    PubMed Central

    Baron, R. L.; Johnson, H.

    1964-01-01

    A histological and enzymatic examination was made of the neurological disruption produced in hens by two organophosphate esters. Intraperitoneal administration of DEF (tributyl phosphorotrithiolate) and Merphos (tributyl phosphorotrithioite) produced central and perpheral nervous system lesions accompanied by clinical signs of ataxia similar to those seen following administration of tri-o-cresyl phosphate. Histological examination (utilizing the Marchi stain) showed the occurence of spinal cord disruption before the onset of clinical ataxia. Oral administration of DEF and Merphos did not induce signs of peripheral weakness. However, severe lesions in the spinal cord and sciatic nerve were prominent. A discussion of the occurrence of central and peripheral nerve disruption either in the presence or absence of clinical ataxia is presented. Enzymatic examination of the effect of DEF on spinal cord and brain esterases at various intervals following administration showed a pattern of esterase inhibition similar to that found after tri-o-cresyl phosphate, dyflos and other organophosphates. Some prolonged inhibition is believed due to the extent of initial involvement rather than to selective prolonged inhibition. ImagesFig. 1Fig. 2 PMID:14228131

  2. Developmental neurotoxicity targeting hepatic and cardiac sympathetic innervation: effects of organophosphates are distinct from those of glucocorticoids.

    PubMed

    Seidler, Frederic J; Slotkin, Theodore A

    2011-05-30

    Early-life exposure to organophosphate pesticides leads to subsequent hyperresponsiveness of β-adrenergic receptor-mediated cell signaling that regulates hepatic gluconeogenesis, culminating in metabolic abnormalities resembling prediabetes. In the current study, we evaluated the effects of chlorpyrifos or parathion on presynaptic sympathetic innervation to determine whether the postsynaptic signaling effects are accompanied by defects in neuronal input. We administered either chlorpyrifos or parathion to newborn rats using exposure paradigms known to elicit the later metabolic changes but found no alterations in either hepatic or cardiac norepinephrine levels in adolescence or adulthood. However, shifting chlorpyrifos exposure to the prenatal period did evoke changes: exposure early in gestation produced subsequent elevations in norepinephrine, whereas later gestational exposure produced significant deficits. We also distinguished the organophosphate effects from those of the glucocorticoid, dexamethasone, a known endocrine disruptor that leads to later-life metabolic and cardiovascular disruption. Postnatal exposure to dexamethasone elicited deficits in peripheral norepinephrine levels but prenatal exposure did not. Our results indicate that early-life exposure to organophosphates leads to subsequent abnormalities of peripheral sympathetic innervation through mechanisms entirely distinct from those of glucocorticoids, ruling out the possibility that the organophosphate effects are secondary to stress or disruption of the HPA axis. Further, the effects on innervation were separable from those on postsynaptic signaling, differing in critical period as well as tissue- and sex-selectivity. Organophosphate targeting of both presynaptic and postsynaptic β-adrenergic sites, each with different critical periods of vulnerability, thus sets the stage for compounding of hepatic and cardiac functional abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Myopia and Exposure to Organophosphate and Pyrethroid Pesticides in the General United States Population.

    PubMed

    Migneron-Foisy, Vincent; Bouchard, Maryse F; Freeman, Ellen E; Saint-Amour, Dave

    2017-09-01

    Previous research suggests that exposure to pesticides might be associated with human myopia, although data were obtained only from highly exposed individuals. The present study aimed to assess whether exposure to organophosphates and pyrethroids in the United States general population was associated with the prevalence of myopia. Data were obtained from the National Health and Nutrition Examination Survey (NHANES, years 1999-2008). One-spot urine samples were used to estimate the concentration of several pesticide metabolites. Exposure data and equivalent spherical refraction errors were available for 5147 and 2911 individuals for organophosphates and pyrethroids, respectively. Multiple logistic regression models were used to assess the relation between log10-transformed urinary levels of pesticide metabolites and the risk of moderate (≤-1 and >-5 diopters [D]) and high myopia (≤-5 D) in adolescents (12- to 19-years old) and young adults (20- to 40-years old). Models were adjusted for sex, age, ethnicity, diabetes, creatinine, cadmium and lead concentrations, and income in both age groups, but also for education level and cigarette and alcohol consumption in the adult group. No association between organophosphates or pyrethroid metabolites and myopia was observed. However, after adjusting for education level and cigarette and alcohol consumption, a statistically significant decreased risk of high myopia in those with a 10-fold increase of dialkyl phosphate metabolites was found in adults but only in men (P < 0.05). Our results suggest that exposure to organophosphates or pyrethroids do not increase the risk of myopia in the United States general population.

  4. Pharmacotherapy to protect the neuromuscular junction after acute organophosphorus pesticide poisoning.

    PubMed

    Bird, Steven B; Krajacic, Predrag; Sawamoto, Keigo; Bunya, Naofumi; Loro, Emanuele; Khurana, Tejvir S

    2016-06-01

    Organophosphorus (OP) pesticide poisoning is a leading cause of morbidity and mortality in the developing world, affecting an estimated three million people annually. Much of the morbidity is directly related to muscle weakness, which develops 1-4 days after poisoning. This muscle weakness, termed the intermediate syndrome (IMS), leads to respiratory, bulbar, and proximal limb weakness and frequently necessitates the use of mechanical ventilation. While not entirely understood, the IMS is most likely due to persistently elevated acetylcholine (ACh), which activates nicotinic ACh receptors at the neuromuscular junction (NMJ). Thus, the NMJ is potentially a target-rich area for the development of new therapies for acute OP poisoning. In this manuscript, we discuss what is known about the IMS and studies investigating the use of nicotinic ACh receptor antagonists to prevent or mitigate NMJ dysfunction after acute OP poisoning. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  5. Organophosphate poisoning in Rhodesia. A study of the clinical features and management of 105 patients.

    PubMed

    Hayes, M M; van der Westhuizen, N G; Gelfand, M

    1978-08-05

    A series of 105 patients with organophosphate poisoning admitted to Harari Hospital during the past 4 years is described. Poisoning with organophosphate compounds is being seen more frequently in hospital practice in Rhodesia. Many of the cases are attempted suicides, but frequently there is no positive history of contact with the poison. The majority of patients exhibit the classic clinical features of parasympathetic overactivity, but diagnosis may be obscured by atypical presentation. Rapid diagnosis and utilization of the treatment regimen outlined in this article should reduce the mortality to less than 15%.

  6. Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum

    PubMed Central

    Torres-Altoro, Melissa I.; Mathur, Brian N.; Drerup, Justin M.; Thomas, Rachel; Lovinger, David; O’Callaghan, James P.; Bibb, James A.

    2011-01-01

    The neurological effects of organophosphate pesticides, commonly used on foods and in households, are an important public health concern. Furthermore, subclinical exposure to combinations of organophosphates is implicated in Gulf War illness. Here we characterized the effects of the broadly-used insecticide chlorpyrifos on dopamine and glutamatergic neurotransmission effectors in corticostriatal motor/reward circuitry. Chlorpyrifos potentiated PKA-dependent phosphorylation of the striatal protein DARPP-32 and the GluR1 subunit of AMPA receptors in mouse brain slices. It also increased GluR1 phosphorylation by PKA when administered systemically. This correlated with enhanced glutamate release from cortical projections in rat striatum. Similar effects were induced by the sarin congener, diisopropyl fluorophosphate, alone or in combination with the putative neuroprotectant, pyridostigmine bromide and the pesticide DEET. This combination, meant to mimic the neurotoxicant exposure encountered by veterans of the 1991 Persian Gulf War, also induced hyperphosphorylation of the neurofibrillary tangle-associated protein tau. Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination, also increased the aberrant activity of the protein kinase, Cdk5, as indicated by conversion of its activating cofactor p35 to p25. Thus consistent with recent findings in humans and animals, organophosphate exposure causes dysregulation in the motor/reward circuitry and invokes mechanisms associated with neurological disorders and neurodegeneration. PMID:21848865

  7. Blood Neuropathy Target Esterase as Biochemical Marker for Neuropathic Organophosphates Exposure

    DTIC Science & Technology

    2001-09-01

    E-mail gmakh(@ipac.ac.ru2Faculty of Chemistry, M.V. Lomonosov Moscow State University, Moscow, 119899, Russia;3Research Center for Molecular ... Diagnostics and Therapy, Moscow, 113149, Russia. INTRODUCTION Organophosphate-induced delayed neurotoxicity (OPIDN) is a distal degeneration of sensory and

  8. Population-Based Biomonitoring of Exposure to Organophosphate and Pyrethroid Pesticides in New York City

    PubMed Central

    Jacobson, J. Bryan; Kass, Daniel; Barr, Dana Boyd; Davis, Mark; Calafat, Antonia M.; Aldous, Kenneth M.

    2013-01-01

    Background: Organophosphates and pyrethroids are the most common classes of insecticides used in the United States. Widespread use of these compounds to control building infestations in New York City (NYC) may have caused higher exposure than in less-urban settings. Objectives: The objectives of our study were to estimate pesticide exposure reference values for NYC and identify demographic and behavioral characteristics that predict exposures. Methods: The NYC Health and Nutrition Examination Survey was a population-based, cross-sectional study conducted in 2004 among adults ≥ 20 years of age. It measured urinary concentrations of organophosphate metabolites [dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate, diethylphosphate, diethylthiophosphate, and diethyldithiophosphate] in 883 participants, and pyrethroid metabolites [3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (trans-DCCA), 4-fluoro-3-phenoxybenzoic acid, and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid] in 1,452 participants. We used multivariable linear regression to estimate least-squares geometric mean total dialkylphospate (ΣDAP) and 3-PBA concentrations across categories of predictors. Results: The dimethyl organophosphate metabolites had the highest 95th percentile concentrations (87.4 μg/L and 74.7 μg/L for DMP and DMTP, respectively). The highest 95th percentiles among pyrethroid metabolites were measured for 3-PBA and trans-DCCA (5.23 μg/L and 5.94 μg/L, respectively). Concentrations of ΣDAP increased with increasing age, non-Hispanic white or black compared with Hispanic race/ethnicity, professional pesticide use, and increasing frequency of fruit consumption; they decreased with non-green vegetable consumption. Absolute differences in geometric mean urinary 3-PBA concentrations across categories of predictors were too small to be meaningful. Conclusion: Estimates of exposure to

  9. Farmworker and nonfarmworker Latino immigrant men in North Carolina have high levels of specific pesticide urinary metabolites.

    PubMed

    Arcury, Thomas A; Chen, Haiying; Laurienti, Paul J; Howard, Timothy D; Barr, Dana Boyd; Mora, Dana C; Quandt, Sara A

    2017-06-16

    This article compares detections and concentrations of specific organophosphate (OP), bis-dithiocarbamate, and pyrethroid pesticide urinary metabolites among Latino male farmworkers and nonfarmworkers in North Carolina. Data are from interviews and urine samples collected in 2012 and 2013. Farmworkers and nonfarmworkers frequently had detections for OP and pyrethroid pesticide urinary metabolites. Detection of bis-dithiocarbamate urinary metabolites was less frequent, but substantial among the nonfarmworkers. The concentrations of organophosphate, bis-dithiocarbamate, and pyrethroid pesticide urinary metabolites were high for farmworkers and nonfarmworkers compared to National Health and Nutrition Examination Survey results. Pesticide urinary metabolite detection was not associated with occupation in nonfarmworkers. Research for reducing pesticide exposure among farmworkers remains important; research is also needed to determine pesticide exposure pathways among Latino nonfarmworkers.

  10. [Acute risk assessment of cumulative dietary exposure to organophosphorus pesticide among people in Jiangsu province].

    PubMed

    Zhao, Minxian; Wang, Cannan; Li, Tingting; Yi, Nannan; He, Xiansong; Wu, Hui; Yao, Xinya

    2013-09-01

    To understand the cumulative dietary exposure of Jiangsu residents to organophosphorus (OPs) pesticide and make acute risk assessment. Integrated the data of the nutrition and health status of residents in Jiangsu and the data of monitoring of OPs pesticide in agricultural products. Chlorpyrifos was selected as index compound (index chemical, IC), then use relative potency factor (RPF) approach which commended by EPA and simple distribution evaluation. Caloulated the dietary cumulative exposure of OPs pesticide among Jiangsu residents and compared with acute reference dose (ARfD), then made risk assessment. The exposure of rural group of age 3-6 and 7-11 were 133.84 microg/kg BW and 154.32 microg/kg BW, exceeded ARfD. The exposure level of kids and elder was higher than adults. The exposure level of rural residents were higher than urban residents. The highest contribution to the food of each age group was greengrocery and leek. The average level of exposure was safety in Jiangsu, high exposure children were at acute poisoning risk. High contribution food such as greengrocery and leek should be strengthen monitoring.

  11. Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children

    PubMed Central

    Rowe, Christopher; Gunier, Robert; Bradman, Asa; Harley, Kim G.; Kogut, Katherine; Parra, Kimberly; Eskenazi, Brenda

    2016-01-01

    Background Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity. Objectives To examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children. Methods We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression. Results Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = −3.0; 95% Confidence Interval (CI) = (−5.6, −0.3)], Perceptual Reasoning [β = −4.0; (−7.6, −0.4)], and Working Memory [β = −2.8; (−5.6, −0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory. Conclusions Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age. PMID:27281690

  12. Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children.

    PubMed

    Rowe, Christopher; Gunier, Robert; Bradman, Asa; Harley, Kim G; Kogut, Katherine; Parra, Kimberly; Eskenazi, Brenda

    2016-10-01

    Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity. To examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children. We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression. Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [β = -4.0; (-7.6, -0.4)], and Working Memory [β = -2.8; (-5.6, -0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory. Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Validation of a New "Objective Pain Score" Vs. "Numeric Rating Scale" For the Evaluation of Acute Pain: A Comparative Study.

    PubMed

    Tandon, Manish; Singh, Anshuman; Saluja, Vandana; Dhankhar, Mandeep; Pandey, Chandra Kant; Jain, Priyanka

    2016-02-01

    Pain scores are used for acute pain management. The assessment of pain by the patient as well as the caregiver can be influenced by a variety of factors. The numeric rating scale (NRS) is widely used due to its easy application. The NRS requires abstract thinking by a patient to assign a score to correctly reflect analgesic needs, and its interpretation is subject to bias. The study was done to validate a 4-point objective pain score (OPS) for the evaluation of acute postoperative pain and its comparison with the NRS. A total of 1021 paired readings of the OPS and NRS of 93 patients who underwent laparotomy and used patient-controlled analgesia were evaluated. Acute pain service (APS) personnel recorded the OPS and NRS. Rescue analgesia was divided into two incremental levels (level 1-paracetamol 1 g for NRS 2 - 5 and OPS 3, Level 2-Fentanyl 25 mcg for NRS ≥ 6 and OPS 1 and 2). In cases of disagreement between the two scores, an independent consultant decided the rescue analgesia. The NRS and OPS agreed across the range of pain. There were 25 disagreements in 8 patients. On 24 occasions, rescue analgesia was increased from level 1 to 2, and one occasion it was decreased from level 2 to 1. On all 25 occasions, the decision to supplement analgesia went in favor of the OPS over the NRS. Besides these 25 disagreements, there were 17 occasions in which observer bias was possible for level 2 rescue analgesia. The OPS is a good stand-alone pain score and is better than the NRS for defining mild and moderate pain. It may even be used to supplement NRS when it is indicative of mild or moderate pain.

  14. Quantitative structure-activity relationships for organophosphates binding to acetylcholinesterase.

    PubMed

    Ruark, Christopher D; Hack, C Eric; Robinson, Peter J; Anderson, Paul E; Gearhart, Jeffery M

    2013-02-01

    Organophosphates are a group of pesticides and chemical warfare nerve agents that inhibit acetylcholinesterase, the enzyme responsible for hydrolysis of the excitatory neurotransmitter acetylcholine. Numerous structural variants exist for this chemical class, and data regarding their toxicity can be difficult to obtain in a timely fashion. At the same time, their use as pesticides and military weapons is widespread, which presents a major concern and challenge in evaluating human toxicity. To address this concern, a quantitative structure-activity relationship (QSAR) was developed to predict pentavalent organophosphate oxon human acetylcholinesterase bimolecular rate constants. A database of 278 three-dimensional structures and their bimolecular rates was developed from 15 peer-reviewed publications. A database of simplified molecular input line entry notations and their respective acetylcholinesterase bimolecular rate constants are listed in Supplementary Material, Table I. The database was quite diverse, spanning 7 log units of activity. In order to describe their structure, 675 molecular descriptors were calculated using AMPAC 8.0 and CODESSA 2.7.10. Orthogonal projection to latent structures regression, bootstrap leave-random-many-out cross-validation and y-randomization were used to develop an externally validated consensus QSAR model. The domain of applicability was assessed by the William's plot. Six external compounds were outside the warning leverage indicating potential model extrapolation. A number of compounds had residuals >2 or <-2, indicating potential outliers or activity cliffs. The results show that the HOMO-LUMO energy gap contributed most significantly to the binding affinity. A mean training R (2) of 0.80, a mean test set R (2) of 0.76 and a consensus external test set R (2) of 0.66 were achieved using the QSAR. The training and external test set RMSE values were found to be 0.76 and 0.88. The results suggest that this QSAR model can be used in

  15. REMOTE BIOSENSOR FOR IN SITU MONITORING OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

    EPA Science Inventory

    A remote electrochemical biosensor for field monitoring of organophosphate nerve agents is described. The new sensor relies on the coupling of the effective biocatalytic action of organophosphorus hydrolase (OPH) with a submersible amperometric probe design. This combination resu...

  16. RESIDENTIAL PESTICIDE USE AND URINARY ORGANOPHOSPHATE METABOLITES IN PRE-SCHOOL CHILDREN

    EPA Science Inventory

    Residential Pesticide Use and Urinary Organophosphate Metabolites in Pre-School Children
    CL Carty1, P Mendola1, D Barr2, L Needham2, D Walsh1

    1Epidemiology and Biomarkers Branch, Human Studies Division, National Health and Environmental Effects Research Laboratory, U.S....

  17. Proteomic analysis of Trichoderma atroviride mycelia stressed by organophosphate pesticide dichlorvos.

    PubMed

    Tang, Jun; Liu, Lixing; Huang, Xiuli; Li, Yingying; Chen, Yunpeng; Chen, Jie

    2010-02-01

    The proteomic approach is a powerful tool to study microbial response to environmental stress. To evaluate the responses of Trichoderma spp. to the organophosphate pesticide dichlorvos, mycelia of Trichoderma atroviride T23 were exposed to dichlorvos at concentrations of 0, 100, 300, 500, and 1000 microg/mL, respectively. Changes in protein expression were investigated using two-dimensional sodium dodecyl sulfate - polyacrylamide gel electrophoresis. Sixteen protein spots were differentially expressed. They were identified by MALDI-TOF/TOF MS and were found to be linked to energy metabolism, transport, signal transduction, and stress tolerance. Among stress-related proteins, glutathione peroxidase-like protein (GPX), 1,4-benzoquinone reductase, and HEX1 were upregulated by and cyclophilin A induced by 1000 microg/mL dichlorvos when compared with the control. These proteins were considered to be associated with fungal adaptation to adverse conditions. The results will help us to understand molecular mechanisms through which Trichoderma responds to organophosphate pesticides.

  18. Pesticide loadings of select organophosphate and pyrethroid pesticides in urban public housing.

    EPA Science Inventory

    We investigated the magnitude and distribution of pyrethroid and organophosphate pesticide loadings within public housing dwellings in Boston, Massachusetts and compared the results using various sampling methods. We collected dust matrices from living room and kitchen in 42 apar...

  19. Measuring and modeling surface sorption dynamics of organophosphate flame retardants in chambers

    EPA Science Inventory

    Understanding the sorption mechanisms for organophosphate flame retardants (OPFRs) on impervious surfaces is important to improve our understanding of the fate and transport of OPFRs in indoor environments. Langmuir and Freundlich models are widely adopted to describe sorption be...

  20. Orange pomace improves postprandial glycemic responses: an acute, randomized, placebo-controlled, double-blind, crossover trial in overweight men

    USDA-ARS?s Scientific Manuscript database

    Orange pomace (OP), a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-co...

  1. Measuring and Modeling Surface Sorption Dynamics of Organophosphate Flame Retardants in Chambers

    EPA Science Inventory

    Understanding the sorption mechanisms for organophosphate flame retardants (OPFRs) on impervious surfaces is important if we are to improve our understanding of the fate and transport of OPFRs in indoor environments. Traditional Langmuir and Freundlich models are widely adopted t...

  2. Urinary concentrations of organophosphate and carbamate pesticides in residents of a vegetarian community.

    PubMed

    Berman, T; Göen, T; Novack, L; Beacher, L; Grinshpan, L; Segev, D; Tordjman, K

    2016-11-01

    Few population studies have measured urinary levels of pesticides in individuals with vegan, vegetarian, or organic diets. The objectives of this study were to evaluate whether a vegan/vegetarian diet was associated with increased exposure to organophosphate and carbamate pesticides, and to evaluate the impact of organic consumption on pesticide exposure in vegans and vegetarians. In the current pilot study conducted in 2013-2014, we collected spot urine samples and detailed 24h recall dietary data in 42 adult residents of Amirim, a vegetarian community in Northern Israel. We measured urinary levels of non-specific organophosphate pesticide metabolites (dialkylphosphates, (DAPs)) and specific metabolites of the current-use pesticides chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPy)), propoxur (-isopropoxyphenol (IPPX)), and carbaryl (1-naphthol). Six DAP metabolites were detected in between 67 and 100% of urine samples, with highest geometric mean concentrations for dimethylphosphate (19.2μg/g). Creatinine-adjusted median concentrations of total DAPs and of TCPy were significantly higher in Amirim residents compared to the general Jewish population in Israel (0.29μmol/g compared to 0.16, p<0.05 for DAPs and 4.32μg/g compared to 2.34μg/g, p<0.05 for TCPy). Within Amirim residents, we observed a positive association between vegetable intake and urinary TCPy levels (rho=0.47, p<0.05) and lower median total dimethyl phosphate levels in individuals reporting that >25% of the produce they consume is organic (0.065μmol/L compared to 0.22, p<0.05). Results from this pilot study indicate relatively high levels of urinary organophosphate pesticide metabolite concentrations in residents of a vegetarian community, a positive association between vegetable intake and urinary levels of a chlorpyrifos specific metabolite, and lower levels of total dimethyl phosphate in individuals reporting higher intake of organic produce. Results suggest that consumption of organic produce

  3. Malathion

    EPA Pesticide Factsheets

    This organophosphate (OP) insecticide is used in agriculture, residential gardens, public recreation areas, and public health pest control programs. Applied according to label specifications, it can be used to kill mosquitoes without unreasonable risks.

  4. Effects of intralipid and caffeic acid phenethyl ester on neurotoxicity, oxidative stress, and acetylcholinesterase activity in acute chlorpyriphos intoxication

    PubMed Central

    Ozkan, Umit; Osun, Arif; Basarslan, Kagan; Senol, Serkan; Kaplan, Ibrahim; Alp, Harun

    2014-01-01

    Chlorpyriphos is one of the most widely used organophosphate (OP) insecticide in agriculture with potential toxicity. Current post-exposure treatments consist of anti-cholinergic drugs and oxime compounds. We studied the effects of intralipid and caffeic acid phenethyl ester (CAPE) on chlorpyriphos toxicity to compose an alternative or supportive treatment for OP poisoning. Methods: Forty-nine rats were randomly divided into seven groups. Chlorpyriphos was administered for toxicity. Intralipid (IL) and CAPE administered immediately after chlorpyriphos. Serum acetylcholinesterase (AChE) level, total oxidant status (TOS), total antioxidant response (TAR), and histologic examination of cerebellum and brain tissue with Hematoxylin-Eosin and immunohistochemical dyes were examined. Results: Serum enzym levels showed that chlorpyriphos and CAPE inhibited AChE while IL alone had no effect, chlorpyriphos and CAPE intensifies the inhibition effect. Significant difference at AChE levels between the chlorpyriphos+IL and chlorpyriphos+CAPE verified that IL has a protective effect on AChE inhibition. TAR levels were significantly increased in all groups except chlorpyriphos group, TOS levels revealed that CAPE and IL decrease the amount of oxidative stress. Histologic examination revealed that neuronal degeneration was slightly decreased at chlorpyriphos+IL group, but CAPE had a significant effect on protection of neuronal degeneration. Conclusion: The results of this study gave us three key points. 1) AChE activity is important for diagnosis of OP intoxication but it has no value for determining the neuro-degeneration. 2) CAPE inhibits AChE activity and may increase the muscarinic-nicotinic hyperactivation. Therefore it should not be used for treatment of OP intoxication. 3) IL decreases the severity of neurodegeneration and symptoms of OP intoxication and it can be used as a supportive agent. PMID:24955152

  5. Screening of the presence organophosphates and organochlorines pesticide residues in vegetables and fruits using gas chromatography-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Putri, Dillani; Aryana, Nurhani; Aristiawan, Yosi; Styarini, Dyah

    2017-01-01

    Pesticides is commonly used to improve the quality of agricultural product, especially in vegetables and fruits. Due to pesticide residues in the product become a concern to consumer health, monitoring and analysis of pesticide residues in agriculture product need to be established. The certified reference material (CRM) is often benefited to obtain accurate results in analysis. It is required as the quality control to improve quality assurance of the testing results. Unfortunately in Indonesia, the development of matrix CRM for the analysis of pesticide residues in vegetables and fruits is still limited. This study is aimed to determine the type of commodity and target analyte to be employed in the development of CRM for pesticides in vegetables and fruits. As the preliminary study, the screening of 11 commodities of fresh vegetables and fruits has been conducted to review the information about the presence of organophosphates (OPs) and organochlorines (OCs) in the sample. In this analysis, QuEChERS technique was used in the extraction process and the qualitative analysis was evaluated by using GC-MS. The results showed that strawberry and celery contain residues of pesticide chlorpyrifos. Further analysis of the commodity celery from seven different places has been conducted, resulting that from 3 of all 7 samples (43%) were positive containing chlorpyrifos. Therefore, the development of CRM for chlorpyrifos in celery will be our next research project.

  6. Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication.

    PubMed

    Faria, Melissa; Prats, Eva; Padrós, Francesc; Soares, Amadeu M V M; Raldúa, Demetrio

    2017-04-01

    Acute organophosphorus (OP) intoxication is a worldwide clinical and public health problem. In addition to cholinergic crisis, neurodegeneration and brain damage are hallmarks of the severe form of this toxidrome. Recently, we generated a chemical model of severe acute OP intoxication in zebrafish that is characterized by altered head morphology and brain degeneration. The pathophysiological pathways resulting in brain toxicity in this model are similar to those described in humans. The aim of this study was to assess the predictive power of this zebrafish model by testing the effect of a panel of drugs that provide protection in mammalian models. The selected drugs included "standard therapy" drugs (atropine and pralidoxime), reversible acetylcholinesterase inhibitors (huperzine A, galantamine, physostigmine and pyridostigmine), N-methyl-D-aspartate (NMDA) receptor antagonists (MK-801 and memantine), dual-function NMDA receptor and acetylcholine receptor antagonists (caramiphen and benactyzine) and anti-inflammatory drugs (dexamethasone and ibuprofen). The effects of these drugs on zebrafish survival and the prevalence of abnormal head morphology in the larvae exposed to 4 µM chlorpyrifos oxon [1 × median lethal concentration (LC 50 )] were determined. Moreover, the neuroprotective effects of pralidoxime, memantine, caramiphen and dexamethasone at the gross morphological level were confirmed by histopathological and transcriptional analyses. Our results demonstrated that the zebrafish model for severe acute OP intoxication has a high predictive value and can be used to identify new compounds that provide neuroprotection against severe acute OP intoxication.

  7. Validation of a New “Objective Pain Score” Vs. “Numeric Rating Scale” For the Evaluation of Acute Pain: A Comparative Study

    PubMed Central

    Tandon, Manish; Singh, Anshuman; Saluja, Vandana; Dhankhar, Mandeep; Pandey, Chandra Kant; Jain, Priyanka

    2016-01-01

    Background: Pain scores are used for acute pain management. The assessment of pain by the patient as well as the caregiver can be influenced by a variety of factors. The numeric rating scale (NRS) is widely used due to its easy application. The NRS requires abstract thinking by a patient to assign a score to correctly reflect analgesic needs, and its interpretation is subject to bias. Objectives: The study was done to validate a 4-point objective pain score (OPS) for the evaluation of acute postoperative pain and its comparison with the NRS. Patient and Methods: A total of 1021 paired readings of the OPS and NRS of 93 patients who underwent laparotomy and used patient-controlled analgesia were evaluated. Acute pain service (APS) personnel recorded the OPS and NRS. Rescue analgesia was divided into two incremental levels (level 1-paracetamol 1 g for NRS 2 - 5 and OPS 3, Level 2-Fentanyl 25 mcg for NRS ≥ 6 and OPS 1 and 2). In cases of disagreement between the two scores, an independent consultant decided the rescue analgesia. Results: The NRS and OPS agreed across the range of pain. There were 25 disagreements in 8 patients. On 24 occasions, rescue analgesia was increased from level 1 to 2, and one occasion it was decreased from level 2 to 1. On all 25 occasions, the decision to supplement analgesia went in favor of the OPS over the NRS. Besides these 25 disagreements, there were 17 occasions in which observer bias was possible for level 2 rescue analgesia. Conclusions: The OPS is a good stand-alone pain score and is better than the NRS for defining mild and moderate pain. It may even be used to supplement NRS when it is indicative of mild or moderate pain. PMID:27110530

  8. Impact of organophosphate exposure on farmers’ health in Kulon Progo, Yogyakarta: Perspectives of physical, emotional and social health

    PubMed Central

    Perwitasari, Dyah Aryani; Prasasti, Dian; Supadmi, Woro; Jaikishin, Sonia Amelia Dewi; Wiraagni, Idha Arfianti

    2017-01-01

    Objective: The exposure of organophosphate could be caused by the absorption in some parts of the body like skin and breath. Toxicity may cause nausea, vomiting and dizziness which are not too specific related with the pesticide toxicity. The purpose of this study is to understand the association between organophosphate exposure and farmers’ health in Kulon Progo County from the perspectives of physical, emotional and social health. Methods: This study was conducted using descriptive observational design. The blood sample was collected during harvesting periods in 2016. The inclusion criterion of farmers was using organophosphate-contained pesticide during the planting period of red onion. The farmers who had renal disease, liver disease and cancer were excluded. The organophosphate exposure parameters were the duration and frequency of pesticide application, width of the area, serum cholinesterase activity and the completeness of personal protective equipment. Results: Among 84 farmers, most of them were male (85.7%), and the mean age was 49.1 (standard deviation: 12.5) years; 71.4% of the subjects experienced tremor, 17.86% experienced dizziness and 8.33% subjects experienced nausea–vomiting after pesticide application. According to the pesticide application, in average, subjects used pesticide 1.4 h/day with the area of 1.285 m2. The frequency of pesticide used is three times per week. Around 97.6% subjects used incomplete personal protective equipment. The average of serum cholinesterase activity in subjects with tremor is higher than subjects without tremor (p > 0.05). There is a significant association between serum cholinesterase activity and creatinine content (p < 0.05). The farmers’ quality-of-life domain scores are lower than the scores of the normal population in Yogyakarta. Conclusion: Organophosphate exposure may affect the farmers’ physical health and quality of life. PMID:28839934

  9. Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Organophosphate Test System. Final order.

    PubMed

    2017-10-18

    The Food and Drug Administration (FDA or we) is classifying the organophosphate test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the organophosphate test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

  10. FIBER-OPTIC BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

    EPA Science Inventory

    A fiber-optic enzyme biosensor for the direct measurement of organophosphate nerve
    agents was developed. The basic element of this biosensor is organophosphorus hydrolase
    immobilized on a nylon membrane and attached to the common end of a bifurcated optical fiber
    bundle....

  11. Potential clinical application of surface electromyography as indicator of neuromuscular recovery during weaning tests after organophosphate poisoning.

    PubMed

    Sánchez, Maria Bernarda Salazar; Valdivieso, Alher Mauricio Hernández; Villanueva, Miguel Ángel Mañanas; Salazar, Andrés Felipe Zuluaga

    2017-01-01

    This study aimed to explore the usefulness of measuring respiratory muscle activity in mechanically ventilated patients suffering from acute organophosphate poisoning, with a view towards providing complementary information to determine the best time to suspend ventilatory support. Surface electromyography in respiratory muscles (diaphragm, external intercostal and sternocleidomastoid muscles) was recorded in a young man affected by self-poisoning with an unknown amount of parathion to determine the muscle activity level during several weaning attempts from mechanical ventilation. The energy distribution of each surface electromyography signal frequency, the synchronization between machine and patient and between muscles, acetylcholinesterase enzyme activity, and work of breathing and rapid shallow breathing indices were calculated in each weaning attempt. The work of breathing and rapid shallow breathing indices were not correlated with the failure/success of the weaning attempt. The diaphragm gradually increased its engagement with ventilation, achieving a maximal response that correlated with successful weaning and maximal acetylcholinesterase enzyme activity; in contrast, the activity of accessory respiratory muscles showed an opposite trend.

  12. Esterase metabolism of cholinesterase inhibitors using rat liver in vitro

    EPA Science Inventory

    A variety of chemicals, such as organophosphate (OP) and carbamate pesticides, nerve agents, and industrial chemicals, inhibit acetylcholinesterase (AChE) leading to overstimulation of the cholinergic nervous system. The resultant neurotoxicity is similar across mammalian species...

  13. Esterase detoxification of acetylcholinesterase inhibitors by human or rat liver in vitro

    EPA Science Inventory

    Organophosphate (OP) and N-methylcarbamate pesticides inhibit acetylcholinesterase (AChE), but differences in metabolism and detoxification can influence potency of these pesticides across and within species. Carboxylesterase (CaE) and A-esterase (paraoxonase, PON) are considered...

  14. Genetic engineering approach to toxic waste management: case study for organophosphate waste treatment.

    PubMed

    Coppella, S J; DelaCruz, N; Payne, G F; Pogell, B M; Speedie, M K; Karns, J S; Sybert, E M; Connor, M A

    1990-01-01

    Currently, there has been limited use of genetic engineering for waste treatment. In this work, we are developing a procedure for the in situ treatment of toxic organophosphate wastes using the enzyme parathion hydrolase. Since this strategy is based on the use of an enzyme and not viable microorganisms, recombinant DNA technology could be used without the problems associated with releasing genetically altered microorganisms into the environment. The gene coding for parathion hydrolase was cloned into a Streptomyces lividans, and this transformed bacterium was observed to express and excrete this enzyme. Subsequently, fermentation conditions were developed to enhance enzyme production, and this fermentation was scaled-up to the pilot scale. The cell-free culture fluid (i.e., a nonpurified enzyme solution) was observed to be capable of effectively hydrolyzing organophosphate compounds under laboratory and simulated in situ conditions.

  15. Prophylaxis against Organophosphorous Nerve Agents - State of the Art (profylaxe tegen organofosfaat zenuwgassen - stand van zaken)

    DTIC Science & Technology

    2005-12-01

    consists of those that catalytically hydrolyze (in some cases stereoselectively) OP’s into non-toxic alkyl methyl phosphonic acids. These enzymes are so...8217fluorosphatase’, nowadays known as OPH, capable of hydrolyzing organophosphates. For therapy and/or profylaxis, a hydrolytic enzyme could be...HuPON hydrolyzes OP insecticides and nerve gases and a relationship was found between the amount of enzyme in different species and the toxic response

  16. Proceedings of the AMEDD Psychology Symposium Held at Washington, DC on 27-31 October 1980

    DTIC Science & Technology

    1983-12-01

    more toxic pesticides . In fact, so rapid was this development that the possibilities of modern chemical warfare were foreseen by 1899. An international...cases of "severe" exposure to organophosphate (OP) pesticides (compounds similar in action to NA) the prominent symptoms were vomiting, abdominal pain...exposures to OP pesticides . Some severe exposure cases showed an inability to remember street and phone numbers and were unable to recognize old friends

  17. Contributing Factors for Morbidity and Mortality in Patients with Organophosphate Poisoning on Mechanical Ventilation: A Retrospective Study in a Teaching Hospital

    PubMed Central

    Patil, Gurulingappa; Nikhil, M.

    2016-01-01

    Introduction One of the most common causes of poisoning in agricultural based developing countries like India is due to Organophosphorus (OP) compound. Its widespread use and easy availability has increased the likelihood of poisoning with these compounds. Aim To study the morbidity and mortality in patients with acute OP poisoning requiring mechanical ventilation. Materials and Methods This was a retrospective study constituting patients of all age groups admitted to the Intensive Care Unit (ICU) with diagnosis of OP poisoning between January 2015 to December 2015. Of 66 OP poisoning cases those patients who went against medical advice, 20 were excluded from the study and thus 46 patients were included. Diagnosis was performed from the history taken either from the patient or from the patient’s relatives and presenting symptoms. Demographic data, month of the year, age of patient, mode of poisoning, cholinesterase levels, duration of mechanical ventilation and mortality were recorded. Data are presented as mean±SD. Results A 97.83% (45/46) of cases were suicidal. Out of 46, 9 were intubated and mechanically ventilated. Duration of mechanical ventilation varied from less than 48 hours to more than 7 days. Mortality rate was 50%, 0% and 100% in those who required mechanical ventilation for more than 7 days, 2 to 7 days and <2days respectively. None of the predictors like age, severity of poisoning, cholinesterase levels and duration of ventilation were independent predictors of death and all of them contributed to the mortality. Overall mortality rate in those who required mechanical ventilation was 22.22%. Conclusion Morbidity and mortality due to OP poisoning is directly proportional to the age, severity of poisoning and duration of mechanical ventilation and inversely proportional to serum cholinesterase level. PMID:28208980

  18. [Organophosphate pesticides and neuropsychological and motor effects in the Maule Region, Chile].

    PubMed

    Muñoz-Quezada, María Teresa; Lucero, Boris; Iglesias, Verónica; Muñoz, María Pía; Achú, Eduardo; Cornejo, Claudia; Concha, Carlos; Grillo, Angela; Brito, Ana María

    2016-01-01

    To evaluate organophosphate pesticide exposure and neuropsychological and motor performance in agricultural and non-agricultural workers in the Maule Region in Chile. Analytic cross-sectional study in 93 exposed farm workers and 84 unexposed non-agricultural workers. A battery of four neuropsychological tests was administered together with a neuro-motor physical examination. On the Weschler adult intelligence scale (WAIS-IV), exposed agricultural workers exhibited poorer performance than non-agricultural workers in verbal comprehension (β=-3.2; p=0.034) and processing speed (β=-4.4; p=0.036) and in the full scale (β=-4; p=0.016), as well as in discrimination sensitivity (β=1, p=0,009), adjusted by years of schooling and/or age. We suggest the development of policies and regulations for the control, sale and use of organophosphate pesticides and intervention strategies on safety measures aimed at the exposed population. Copyright © 2016 SESPAS. Published by Elsevier Espana. All rights reserved.

  19. Esterase detoxification of acetylcholinesterase inhibitors using human liver samples in vitro

    EPA Science Inventory

    Organophosphate (OP) and N-methylcarbamate pesticides inhibit acetylcholinesterase (AChE), but differences in metabolism and detoxification can influence potency of these pesticides across and within species. Carboxylesterase (CaE) and A-esterase (paraoxonase, PON1) are consider...

  20. Role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to organophosphate pesticides

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Singh, Satyender; Kumar, Vivek; Vashisht, Kapil

    2011-11-15

    Organophosphate pesticides (OPs) are primarily metabolized by several xenobiotic metabolizing enzymes (XMEs). Very few studies have explored genetic polymorphisms of XMEs and their association with DNA damage in pesticide-exposed workers. The present study was designed to determine the role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to OPs. We examined 284 subjects including 150 workers occupationally exposed to OPs and 134 normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using PCR-RFLP. The results revealed that the PONase activitymore » toward paraoxonase and AChE activity was found significantly lowered in workers as compared to control subjects (p < 0.001). Workers showed significantly higher DNA damage compared to control subjects (14.37 {+-} 2.15 vs. 6.24 {+-} 1.37 tail% DNA, p < 0.001). Further, the workers with CYP2D6*3 PM and PON1 (QQ and MM) genotypes were found to have significantly higher DNA damage when compared to other genotypes (p < 0.05). In addition, significant increase in DNA damage was also observed in workers with concomitant presence of certain CYP2D6 and PON1 (Q192R and L55M) genotypes which need further extensive studies. In conclusion, the results indicate that the PON1 and CYP2D6 genotypes can modulate DNA damage elicited by some OPs possibly through gene-environment interactions. -- Highlights: Black-Right-Pointing-Pointer Role of CYP1A1, CYP3A5, CYP2C, CYP2D6 and PON1 genotypes on DNA damage. Black-Right-Pointing-Pointer Workers exposed to some OPs demonstrated increased DNA damage. Black-Right-Pointing-Pointer CYP2D6 *3 PM and PON1 (Q192R and L55M) genotypes are associated with DNA damage. Black-Right-Pointing-Pointer Concomitant presence of certain CYP2D6 and PON1 genotypes can increase DNA damage.« less

  1. Organophosphate Urinary Metabolite Levels during Pregnancy, Delivery and Postpartum in Women Living in Agricultural Areas in Thailand

    PubMed Central

    Kongtip, Pornpimol; Nankongnab, Noppanun; Woskie, Susan; Phamonphon, Akkarat; Tharnpoophasiam, Prapin; Wilaiwan, Kitsiluck; Srasom, Punnee

    2018-01-01

    Organophosphate Urinary Metabolite Levels during Pregnancy, Delivery and Postpartum in Women Living in Agricultural Areas in Thailand: Pornpimol Kongtip, et al. Department of Occupational Health and Safety, Faculty of Public Health, Mahidol University, Thailand Objective Prenatal exposure to organophosphate pesticides can lead to developmental neurotoxicity. A longitudinal birth cohort was established to investigate pesticide exposures from different agricultural activities. Maternal urinary organophosphate metabolites were measured at 28 weeks of pregnancy (n=86), delivery (n=67) and 2 months postpartum (n=51). Method Subjects were interviewed with questionnaires about work, home and behavioral factors potentially associated with pesticide exposures, and spot urine samples were also collected. The urine samples were analyzed for dimethyl phosphate (DMP), diethyl phosphate (DEP), diethyl thiophosphate (DETP) and diethyl dithiophosphate (DEDTP), using gas chromatography-mass spectrometry. Results The urinary DMP and dialkyl phosphate (DAP) concentrations at 28 weeks of pregnancy and delivery were not significantly different, but the DMP and DAP concentrations at 28 weeks of pregnancy and DAP concentrations at delivery were significantly different (p<0.05) from those at 2 months postpartum. The factors influencing the urinary DAP concentrations at 28 weeks of pregnancy included insecticide used in the home, living close to agricultural farmland, frequency of agricultural field visits during the first and second trimesters of pregnancies, occupation of subjects, pesticide used and other agricultural activities. Conclusions The urinary organophosphate metabolites, DMP, DEP, DETP, DEDTP, total DEP and DAPs, at 28 weeks of pregnancy, delivery and 2 months postpartum fluctuated depending on their pesticide exposures both at home and in agricultural fields. PMID:23892639

  2. COMPARING PESTICIDE TRANSFERS FROM RESIDENTIAL SURFACE USING TRANSFERABLE RESIDUE SAMPLING TECHNIQUES AND VIDEO-FLUORESCENT IMAGING

    EPA Science Inventory

    The recent change from organophosphate (OP) to pyrethroid insecticides for indoor residential pest control may significantly affect the relative importance of different exposure routes because of differences in physical/chemical properties of these two classes of compounds. In...

  3. Levels of metabolites of organophosphate pesticides, phthalates, and bisphenol A in pooled urine specimens from pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa)

    PubMed Central

    Ye, Xibiao; Pierik, Frank H.; Angerer, Jürgen; Meltzer, Helle Margrete; Jaddoe, Vincent W.V.; Tiemeier, Henning; Hoppin, Jane A.; Longnecker, Matthew P.

    2013-01-01

    Concerns about reproductive and developmental health risks of exposure to organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6-trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were measured in 10 pooled urine samples representing 110 pregnant women who participated in the Norwegian Mother and Child Birth Cohort (MoBa) study in 2004. Daily intakes were estimated from urinary data and compared with reference doses (RfDs) and daily tolerable intakes (TDIs). The MoBa women had a higher mean BPA concentration (4.50 μg/L) than the pregnant women in the Generation R Study (Generation R) in the Netherlands and the National Health and Nutrition Examination Survey (NHANES) in the United States. The mean concentration of total DAP metabolites (24.20 μg/L) in MoBa women was higher than that in NHANES women but lower than that in Generation R women. The diethyl phthalate metabolite mono-ethyl phthalate (MEP) was the dominant phthalate metabolite in all three studies, with the mean concentrations of greater than 300 μg/L. The MoBa and Generation R women had higher mean concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) than the NHANES women. The estimated average daily intakes of BPA, chlorpyrifos/chlorpyrfios-methyl and phthalates in MoBa (and the other two studies) were below the RfDs and TDIs. The higher levels of metabolites in the MoBa participants may have been from intake via pesticide residues in food (organophosphates), consumption of canned food, especially fish/seafood (BPA), and use of personal care products (selected phthalates). PMID:19394271

  4. Acaricidal efficacies of Lippia gracilis essential oil and its phytochemicals against organophosphate-resistant and susceptible strains of Rhipicephalus (Boophilus) microplus.

    PubMed

    Costa-Júnior, Livio M; Miller, Robert J; Alves, Péricles B; Blank, Arie F; Li, Andrew Y; Pérez de León, Adalberto A

    2016-09-15

    Plant-derived natural products can serve as an alternative to synthetic compounds for control of ticks of veterinary and medical importance. Lippia gracilis is an aromatic plant that produces essential oil with high content of carvacrol and thymol monoterpenes. These monoterpenes have high acaricidal activity against Rhipicephalus (Boophilus) microplus. However, there are no studies that show efficacy differences of essential oils between susceptible and organophosphate resistant strains of R. (B.) microplus. The aim of the present study was to compare acaricidal effects of essential oils extracted from two different genotypes of L. gracilis and the main monoterpenes on larvae of both susceptible and organophosphate resistant R. (B.) microplus larvae. The efficacy of the essential oil of two genotypes of L. gracilis (106 and 201) and their monoterpenes carvacrol and thymol was measured using the larval immersion test on coumaphos-resistant and susceptible strains of R. (B.) microplus. Lethal concentrations were calculated using GraphPad Prism 6.0. Chemical analysis was performed by GC-MS and FID. Thymol and carvacrol were observed to be major constituents in 106 and 201L. gracilis genotype essential oils, respectively. Essential oils of both genotypes were more effective against organophosphate-resistant tick strain than susceptible tick strain. Carvacrol was 3.2 times more toxic to organophosphate resistant strain than to susceptible strain. Thymol was equally toxic to resistant and susceptible tick strains. The significantly higher efficacy monoterpene carvacrol against resistant ticks may lead to development of new natural product acaricide formulations for use to control organophosphate resistant R. (B.) microplus populations. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Development of a sensitive, generic and easy to use organophosphate skin disclosure kit.

    PubMed

    Worek, Franz; Wosar, Andreas; Baumann, Madlen; Thiermann, Horst; Wille, Timo

    2017-10-05

    Various organophosphorus compounds (OP), primarily the nerve agent VX and other V-agents, are highly toxic to humans after skin exposure. Percutaneous exposure by such OP results in a delayed onset of toxic signs which enables the initiation of specific countermeasures if contamination is detected rapidly. Presently available mobile detection systems can hardly detect skin exposure by low volatile OP. In order to fill this gap an OP skin disclosure kit was developed which should fulfill different requirements, i.e. a high sensitivity, coverage of human toxic OP, easy handling, rapid results, small dimension and weight. The kit includes a cotton swab to sample skin, human AChE as target and chemicals for a color reaction based on the Ellman assay which is recorded by visual inspection. OP is dissolved from the sampler in a test tube filled with phosphate buffer (0.1M, pH 7.4) and incubated with lyophilized human AChE for 1min. The reaction with acetylthiocholine and 5,5'-dithio-bis-2-nitrobenzoic acid (1min) results in a rich yellow color in the absence of OP and in contrast, in transparent or pale yellow buffer in the presence of OP. At the recommended conditions, the limit of detection is 100ng VX and Russian VX and 50ng Chinese VX on plain surface and 200ng VX on rat skin. With activated pesticides, paraoxon and malaoxon, a concentration of ∼10μg can be detected on plain surface. The ready-to-use kit has a weight of 16g and a size of 10×12×1cm. In the end, this kit has the potential to fill a major gap and to enable timely detection of OP skin exposure and initiation of life-saving countermeasures. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Development of status epilepticus, sustained calcium elevations and neuronal injury in a rat survival model of lethal paraoxon intoxication

    PubMed Central

    Deshpande, Laxmikant S.; Carter, Dawn S.; Phillips, Kristin F.; Blair, Robert E.; DeLorenzo, Robert J.

    2014-01-01

    Paraoxon (POX) is an active metabolite of organophosphate (OP) pesticide parathion that has been weaponized and used against civilian populations. Exposure to POX produces high mortality. OP poisoning is often associated with chronic neurological disorders. In this study, we optimize a rat survival model of lethal POX exposures in order to mimic both acute and long-term effects of POX intoxication. Male Sprague-Dawley rats injected with POX (4 mg/kg, ice-cold PBS, s.c.) produced a rapid cholinergic crisis that evolved into status epilepticus (SE) and death within 6–8 min. The EEG profile for POX induced SE was characterized and showed clinical and electrographic seizures with 7–10 Hz spike activity. Treatment of 100% lethal POX intoxication with an optimized three drug regimen (atropine, 2 mg/kg, i.p., 2-PAM, 25 mg/kg, i.m. and diazepam, 5 mg/kg, i.p.) promptly stopped SE and reduced acute mortality to 12% and chronic mortality to 18%. This model is ideally suited to test effective countermeasures against lethal POX exposure. Animals that survived the POX SE manifested prolonged elevations in hippocampal [Ca2+]i (Ca2+ plateau) and significant multifocal neuronal injury. POX SE induced Ca2+ plateau had its origin in Ca2+ release from intracellular Ca2+ stores since inhibition of ryanodine/ IP3 receptor lowered elevated Ca2+ levels post SE. POX SE induced neuronal injury and alterations in Ca2+ dynamics may underlie some of the long term morbidity associated with OP toxicity. PMID:24785379

  7. Two-dimensional ion chromatography for the separation of ionic organophosphates generated in thermally decomposed lithium hexafluorophosphate-based lithium ion battery electrolytes.

    PubMed

    Kraft, Vadim; Grützke, Martin; Weber, Waldemar; Menzel, Jennifer; Wiemers-Meyer, Simon; Winter, Martin; Nowak, Sascha

    2015-08-28

    A two-dimensional ion chromatography (IC/IC) technique with heart-cutting mode for the separation of ionic organophosphates was developed. These analytes are generated during thermal degradation of three different commercially available Selectilyte™ lithium ion battery electrolytes. The composition of the investigated electrolytes is based on 1M lithium hexafluorophosphate (LiPF6) dissolved in ethylene carbonate/dimethyl carbonate (50:50wt%, LP30), ethylene carbonate/diethyl carbonate (50:50wt%, LP40) and ethylene carbonate/ethyl methyl carbonate (50:50wt%, LP50). The organophosphates were pre-separated from PF6(-) anion on the low capacity A Supp 4 column, which was eluted with a gradient step containing acetonitrile. The fraction containing analytes was retarded on a pre-concentration column and after that transferred to the high capacity columns, where the separation was performed isocratically. Different stationary phases and eluents were applied on the 2nd dimension for the investigation of retention times, whereas the highly promising results were obtained with a high capacitive A Supp 10 column. The organophosphates generated in LP30 and LP40 electrolytes could be separated by application of an aqueous NaOH eluent providing fast analysis time within 35min. For the separation of the organophosphates of LP50 electrolyte due to its complexity a NaOH eluent containing a mixture of methanol/H2O was necessary. In addition, the developed two dimensional IC method was hyphenated to an inductively coupled plasma mass spectrometer (ICP-MS) using aqueous NaOH without organic modifiers. This proof of principle measurement was carried out for future quantitative investigation regarding the concentration of the ionic organophosphates. Furthermore, the chemical stability of several ionic organophosphates in water and acetonitrile at room temperature over a period of 10h was investigated. In both solvents no decomposition of the investigated analytes was observed and

  8. A Fast Response Capability within NOAA/NOS/CO-OPS

    DTIC Science & Technology

    2007-01-01

    A Fast Response Capability within NOAA/NOS/CO-OPS P. B. Burke NOAA/National Ocean Service/CO-OPS 1305 East-West Hwy. Silver Spring, MD 20910...USA pat.burke@noaa.gov T. Graff NOAA/National Ocean Service/CO-OPS 1305 East-West Hwy. Silver Spring, MD 20910 USA tammy.graff@noaa.gov... flotation hull, an instrumentation tower mounted atop the hull and a current meter mount with a mooring attachment. The triangular tower housed two

  9. Overall and class-specific scores of pesticide residues from fruits and vegetables as a tool to rank intake of pesticide residues in United States: a validation study

    PubMed Central

    Hu, Yang; Chiu, Yu Han; Hauser, Russ; Chavarro, Jorge; Sun, Qi

    2016-01-01

    Pesticide residues in fruits and vegetables are among the primary sources of pesticide exposure through diet, but the lack of adequate measurements hinder the research on health effects of pesticide residues. Pesticide Residue Burden Score (PRBS) for estimating overall dietary pesticide intake, organochlorine pesticide score (OC-PRBS) and organophosphate pesticide score (OP-PRBS) for estimating organochlorine and organophosphate pesticides-specific intake, respectively, were derived using U.S. Department of Agriculture Pesticide Data Program data and National Health and Nutrition Examination Survey (NHANES) food frequency questionnaire data. We evaluated the performance of these scores by validating the scores against pesticide metabolites measured in urine or serum among 3,679 participants in NHANES using generalized linear regression. The PRBS was positively associated with a score summarizing the ranks of all pesticide metabolites in a linear fashion (p for linear trend <0.001). Furthermore, individuals in the top quintile of this score had urinary pesticide metabolite levels 13.0% (95% CI 8.3%-17.7%) higher than individuals in the lowest quintile. Similarly, we observed significant associations of the OC-PRBS and OP-PRBS with the levels of lipid-adjusted total serum organochlorine pesticides and urinary creatinine-adjusted organophosphate pesticides, respectively. The relative difference (RD) in average pesticide metabolite rank between extreme quintiles was 17.8% (95% CI: 11.1%-24.4%, p for trend <0.001) for the OP-PRBS, whereas the RD was marginally significant at 7.0% (95% CI: -0.5%-14.4%, p for trend 0.07) for the OC-PRBS. The PRBS and OP-PRBS had similar performance when they were derived from fruits and vegetables with high vs. low pesticide residues, respectively (p for trend <0.001 for all associations). The OP-PRBS was associated with all measured organophosphate pesticides, whereas the positive association between OC-PRBS and averaged measured

  10. Overall and class-specific scores of pesticide residues from fruits and vegetables as a tool to rank intake of pesticide residues in United States: A validation study.

    PubMed

    Hu, Yang; Chiu, Yu-Han; Hauser, Russ; Chavarro, Jorge; Sun, Qi

    2016-01-01

    Pesticide residues in fruits and vegetables are among the primary sources of pesticide exposure through diet, but the lack of adequate measurements hinder the research on health effects of pesticide residues. Pesticide Residue Burden Score (PRBS) for estimating overall dietary pesticide intake, organochlorine pesticide score (OC-PRBS) and organophosphate pesticide score (OP-PRBS) for estimating organochlorine and organophosphate pesticides-specific intake, respectively, were derived using U.S. Department of Agriculture Pesticide Data Program data and National Health and Nutrition Examination Survey (NHANES) food frequency questionnaire data. We evaluated the performance of these scores by validating the scores against pesticide metabolites measured in urine or serum among 3,679 participants in NHANES using generalized linear regression. The PRBS was positively associated with a score summarizing the ranks of all pesticide metabolites in a linear fashion (p for linear trend <0.001). Furthermore, individuals in the top quintile of this score had urinary pesticide metabolite levels 13.0% (95% CI 8.3%-17.7%) higher than individuals in the lowest quintile. Similarly, we observed significant associations of the OC-PRBS and OP-PRBS with the levels of lipid-adjusted total serum organochlorine pesticides and urinary creatinine-adjusted organophosphate pesticides, respectively. The relative difference (RD) in average pesticide metabolite rank between extreme quintiles was 17.8% (95% CI: 11.1%-24.4%, p for trend <0.001) for the OP-PRBS, whereas the RD was marginally significant at 7.0% (95% CI: -0.5%-14.4%, p for trend 0.07) for the OC-PRBS. The PRBS and OP-PRBS had similar performance when they were derived from fruits and vegetables with high vs. low pesticide residues, respectively (p for trend <0.001 for all associations). The OP-PRBS was associated with all measured organophosphate pesticides, whereas the positive association between OC-PRBS and averaged measured

  11. ORGANOPHOSPHORUS HYDROLASE-BASED AMPEROMETRIC SENSOR: MODULATION OF SENSITIVITY AND SUBSTRATE SELECTIVITY

    EPA Science Inventory

    The detection of organophosphate (OP) insecticides with nitrophenyl substituents is reported using an enzyme electrode composed of Organophosphorus Hydrolase (OPH) and albumin co-immobilized to a nylon net and attached to a carbon paste electrode. The mechanism for this biosen...

  12. AQUEOUS CHLORINATION OF CHLORPYRIFOS IN THE PRESENCE OF BROMIDE AND NATURAL ORGANIC MATTER

    EPA Science Inventory

    The rates and pathways for pesticide transformation under drinking water treatment conditions are known for only a few pesticides and only under limited conditions. For example, it is known that chlorine reacting with organophosphate (OP) pesticides that contain the thiophosphat...

  13. AQUEOUS CHLORINATION OF CHLORPYRIFOS IN THE PRESENCE OF BROMIDE AND NOM

    EPA Science Inventory

    The rates and pathways for pesticide transformation under drinking water treatment conditions are known for only a few pesticides and only under limited conditions. For example, it is known that chlorine reacting with organophosphate (OP) pesticides that contain the thiophosphate...

  14. Application of Boiler Op for combustion optimization at PEPCO

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maines, P.; Williams, S.; Levy, E.

    1997-09-01

    Title IV requires the reduction of NOx at all stations within the PEPCO system. To assist PEPCO plant personnel in achieving low heat rates while meeting NOx targets, Lehigh University`s Energy Research Center and PEPCO developed a new combustion optimization software package called Boiler Op. The Boiler Op code contains an expert system, neural networks and an optimization algorithm. The expert system guides the plant engineer through a series of parametric boiler tests, required for the development of a comprehensive boiler database. The data are then analyzed by the neural networks and optimization algorithm to provide results on the boilermore » control settings which result in the best possible heat rate at a target NOx level or produce minimum NOx. Boiler Op has been used at both Potomac River and Morgantown Stations to help PEPCO engineers optimize combustion. With the use of Boiler Op, Morgantown Station operates under low NOx restrictions and continues to achieve record heat rate values, similar to pre-retrofit conditions. Potomac River Station achieves the regulatory NOx limit through the use of Boiler Op recommended control settings and without NOx burners. Importantly, any software like Boiler Op cannot be used alone. Its application must be in concert with human intelligence to ensure unit safety, reliability and accurate data collection.« less

  15. Response of common grackles to dietary concentrations of four organophosphate pesticides

    USGS Publications Warehouse

    Grue, C.E.

    1982-01-01

    Behavioral and physiological responses of common grackles to dietary concentrations of dicrotophos, fenitrothion, fenthion, and methyl parathion suggest mortality was largely due to pesticide-induced anorexia. Mortality was dose related, though consumption of treated diets was reduced such that birds on different geometrically arranged concentrations of the same pesticide ingested about the same amount of toxicant. Grackles that died lost an average of 28 to 36% of their initial body weight; visible fat was absent and muscle tissue was reduced on the sternum. Mortality of birds exposed to dicrotophos increased between May and August, although chemical intake remained relatively constant, and was associated with a natural decrease in fat and flesh condition in response to increased ambient temperatures and post-nuptial molt. Food consumption in songbirds exposed to organophosphates may be reduced significantly up to 12 hr after exposure ceases because of an unknown effect of these chemicals on their feeding behavior, but not repellency. The results caution against using median lethal dietary concentrations for other than ranking chemicals based on their relative toxicity, particularly in establishing safe environmental levels, and suggest that anorexia and physiological condition may be important factors in mortality of wild birds exposed to organophosphates.

  16. The Cognitive Orientation to daily Occupational Performance (CO-OP): A scoping review: L'approche CO-OP (Cognitive Orientation to daily Occupational Performance) : examen de la portée.

    PubMed

    Scammell, Emma M; Bates, Stephanie V; Houldin, Adina; Polatajko, Helene J

    2016-10-01

    The Cognitive Orientation to daily Occupational Performance (CO-OP) approach-now trademarked as the CO-OPApproach-was introduced in the literature in 2001 as an intervention to improve real-world performance in children with developmental coordination disorder. CO-OP has since appeared in numerous publications and has seen adoption with various populations. No compilation of the CO-OP literature is available. The purpose of this scoping review was to examine the extent (number) and nature (features and characteristics) of the literature on CO-OP. Using the scoping review methodology outlined by Arksey and O'Malley, 10 online databases were searched for materials discussing CO-OP. Materials found were reviewed by two reviewers, independently. Articles were categorized according to identified study characteristics. In all, 94 documents were found, including 27 research articles examining application and adaptations of CO-OP with eight populations. In all cases, the approach was deemed useful; however, in many cases, adaptations to the CO-OP protocol were recommended. CO-OP has been applied with a number of populations. There is now sufficient research to warrant a systematic review of the research literature. © CAOT 2016.

  17. Application of the perineal ostomy in severe organophosphate poisoned patients after catharsis.

    PubMed

    Zhang, D-M; Xiao, Q

    2014-01-01

    To investigate the efficacy of the one-piece ostomy bags for severe organophosphate poisoned patients after catharsis. Sixty cases of severe organophosphate poisoned patients who were given rhubarb catharsis after thorough nasal lavage were divided into two groups. The observation group used the one-piece ostomy bags whilst the control group used the disposable changing mats. The perineal skin changes, average daily hours of care, and cost of care rates were compared between the two groups. The rates of perineal skin changes were lower in the observation group than the control group (p < 0.05). The average daily hours of nursing and the cost of care were lower in the observation group than in the control group (p < 0.05). The application of one-piece perineal paste ostomy bag in poisoned patients after the catharsis can prevent the risk of nursing by protecting and promoting the care quality, reducing the nursing workload and improving their work efficiency. It can enhance the nurses' self-esteem, reduce patients' expenses and provide an objective basis for assessing the treatments.

  18. 10 CFR Appendixes O-P to Part 50 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false [Reserved] O Appendixes O-P to Part 50 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF PRODUCTION AND UTILIZATION FACILITIES Appendixes O-P to Part 50 [Reserved] ...

  19. 10 CFR Appendixes O-P to Part 50 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false [Reserved] O Appendixes O-P to Part 50 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF PRODUCTION AND UTILIZATION FACILITIES Appendixes O-P to Part 50 [Reserved] ...

  20. 10 CFR Appendixes O-P to Part 50 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false [Reserved] O Appendixes O-P to Part 50 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF PRODUCTION AND UTILIZATION FACILITIES Appendixes O-P to Part 50 [Reserved] ...

  1. 10 CFR Appendixes O-P to Part 50 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false [Reserved] O Appendixes O-P to Part 50 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF PRODUCTION AND UTILIZATION FACILITIES Appendixes O-P to Part 50 [Reserved] ...

  2. Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review.

    PubMed

    Sharma, Rahul; Gupta, Bhanushree; Singh, Namrata; Acharya, J R; Musilek, Kamil; Kuca, Kamil; Ghosh, Kallol Kumar

    2015-01-01

    Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam) and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.

  3. COMPARISONS OF PESTICIDE LEVELS AND EXPOSURES IN NHEXAS ARIZONA AND ARIZONA-MEXICO BORDER POPULATIONS

    EPA Science Inventory

    The distributions of organophosphate (OP) insecticides chlorpyrifos and diazinon in exposure matrices such as indoor air, house dust, food, and water have been determined for 416 homes in the general Arizona population, and for 87 homes along the Arizona-Mexico border. The con...

  4. Analysis of organophosphate-Zn metalloporphyrin interactions via UV-vis spectroscopy and molecular modeling.

    PubMed

    Rompoti, A; Dalal, N; Athanasopoulos, D; Rutan, S; Helburn, R

    2015-01-25

    UV-vis absorption spectra of zinc tetraphenylporphine (ZnTPP) on interaction with six organophosphorus (OP) compounds in cyclohexane were compared using ab initio methods and the molecular and solvation ligand descriptors π(*), Vx, and σ. OPs with polarizable hydrocarbon substituents in the homologous series tri-ethyl, -pentyl, -octyl, and -phenyl phosphates and the toxicologically relevant methyl paraoxon (1a-e) each gave a red shift in the Soret band (λsor) of ZnTPP in the range of 8-10 nm. Sensitivity as ΔAsor-b/Δug OP for the spectral band of the ligand bound ZnTPP (λsor-b) decreased with increasing extent of alkyl and aromatic substitution. Calculated and combined energies for OP and ZnTPP examined as a function of distance (Å) between ligand and porphyrin center suggest increased steric crowding with increasing Vx, and aromatic content of the OP. Spectrally fitted K1:1 and ΔAsor-b/ug OP each vary exponentially with Vx/σ. Lack of a red shift in λsor-b where ZnTPP was titrated with the toxic diethyl chlorophosphate (1g) is consistent with a model in which the magnitude of ΔEsor is proportional to the donor capacity of the phosphoryl-O ligand. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Potential clinical application of surface electromyography as indicator of neuromuscular recovery during weaning tests after organophosphate poisoning

    PubMed Central

    Sánchez, Maria Bernarda Salazar; Valdivieso, Alher Mauricio Hernández; Villanueva, Miguel Ángel Mañanas; Salazar, Andrés Felipe Zuluaga

    2017-01-01

    This study aimed to explore the usefulness of measuring respiratory muscle activity in mechanically ventilated patients suffering from acute organophosphate poisoning, with a view towards providing complementary information to determine the best time to suspend ventilatory support. Surface electromyography in respiratory muscles (diaphragm, external intercostal and sternocleidomastoid muscles) was recorded in a young man affected by self-poisoning with an unknown amount of parathion to determine the muscle activity level during several weaning attempts from mechanical ventilation. The energy distribution of each surface electromyography signal frequency, the synchronization between machine and patient and between muscles, acetylcholinesterase enzyme activity, and work of breathing and rapid shallow breathing indices were calculated in each weaning attempt. The work of breathing and rapid shallow breathing indices were not correlated with the failure/success of the weaning attempt. The diaphragm gradually increased its engagement with ventilation, achieving a maximal response that correlated with successful weaning and maximal acetylcholinesterase enzyme activity; in contrast, the activity of accessory respiratory muscles showed an opposite trend. PMID:28977266

  6. Portable Analytical Systems for On-Site Diagnosis of Exposure to Pesticides and Nerve Agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Yuehe; Wang, Jun; Liu, Guodong

    In this chapter, we summarize recent work in our laboratory on the development of sensitive portable analytical systems for use in on-site detection of exposure to organophosphate (OP) pesticides and chemical nerve agents. These systems are based on various nanomaterials functioning as transducers; recognition agents or labels and various elelectrochemical/immunoassay techniques. The studied nanomaterials included functionalized carbon nanotubes (CNT), zirconia nanoparticles (NPs) and quantum dots (QDs). Three biomarkers e.g. the free OPs, metabolites of OPs and protein-OP adducts in biological matrices have been employed for biomonitoring of OP exposure with our developed system. It has been found that the nanomaterial-basedmore » portable analytical systems have high sensitivity for the detection of the biomarkers, which suggest that these technologies offer great promise for the rapid and on-site detection and evaluation of OP exposure.« less

  7. [Clinical effect of hemoperfusion combined with hemodialysis in treatment of severe organophosphate pesticide poisoning].

    PubMed

    Guo, Lei; Ye, Hua; Pan, Liwei; Sun, Laifang; Ying, Binyu

    2014-12-01

    To investigate the clinical effect of hemoperfusion combined with hemodialysis in the treatment of severe organophosphate pesticide poisoning. Ninety-eight patients with severe organophosphate pesticide poisoning who were admitted to the emergency department of our hospital from March 2005 to September 2013 were equally divided into control group and observation group according to treatment methods. The control group was given conventional emergency treatment, while the observation group was given hemoperfusion combined with hemodialysis and the conventional emergency treatment. The clinical outcomes and complications of two groups were compared. In the control group, 35 patients were cured and 14 patients died, so the cure rate was 71.4%. In the treatment group, 46 patients were cured and 3 patients died, so the cure rate was 93.9%. The treatment group had a significantly higher cure rate than the control group (χ² = 8.611, P < 0.05). And the treatment group had significantly shorter duration of coma (P < 0.01), mean length of hospital stay (P < 0.01), and time to recovery of cholinesterase activity (P < 0.01) and a significantly reduced dose of atropine than the control group (P < 0.01). The control group had significantly more cases of urinary retention than the treatment group (18 vs. 6, χ² = 4.991, P < 0.05). And the control group had more cases of intermediate syndrome, respiratory failure, delayed neurological damage, and rebound than the treatment group. Hemoperfusion combined hemodialysis has a good clinical effect and causes fewer complications in treating severe organophosphate pesticide poisoning, so it is worthy of clinical promotion.

  8. Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers.

    PubMed

    Janssen, Nicole A H; Strak, Maciej; Yang, Aileen; Hellack, Bryan; Kelly, Frank J; Kuhlbusch, Thomas A J; Harrison, Roy M; Brunekreef, Bert; Cassee, Flemming R; Steenhof, Maaike; Hoek, Gerard

    2015-01-01

    We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects. We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm and an urban background site. Each volunteer visited at least three sites. We conducted health measurements before exposure, 2 h after exposure and the next morning. We measured air pollution on site and characterised the OP of PM2.5 and PM10 using three a-cellular assays; dithiotreitol (OP(DTT)), electron spin resonance (OP(ESR)) and ascorbic acid depletion (OP(AA)). In single-pollutant models, all measures of OP were significantly associated with increases in fractional exhaled nitric oxide and increases in interleukin-6 in nasal lavage 2 h after exposure. These OP associations remained significant after adjustment for co-pollutants when only the four outdoor sites were included, but lost significance when measurements at the underground site were included. Other health end points including lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. We found significant associations between three a-cellular measures of OP of PM and markers of airway and nasal inflammation. However, consistency of these effects in two-pollutant models depended on how measurements at the underground site were considered. Lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Our study, therefore, provides limited support for a role of OP in predicting acute health effects of PM in healthy young adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Residual efficacy of four organophosphate insecticides on concrete and galvanized steel surfaces against three liposcelid psocid species (Psocoptera: Liposcelidae) infesting stored products.

    PubMed

    Collins, P J; Nayak, M K; Kopittke, R

    2000-08-01

    Four organophosphate insecticides, azamethiphos, fenitrothion, chlorpyrifos-methyl, and pirimiphos-methyl, were tested as surface treatments on concrete (porous surface) and galvanized steel (nonporous surface) panels (0.3 by 0.3 m) against adults of three Liposcelid psocid spp.--Liposcelis bostrychophila Badonnel, Liposcelis entomophila (Enderlein), and Liposcelis paeta Pearman. Residual efficacy of these chemicals was assessed at 30 +/- 1 degrees C, 70 +/- 2% RH, and a photoperiod of 12:12 (L:D) h from 1 d after treatment (0 wk) and thereafter at weeks 1, 2, 4, 6, and 8, and then every 4 wk up to week 40. Mortality was recorded at exposure periods of 6 h and then every 24 h until end-point was achieved. L. bostrychophila was the most susceptible species to the organophosphates tested, followed by L. paeta and L. entomophila. We conclude that for long-term protection, azamethiphos is the preferred organophosphate against L. bostrychophila (up to 36 wk on steel and 24 wk on concrete storage surfaces) and L. paeta infestations only on steel surface (up to 28 wk). None of the four organophosphates tested, however, would provide long-term protection against L. paeta on concrete surface and against L. entomophila infestations on either concrete or steel storage surfaces.

  10. Validation of Direct Analysis Real Time source/Time-of-Flight Mass Spectrometry for organophosphate quantitation on wafer surface.

    PubMed

    Hayeck, Nathalie; Ravier, Sylvain; Gemayel, Rachel; Gligorovski, Sasho; Poulet, Irène; Maalouly, Jacqueline; Wortham, Henri

    2015-11-01

    Microelectronic wafers are exposed to airborne molecular contamination (AMC) during the fabrication process of microelectronic components. The organophosphate compounds belonging to the dopant group are one of the most harmful groups. Once adsorbed on the wafer surface these compounds hardly desorb and could diffuse in the bulk of the wafer and invert the wafer from p-type to n-type. The presence of these compounds on wafer surface could have electrical effect on the microelectronic components. For these reasons, it is of importance to control the amount of these compounds on the surface of the wafer. As a result, a fast quantitative and qualitative analytical method, nondestructive for the wafers, is needed to be able to adjust the process and avoid the loss of an important quantity of processed wafers due to the contamination by organophosphate compounds. Here we developed and validated an analytical method for the determination of organic compounds adsorbed on the surface of microelectronic wafers using the Direct Analysis in Real Time-Time of Flight-Mass Spectrometry (DART-ToF-MS) system. Specifically, the developed methodology concerns the organophosphate group. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Exposure of aircraft maintenance technicians to organophosphates from hydraulic fluids and turbine oils: a pilot study.

    PubMed

    Schindler, Birgit Karin; Koslitz, Stephan; Weiss, Tobias; Broding, Horst Christoph; Brüning, Thomas; Bünger, Jürgen

    2014-01-01

    Hydraulic fluids and turbine oils contain organophosphates like tricresyl phosphate isomers, triphenyl phosphate and tributyl phosphate from very small up to high percentages. The aim of this pilot study was to determine if aircraft maintenance technicians are exposed to relevant amounts of organophosphates. Dialkyl and diaryl phosphate metabolites of seven organophosphates were quantified in pre- and post-shift spot urine samples of technicians (N=5) by GC-MS/MS after solid phase extraction and derivatization. Pre- and post shift values of tributyl phosphate metabolites (dibutyl phosphate (DBP): median pre-shift: 12.5 μg/L, post-shift: 23.5 μg/L) and triphenyl phosphate metabolites (diphenyl phosphate (DPP): median pre-shift: 2.9 μg/L, post-shift: 3.5 μg/L) were statistically higher than in a control group from the general population (median DBP: <0.25 μg/L, median DPP: 0.5 μg/L). No tricresyl phosphate metabolites were detected. The aircraft maintenance technicians were occupationally exposed to tributyl and triphenyl phosphate but not to tricresyl phosphate, tri-(2-chloroethyl)- and tri-(2-chloropropyl)-phosphate. Further studies are necessary to collect information on sources, routes of uptake and varying exposures during different work tasks, evaluate possible health effects and to set up appropriate protective measures. Copyright © 2013 Elsevier GmbH. All rights reserved.

  12. Linking Exposure Science to Current and Future Pesticide Risk Assessment: From Biomonitoring to PBPK Modeling to High Throughput Screens

    EPA Science Inventory

    Organophosphate (OP) and pyrethroid (PYR) pesticides are amongst the most widely used insecticides. While useful in their ability to control and remove insects from cattle, crops, and homes, they are inherently linked to varying degrees of toxicity as a result of their actions on...

  13. Using Learning Environments to Create Meaningful Work for Co-Op Students

    ERIC Educational Resources Information Center

    Nevison, Colleen; Drewery, David; Pretti, Judene; Cormier, Lauren

    2017-01-01

    For students in cooperative education (co-op) programs, meaningful work is a critical aspect of participation and a key component of program success. However, studies have not explored how meaningful work can be created for co-op students. The purpose of this study was to evaluate the relationship between co-op students' perceptions of a learning…

  14. Acute organophosphorus poisoning complicated by acute coronary syndrome.

    PubMed

    Pankaj, Madhu; Krishna, Kavita

    2014-07-01

    We report a case of 30 year old alcoholic male admitted with vomiting, drowsiness, limb weakness and fasciculations after alleged history of consumption of 30 ml of chlorpyriphos insecticide. He had low serum cholinesterase levels. With standard treatment for organophosphorus poisoning (OPP), he improved gradually until day 5, when he developed neck and limb weakness and respiratory distress. This intermediate syndrome was treated with oximes, atropine and artificial ventilation. During treatment, his ECG showed fresh changes of ST elevation. High CPK & CPK-MB levels, septal hypokinesia on 2D echo suggested acute coronary syndrome. Coronary angiography was postponed due to his bedridden and obtunded status. The patient finally recovered fully by day 15 and was discharged. Acute coronary syndrome is a rare occurrence in OP poisoning. The present case thus emphasises the need for careful electrocardiographic and enzymatic monitoring of all patients of organophosphorus poisoning to prevent potential cardiac complication which can prove fatal.

  15. Geometry and Op Art.

    ERIC Educational Resources Information Center

    Brewer, Evelyn J.

    1999-01-01

    Describes an activity in which students use computers and techniques from Op Art to learn various geometric concepts. Allows them to see the distinct connection between art and mathematics from a personal perspective. Reinforces writing, speaking, and drawing skills while creating slide shows related to the project. (ASK)

  16. Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schallreuter, Karin U.; Institute for Pigmentary Disorders in Association with EM Arndt University of Greifswald; University of Bradford

    The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10{sup -3}M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. {sup 45}Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H{sub 2}O{sub 2}-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m{sup 2} surfacemore » area with its calcium gradient in the 10{sup -3}M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue.« less

  17. Emissions of organophosphate and brominated flame retardants from selected consumer products and building materials

    NASA Astrophysics Data System (ADS)

    Kemmlein, Sabine; Hahn, Oliver; Jann, Oliver

    The emissions of selected flame retardants were measured in 1- and 0.02-m 3 emission test chambers and 0.001-m 3 emission test cells. Four product groups were of interest: insulating materials, assembly foam, upholstery/mattresses, and electronics equipment. The experiments were performed under constant environmental conditions (23°C, 50% RH) using a fixed sample surface area and controlled air flow rates. Tris (2-chloro-isopropyl)phosphate (TCPP) was observed to be one of the most commonly emitted organophosphate flame retardants in polyurethane foam applications. Depending on the sample type, area-specific emission rates (SER a) of TCPP varied between 20 ng m -2 h -1 and 140 μg m -2 h -1. The emissions from electronic devices were measured at 60°C to simulate operating conditions. Under these conditions, unit specific emission rates (SER u) of organophosphates were determined to be 10-85 ng unit -1 h -1. Increasing the temperature increased the emission of several flame retardants by up to a factor of 500. The results presented in this paper indicate that emissions of several brominated and organophosphate flame retardants are measurable. Polybrominated diphenylethers exhibited an SER a of between 0.2 and 6.6 ng m -2 h -1 and an SER u of between 0.6 and 14.2 ng unit -1 h -1. Because of sink effects, i.e., sorption to chamber components, the emission test chambers and cells used in this study have limited utility for substances low vapour pressures, especially the highly brominated compounds; hexabromocyclododecane had an SER a of between 0.1 and 29 ng m -2 h -1 and decabromodiphenylether was not detectable at all.

  18. Electing a candidate: a speculative history of the bacterial phylum OP10.

    PubMed

    Dunfield, Peter F; Tamas, Ivica; Lee, Kevin C; Morgan, Xochitl C; McDonald, Ian R; Stott, Matthew B

    2012-12-01

    In 1998, a cultivation-independent survey of the microbial community in Obsidian Pool, Yellowstone National Park, detected 12 new phyla within the Domain Bacteria. These were dubbed 'candidate divisions' OP1 to OP12. Since that time the OP10 candidate division has been commonly detected in various environments, usually as part of the rare biosphere, but occasionally as a predominant community component. Based on 16S rRNA gene phylogeny, OP10 comprises at least 12 class-level subdivisions. However, despite this broad ecological and evolutionary diversity, all OP10 bacteria have eluded cultivation until recently. In 2011, two reference species of OP10 were taxonomically validated, removing the phylum from its 'candidate' status. Construction of a highly resolved phylogeny based on 29 universally conserved genes verifies its standing as a unique bacterial phylum. In the following paper we summarize what is known and what is suspected about the newest described bacterial phylum, the Armatimonadetes. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  19. Individual variability in esterase activity and CYP1A levels in Chinook salmon (Oncorhynchus tshawytscha) exposed to esfenvalerate and chlorpyrifos

    PubMed Central

    Wheelock, Craig E.; Eder, Kai J.; Werner, Inge; Huang, Huazhang; Jones, Paul D.; Brammell, Benjamin F.; Elskus, Adria A.; Hammock, Bruce D.

    2006-01-01

    Acetylcholinesterase (AChE) activity has traditionally been monitored as a biomarker of organophosphate (OP) and/or carbamate exposure. However, AChE activity may not be the most sensitive endpoint for these agrochemicals, because OPs can cause adverse physiological effects at concentrations that do not affect AChE activity. Carboxylesterases are a related family of enzymes that have higher affinity than AChE for some OPs and carbamates and may be more sensitive indicators of environmental exposure to these pesticides. In this study, carboxylesterase and AChE activity, cytochrome P4501A (CYP1A) protein levels, and mortality were measured in individual juvenile Chinook salmon (Oncorhynchus tshawytscha) following exposure to an OP (chlorpyrifos) and a pyrethroid (esfenvalerate). As expected, high doses of chlorpyrifos and esfenvalerate were acutely toxic, with nominal concentrations (100 and 1 μg/l, respectively) causing 100% mortality within 96 h. Exposure to chlorpyrifos at a high dose (7.3 μg/l), but not a low dose (1.2 μg/l), significantly inhibited AChE activity in both brain and muscle tissue (85% and 92% inhibition, respectively), while esfenvalerate exposure had no effect. In contrast, liver carboxylesterase activity was significantly inhibited at both the low and high chlorpyrifos dose exposure (56% and 79% inhibition, respectively), while esfenvalerate exposure still had little effect. The inhibition of carboxylesterase activity at levels of chlorpyrifos that did not affect AChE activity suggests that some salmon carboxylesterase isozymes may be more sensitive than AChE to inhibition by OPs. CYP1A protein levels were ∼30% suppressed by chlorpyrifos exposure at the high dose, but esfenvalerate had no effect. Three teleost species, Chinook salmon, medaka (Oryzias latipes) and Sacramento splittail (Pogonichthys macrolepidotus), were examined for their ability to hydrolyze a series of pyrethroid surrogate substrates and in all cases hydrolysis activity was

  20. Individual variability in esterase activity and CYP1A levels in Chinook salmon (Oncorhynchus tshawytscha) exposed to esfenvalerate and chlorpyrifos

    USGS Publications Warehouse

    Wheelock, C.E.; Eder, K.J.; Werner, I.; Huang, H.; Jones, P.D.; Brammell, B.F.; Elskus, A.A.; Hammock, B.D.

    2005-01-01

    Acetylcholinesterase (AChE) activity has traditionally been monitored as a biomarker of organophosphate (OP) and/or carbamate exposure. However, AChE activity may not be the most sensitive endpoint for these agrochemicals, because OPs can cause adverse physiological effects at concentrations that do not affect AChE activity. Carboxylesterases are a related family of enzymes that have higher affinity than AChE for some OPs and carbamates and may be more sensitive indicators of environmental exposure to these pesticides. In this study, carboxylesterase and AChE activity, cytochrome P4501A (CYP1A) protein levels, and mortality were measured in individual juvenile Chinook salmon (Oncorhynchus tshawytscha) following exposure to an OP (chlorpyrifos) and a pyrethroid (esfenvalerate). As expected, high doses of chlorpyrifos and esfenvalerate were acutely toxic, with nominal concentrations (100 and 1 ??g/l, respectively) causing 100% mortality within 96 h. Exposure to chlorpyrifos at a high dose (7.3 ??g/l), but not a low dose (1.2 ??g/l), significantly inhibited AChE activity in both brain and muscle tissue (85% and 92% inhibition, respectively), while esfenvalerate exposure had no effect. In contrast, liver carboxylesterase activity was significantly inhibited at both the low and high chlorpyrifos dose exposure (56% and 79% inhibition, respectively), while esfenvalerate exposure still had little effect. The inhibition of carboxylesterase activity at levels of chlorpyrifos that did not affect AChE activity suggests that some salmon carboxylesterase isozymes may be more sensitive than AChE to inhibition by OPs. CYP1A protein levels were ???30% suppressed by chlorpyrifos exposure at the high dose, but esfenvalerate had no effect. Three teleost species, Chinook salmon, medaka (Oryzias latipes) and Sacramento splittail (Pogonichthys macrolepidotus), were examined for their ability to hydrolyze a series of pyrethroid surrogate substrates and in all cases hydrolysis activity was

  1. Prenatal Organophosphates Exposure Alternates the Cleavage Plane Orientation of Apical Neural Progenitor in Developing Neocortex

    PubMed Central

    Chen, Xiao-Ping; Chen, Wei-Feng; Wang, Da-Wei

    2014-01-01

    Prenatal organophosphate exposure elicits long-term brain cytoarchitecture and cognitive function impairments, but the mechanism underlying the onset and development of neural progenitors remain largely unclear. Using precise positioned brain slices, we observed an alternated cleavage plane bias that emerged in the mitotic neural progenitors of embryonal neocortex with diazinion (DZN) and chlorpyrifos (CPF) pretreatment. In comparison with the control, DZN and CPF treatment induced decrease of vertical orientation, increase of oblique orientation, and increase of horizontal orientation. That is, the cleavage plane orientation bias had been rotated from vertical to horizontal after DZN and CPF treatment. Meanwhile, general morphology and mitotic index of the progenitors were unchanged. Acephate (ACP), another common organophosphate, had no significant effects on the cleavage plane orientation, cell morphology and mitotic index. These results represent direct evidence for the toxicity mechanism in onset multiplication of neural progenitors. PMID:24740262

  2. DETOXIFICATION OF ORGANOPHOSPHATE PESTICIDES BY IMMOBILIZED ESCHERICHIA COLI EXPRESSING ORGANOPHOSPHORUS HYDROLASE ON CELL SURFACE. (R823663)

    EPA Science Inventory

    An improved whole-cell technology for detoxifying organophosphate nerve agents was recently developed based on genetically engineered Escherichia coli with organophosphorus hydrolase anchored on the surface. This article reports the immobilization of these novel biocatalys...

  3. ORGANOPHOSPHATE PESTICIDE DEGRADATION IN THE PRESENCE OF NATURALLY OCCURRING AQUATIC CONSTITUENTS UNDER DRINKING WATER TREATMENT CONDITIONS

    EPA Science Inventory

    Little work to date has solely investigated the kinetics and pathways of pesticide transformations under drinking water treatment conditions. Free chlorine has been found to react with s-triazine, carbamate, and organophosphate pesticides. However, these experimental conditions...

  4. Brominated and organophosphate flame retardants target different neurodevelopmental stages, characterized with embryonic neural stem cells and neuronotypic PC12 cells.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Stapleton, Heather M; Seidler, Frederic J

    2017-09-01

    In addition to their activity as endocrine disruptors, brominated and organophosphate flame retardants are suspected to be developmental neurotoxicants, although identifying their specific mechanisms for that activity has been elusive. In the current study, we evaluated the effects of several flame retardants on neurodifferentiation using two in vitro models that assess distinct "decision nodes" in neural cell development: embryonic rat neural stem cells (NSCs), which evaluate the origination of neurons and glia from precursors, and rat neuronotypic PC12 cells, which characterize a later stage where cells committed to a neuronal phenotype undergo neurite outgrowth and neurotransmitter specification. In NSCs, both brominated and organophosphate flame retardants diverted the phenotype in favor of glia and away from formation of neurons, leading to an increased glia/neuron ratio, a common hallmark of the in vivo effects of neurotoxicants. For this early decision node, the brominated flame retardants were far more potent than the organophosphates. In PC12 cells, the brominated flame retardants were far less effective, whereas tris (1,3-dichloro-2-propyl) phosphate, an organophosphate, was more effective. Thus, the two classes of flame retardants differentially impact the two distinct vulnerable periods of neurodifferentiation. Furthermore, the effects on neurodifferentiation were separable from outright cytotoxicity, an important requirement in establishing a specific effect of these agents on neural cell development. These results reinforce the likelihood that flame retardants act as developmental neurotoxicants via direct effects on neural cell differentiation, over and above other activities that can impact nervous system development, such as endocrine disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Organophosphate-Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

    DTIC Science & Technology

    2014-10-01

    between blood cholinesterase activity and neurobehavioral deficits (Rohlman et al., 2011). Finally, one additional argument against the premise that AChE...baseline scan (repeated exposure CPF group only). 2.4 Cholinesterase activity Cholinesterase activity was assessed in brain using the method of...Moser VC.2006. Behavioral toxicity of cholinesterase inhibitors. In: Gupta, RC., editor. Toxicology of Organophosphate and Carbamate Compounds

  6. CAN FLU-LIKE ILLNESS BE AN INDICATION OF RECENT ORGANOPHOSPHATE PESTICIDE EXPOSURE IN PRESCHOOL CHILDREN?

    EPA Science Inventory

    Can flu-like illness be an indication of recent organophosphate pesticide exposure in preschool children? P Mendola*, D Barr, D Walsh, S Hern, S Rhoney, L Needham, E Hilborn, M Gonzales, C Carty, G Robertson, J Creason (US EPA, ORD, NHEERL, Research Triangle Park, NC 27711)
    <...

  7. Determination of airborne trialkyl and triaryl organophosphates originating from hydraulic fluids by gas chromatography-mass spectrometry. Development of methodology for combined aerosol and vapor sampling.

    PubMed

    Solbu, K; Thorud, S; Hersson, M; Ovrebø, S; Ellingsen, D G; Lundanes, E; Molander, P

    2007-08-17

    Methodology for personal occupational exposure assessment of airborne trialkyl and triaryl organophosphates originating from hydraulic fluids by active combined aerosol and vapor sampling at 1.5L/min is presented. Determination of the organophosphates was performed by gas chromatography-mass spectrometry. Combinations of adsorbents (Anasorb 747, Anasorb CSC, Chromosorb 106, XAD-2 and silica gel) with an upstream cassette with glass fiber or PTFE filters and different desorption/extraction solvents (CS(2), CS(2)-dimethylformamide (50:1, v/v), toluene, dichloromethane, methyl-t-butyl ether and methanol) have been evaluated for optimized combined vapor and aerosol air sampling of the organophosphates tri-isobutyl, tri-n-butyl, triphenyl, tri-o-cresyl, tri-m-cresyl and tri-p-cresyl phosphates. The combination of Chromosorb 106 and 37 mm filter cassette with glass fiber filter and dichloromethane as desorption/extraction solvent was the best combination for mixed phase air sampling of the organophosphates originating from hydraulic fluids. The triaryl phosphates were recovered solely from the filter, while the trialkyl phosphates were recovered from both the filter and the adsorbent. The total sampling efficiency on the combined sampler was in the range 92-101% for the studied organophosphates based on spiking experiments followed by pulling air through the sampler. Recoveries after 28 days storage were 98-102% and 99-101% when stored at 5 and -20 degrees C, respectively. The methodology was further evaluated in an exposure chamber with generated oil aerosol atmospheres with both synthetic and mineral base oils with added organophosphates in various concentrations, yielding total sampling efficiencies in close comparison to the spiking experiments. The applicability of the method was demonstrated by exposure measurements in a mechanical workshop where system suitability tests are performed on different aircraft components in a test bench, displaying tricresyl phosphate

  8. Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Halbrook, R.S.; Shugart, L.R.; Watson, A.P.

    1992-09-01

    A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. Amore » framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.« less

  9. Is This Op-Amp Any Good?: Lab-Built Checker Removes All Doubt!

    ERIC Educational Resources Information Center

    Harman, Charles

    2007-01-01

    Electronics instructors and students find it very helpful to be able to check an operational amplifier at the proto-board stage. Most students lack the experience or knowledge that it takes to recognize whether an op-amp is operating normally or not. This article discusses a handy op-amp checker that allows one to check and/or test op-amps at the…

  10. The utility of a "trauma 1 OP" activation at a level 1 pediatric trauma center.

    PubMed

    Hunt, Madison M; Stevens, Austin M; Hansen, Kristine W; Fenton, Stephen J

    2017-02-01

    To expedite flow of injured children suspected to require operative intervention, a "trauma 1 OP" (T1OP) activation classification was created. The purpose of this study was to review this strategy at a level 1 pediatric trauma center. A retrospective review of T1OP activations between 2003 and 2015 was performed. Children suspected of requiring neurosurgical intervention were classified as trauma 1 OP neuro (T1OP(N)). Comparisons were made to trauma 1 (T1) patients who required emergent operative intervention, excluding orthopedic injuries. Overall, 461 T1OP activations occurred (72% T1OP(N)) compared to 129 T1 activations requiring emergent surgery. Demographics were not significantly different between groups, although T1OP patients were slightly younger and more often experienced falls or were victims of abuse. Compared to T1 activations, T1OP activations had a significantly higher mortality rate (21% vs. 7%, p<0.001). Repeat head imaging was more common in the T1OP(N) group compared to imaged children in the T1 group (20% vs. 37%, p=0.05). T1OP(N) patients more often went directly to the OR (45% vs. 33%, p=0.02) and did so in a significantly faster period of time (32min vs. 53min, p<0.001). Use of the T1OP activations appropriately triaged surgical patients, resulting in significantly faster transport times to the OR. II, prognosis study. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Activity of Organophosphate Acid Anhydrase in Rangia cuneata.

    DTIC Science & Technology

    1988-01-01

    NO p UNCLASSIFIED N A CHESTER ET AL JAN 80 CRDEC-TR-9945 F/G 6/1 NL Emmns hhh K.."’ III - L *I -. Am-lii~~ -W , w w w V 00~~~S -DVLO M N S. d 00...ENG114EERIING% ~’CEN4TER CRDEC-TR-88045 ACTIVITY OF ORGANOPHOSPHATE ACID % im’. d l . ANHYDRASE IN RANGIA CUNEATA by Nancy A. Chester Wayne G. Landis, Ph.D...t iv ity. Results indicate three, groups if 1101eCul,1 C ei ghlt-eS t inaltes for S U I) t r’riL- sp ef i ti l , e n zym es w i thu n R. cunleata. When

  12. Organophosphorus poisoning (acute).

    PubMed

    Blain, Peter G

    2011-05-17

    Acetylcholinesterase inhibition by organophosphorus pesticides or organophosphate nerve agents can cause acute parasympathetic system dysfunction, muscle weakness, seizures, coma, and respiratory failure. Prognosis depends on the dose and relative toxicity of the specific compound, as well as pharmacokinetic factors. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute organophosphorus poisoning? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: activated charcoal (single or multiple doses), alpha(2) adrenergic receptor agonists, atropine, benzodiazepines, butyrylcholinesterase replacement therapy, cathartics, extracorporeal clearance, gastric lavage, glycopyrronium bromide (glycopyrrolate), ipecacuanha (ipecac), magnesium sulphate, milk or other home remedy immediately after ingestion, N-methyl-D-aspartate receptor antagonists, organophosphorus hydrolases, oximes, removing contaminated clothes and washing the poisoned person, and sodium bicarbonate.

  13. Status of the Signals of Opportunity Airborne Demonstrator (SoOp-AD)

    NASA Technical Reports Server (NTRS)

    Garrison, Jim; Lin, Yao-Cheng; Piepmeier, Jeff; Knuble, Joe; Hersey, Ken; Du Toit, Cornelus; Joseph, Alicia; Deshpande, Manohar; Alikakos, George; O'Brien, Steve; hide

    2016-01-01

    Root zone soil moisture (RZSM) is not directly measured by any current satellite instrument, despite its importance as a key link between surface hydrology and deeper processes. Presently, model assimilation of surface measurements or indirect estimates using other methods must be used to estimate this value. Signals of Opportunity (SoOp) methods, exploiting reflected P- and S-band communication satellite signals, have many of the benefits of both active and passive microwave remote sensing. Reutilization of active transmitters, with forward-scattering geometry, presents a strong reflected signal even at orbital altitudes. Microwave radiometry is advantageous as it measures emissivity, which is directly related to dielectric constant and sensitive to water content of soil. Synthetic aperture radar (SAR) is used in P-band (400 MHz) for soil moisture and biomass, but faces issues in obtaining permission to transmit due to spectrum regulations, particularly over North America and Europe. A primary advantage of SAR is excellent spatial resolution. Signals-of-opportunity (SoOp) reflectometry provides a good compromise between radiometry and SAR by providing decent sensitivity and special resolution for RZSM measurements without issues of spectrum access. Further, a SoOp instrument would not be limited to operating in only a few protected frequencies and is also expected to have less susceptibility to radio-frequency interference (RFI). Although advantageous if available, SoOp techniques do not require the ability to demodulate or decode the communication signals. The SoOp instrument is receive only and therefore requires much less electrical power than a SAR and is more similar to a radiometer in receiver architecture. These unique features of SoOp circumvent past obstacles to a spaceborne P-band remote sensing mission and have the potential to enable new RZSM measurements that are not possible with present technology. We will present the latest development status of a

  14. Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif.

    PubMed

    Hernández-Sánchez, Itzell E; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P; Jiménez-Bremont, Juan F

    2015-01-01

    The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization.

  15. Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif

    PubMed Central

    Hernández-Sánchez, Itzell E.; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P.; Jiménez-Bremont, Juan F.

    2015-01-01

    The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization. PMID:26442018

  16. Effects of a stable prostacyclin analog on experimental ischemic acute renal failure.

    PubMed Central

    Tobimatsu, M; Ueda, Y; Saito, S; Tsumagari, T; Konomi, K

    1988-01-01

    The effect of OP-41483, a stable prostacyclin (PGI2) analog, on ischemic acute renal failure (ARF) was investigated in dogs. Administration of OP-41483 for three days after ischemia significantly increased renal cortical blood flow (RCBF) when compared with dogs treated with the saline vehicle. In the OP-41483-treated group, serum creatinine levels remained relatively low during postoperative days 1-3 and mean survival time was prolonged. Injection of a silicone rubber vascular casting compound (Microfil) revealed increased numbers of visible renal cortical glomeruli and microvessels compared to the saline vehicle group. Histologic sections showed only very limited tubular necrosis, whereas sections of kidneys treated with saline showed extensive tubular necrosis. In conclusion, this stable prostacyclin analog provided a significant degree of protection for the kidneys from ischemic injury and may be useful in a clinical setting. Images Figs. 3A-D. Figs. 4A-D. PMID:3291800

  17. Prenatal exposure to persistent organic pollutants and organophosphate pesticides, and markers of glucose metabolism at birth.

    PubMed

    Debost-Legrand, Anne; Warembourg, Charline; Massart, Catherine; Chevrier, Cécile; Bonvallot, Nathalie; Monfort, Christine; Rouget, Florence; Bonnet, Fabrice; Cordier, Sylvaine

    2016-04-01

    Experimental evidence suggests that developmental exposure to persistent organic pollutants (POP) and to some non persistent pesticides may disrupt metabolic regulation of glucose metabolism and insulin secretion, and thereby contribute to the current epidemic of obesity and metabolic disorders. Quasi-experimental situations of undernutrition in utero have provided some information. However, the evidence in humans concerning the role of the prenatal environment in these disorders is contradictory, and little is known about long-term outcomes, such as type 2 diabetes, of prenatal exposure. Our aim was to evaluate the effects of prenatal exposure to POP and organophosphate pesticides on fetal markers of glucose metabolism in a sample of newborns from the Pelagie mother-child cohort in Brittany (France). Dialkylphosphate (DAP) metabolites of organophosphate pesticides were measured in maternal urine collected at the beginning of pregnancy. Cord blood was assayed for polychlorinated biphenyl congener 153 (PCB153), p,p'-dichlorodiphenyl dichloroethene (DDE) and other POP. Insulin and adiponectin were determined in cord blood serum (n=268). A decrease in adiponectin and insulin levels was observed with increasing levels of DDE, but only in girls and not boys. Adiponectin levels were not related to the concentrations of other POP or DAP metabolites. Decreasing insulin levels were observed with increasing PCB153 concentrations. Insulin levels increased with DAP urinary levels. Additional adjustment for BMI z-score at birth modified some of these relations. Our observations bring support for a potential role of organophosphate pesticides and POP in alterations to glucose metabolism observable at birth. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Baseline susceptibility to pyrethroid and organophosphate insecticides in two old world sand fly species (diptera: psychodidae)

    USDA-ARS?s Scientific Manuscript database

    A study was conducted with support from the Department of Defense’s Deployed Warfighter Protection (DWFP) Program to evaluate the susceptibility of two old world sand fly species, Phlebotomus papatasi and P. duboscqi, to a number of commonly used pyrethroid and organophosphate insecticides. A simpl...

  19. O&P (Ova and Parasite) Test

    MedlinePlus

    ... ova and parasite exam may be done in conjunction with or following a GI pathogens panel that ... infections, an O&P may be used in conjunction with other tests, such as a gastrointestinal (GI) ...

  20. Expert systems built by the Expert: An evaluation of OPS5

    NASA Technical Reports Server (NTRS)

    Jackson, Robert

    1987-01-01

    Two expert systems were written in OPS5 by the expert, a Ph.D. astronomer with no prior experience in artificial intelligence or expert systems, without the use of a knowledge engineer. The first system was built from scratch and uses 146 rules to check for duplication of scientific information within a pool of prospective observations. The second system was grafted onto another expert system and uses 149 additional rules to estimate the spacecraft and ground resources consumed by a set of prospective observations. The small vocabulary, the IF this occurs THEN do that logical structure of OPS5, and the ability to follow program execution allowed the expert to design and implement these systems with only the data structures and rules of another OPS5 system as an example. The modularity of the rules in OPS5 allowed the second system to modify the rulebase of the system onto which it was grafted without changing the code or the operation of that system. These experiences show that experts are able to develop their own expert systems due to the ease of programming and code reusability in OPS5.

  1. AC coupled three op-amp biopotential amplifier with active DC suppression.

    PubMed

    Spinelli, E M; Mayosky, M A

    2000-12-01

    A three op-amps instrumentation amplifier (I.A) with active dc suppression is presented. dc suppression is achieved by means of a controlled floating source at the input stage, to compensate electrode and op-amps offset voltages. This isolated floating source is built around an optical-isolated device using a general-purpose optocoupler, working as a photovoltaic generator. The proposed circuit has many interesting characteristics regarding simplicity and cost, while preserving common mode rejection ratio (CMRR) and high input impedance characteristics of the classic three op-amps I.A. As an example, a biopotential amplifier with a gain of 80 dB, a lower cutoff frequency of 0.1 Hz, and a dc input range of +/- 8 mV was built and tested. Using general-purpose op-amps, a CMRR of 105 was achieved without trimmings.

  2. Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States

    PubMed Central

    2017-01-01

    During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes. PMID:28317001

  3. Microsomal biotransformation of chlorpyrifos, parathion and fenthion in rainbow trout (Oncorhynchus mykiss) and coho salmon (Oncorhynchus kisutch): mechanistic insights into interspecific differences in toxicity

    PubMed Central

    Lavado, Ramon

    2010-01-01

    Rainbow trout often serve as a surrogate species evaluating xenobiotic toxicity in cold-water species including other salmonids of the same genus, which are listed as threatened or endangered. Biotransformation tends to show species-specific patterns that influence susceptibility to xenobiotic toxicity, particularly organophoshpate insecticides (OPs). To evaluate the contribution of biotransformation in the mechanism of toxicity of three organophosphate (phosphorothionate) insecticides, chlorpyrifos, parathion and fenthion, microsomal bioactivation and detoxification pathways were measured in gills, liver and olfactory tissues in juvenile rainbow trout (Oncorhynchus mykiss) and compared to juvenile coho salmon (Oncorhynchus kisutch). Consistent with species differences in acute toxicity, significantly higher chlorpyrifos bioactivation was found in liver microsomes of rainbow trout (up to 2-fold) when compared with coho salmon. Although bioactivation to the oxon was observed, the catalytic efficiency towards chlorpyrifos dearylation (detoxification) was significantly higher in liver for both species (1.82 and 0.79 for trout and salmon, respectively) when compared to desulfuration (bioactivation). Bioactivation of parathion to paraoxon was significantly higher (up to 2.2-fold) than detoxification to p-nitrophenol in all tissues of both species with rates of conversion in rainbow trout, again significantly higher than coho salmon. Production of fenoxon and fenthion sulfoxides from fenthion was detected only in liver and gills of both species with activities in rainbow trout significantly higher than coho salmon. NADPH-Dependent hydrolysis of fenthion was observed in all tissues, and was the only activity detected in olfactory tissues. These results indicate rainbow trout are more sensitive than coho salmon to the acute toxicity of OP pesticides because trout have higher catalytic rates of oxon formation. Thus, rainbow trout may serve as a conservative surrogate

  4. Safety measures associated with the use of organophosphate insecticides in the Haitian malaria control programme*

    PubMed Central

    Warren, McWilson; Ruebush, Trenton K.; Hobbs, Jesse H.; Hippolyte, Robert; Miller, Steve

    1985-01-01

    A programme emphasizing intensive training, use of protective equipment and uniforms, daily supervision of safety measures at work, and weekly monitoring of blood cholinesterase levels by the tintometric method was instituted to prevent toxicity in Haitian malaria workers during spraying with the organophosphate insecticides fenitrothion and malathion. The programme functioned well, depressed cholinesterase activity (≤ 50% of normal) being detected rapidly prior to the development of serious symptoms. Evidence of fenitrothion overexposure appeared in spraymen early in the first spray cycle, and was associated with faulty protective clothing and a failure to observe strictly the recommended safety measures at work. After these deficiencies were corrected, insecticide application continued without serious incidents or interruption of the programme. No serious reduction of cholinesterase activity was seen in a more limited study of spraymen using malathion. It is strongly recommended that similar training and monitoring programmes should be instituted whenever organophosphate pesticides are used as residual sprays for malaria control. This is particularly important in areas where the more toxic compound, fenitrothion, is to be used. PMID:3874715

  5. Ionic liquids composed of phosphonium cations and organophosphate, carboxylate, and sulfonate as lubricant antiwear additives

    DOE PAGES

    Zhou, Yan; Dyck, Jeffrey; Graham, Todd; ...

    2014-10-20

    Oil-soluble phosphonium-based ionic liquids (ILs) have recently been reported as potential ashless lubricant additives. This study is to expand the IL chemistry envelope and to achieve fundamental correlations between the ion structures and ILs’ physiochemical and tribological properties. Here we present eight ILs containing two different phosphonium cations and seven different anions from three groups: organophosphate, carboxylate, and sulfonate. The oil solubility of ILs seems largely governed by the IL molecule size and structure complexity. When used as oil additives, the ranking of effectiveness in wear protection for the anions are: organophosphate > carboxylate > sulfonate. All selected ILs outperformedmore » a commercial ashless anti-wear additive. Surface characterization from the top and the cross-section revealed the nanostructures and compositions of the tribo-films formed by the ILs. Some fundamental insights were achieved: branched and long alkyls improve the IL’s oil solubility, anions of a phosphonium-phosphate IL contribute most phosphorus in the tribofilm, and carboxylate anions, though free of P, S, N, or halogen, can promote the formation of an anti-wear tribofilm.« less

  6. Flexible, Low-Cost Sensor Based on Electrolyte Gated Carbon Nanotube Field Effect Transistor for Organo-Phosphate Detection

    PubMed Central

    Bhatt, Vijay Deep; Joshi, Saumya; Becherer, Markus; Lugli, Paolo

    2017-01-01

    A flexible enzymatic acetylcholinesterase biosensor based on an electrolyte-gated carbon nanotube field effect transistor is demonstrated. The enzyme immobilization is done on a planar gold gate electrode using 3-mercapto propionic acid as the linker molecule. The sensor showed good sensing capability as a sensor for the neurotransmitter acetylcholine, with a sensitivity of 5.7 μA/decade, and demonstrated excellent specificity when tested against interfering analytes present in the body. As the flexible sensor is supposed to suffer mechanical deformations, the endurance of the sensor was measured by putting it under extensive mechanical stress. The enzymatic activity was inhibited by more than 70% when the phosphate-buffered saline (PBS) buffer was spiked with 5 mg/mL malathion (an organophosphate) solution. The biosensor was successfully challenged with tap water and strawberry juice, demonstrating its usefulness as an analytical tool for organophosphate detection. PMID:28524071

  7. Comparative toxicities of organophosphate and pyrethroid insecticides to aquatic macroarthropods.

    PubMed

    Halstead, Neal T; Civitello, David J; Rohr, Jason R

    2015-09-01

    As agricultural expansion and intensification increase to meet the growing global food demand, so too will insecticide use and thus the risk of non-target effects. Insecticide pollution poses a particular threat to aquatic macroarthropods, which play important functional roles in freshwater ecosystems. Thus, understanding the relative toxicities of insecticides to non-target functional groups is critical for predicting effects on ecosystem functions. We exposed two common macroarthropod predators, the crayfish Procambarus alleni and the water bug Belostoma flumineum, to three insecticides in each of two insecticide classes (three organophosphates: chlorpyrifos, malathion, and terbufos; and three pyrethroids: esfenvalerate, λ-cyhalothrin, and permethrin) to assess their toxicities. We generated 150 simulated environmental exposures using the US EPA Surface Water Contamination Calculator to determine the proportion of estimated peak environmental concentrations (EECs) that exceeded the US EPA level of concern (0.5×LC50) for non-endangered aquatic invertebrates. Organophosphate insecticides generated consistently low-risk exposure scenarios (EECs<0.5×LC50) for both P. alleni and B. flumineum. Pyrethroid exposure scenarios presented consistently high risk (EECs>0.5×LC50) to P. alleni, but not to B. flumineum, where only λ-cyhalothrin produced consistently high-risk exposures. Survival analyses demonstrated that insecticide class accounted for 55.7% and 91.1% of explained variance in P. alleni and B. flumineum survival, respectively. Thus, risk to non-target organisms is well predicted by pesticide class. Identifying insecticides that pose low risk to aquatic macroarthropods might help meet increased demands for food while mitigating against potential negative effects on ecosystem functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Acetylcholinesterases of blood-feeding flies and ticks.

    PubMed

    Temeyer, Kevin B; Tuckow, Alexander P; Brake, Danett K; Li, Andrew Y; Pérez de León, Adalberto A

    2013-03-25

    Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer's disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, including biting flies and ticks. However, resistance to OPs in pests affecting animal and human health has compromised control efficacy. OP resistance often results from mutations producing an OP-insensitive AChE. Our studies have demonstrated production of OP-insensitive AChEs in biting flies and ticks. Complementary DNA (cDNA) sequences encoding AChEs were obtained for the horn fly, stable fly, sand fly, and the southern cattle tick. The availability of cDNA sequences enables the identification of mutations, expression and characterization of recombinant proteins, gene silencing for functional studies, as well as in vitro screening of novel inhibitors. The southern cattle tick expresses at least three different genes encoding AChE in their synganglion, i.e. brain. Gene amplification for each of the three known cattle tick AChE genes and expression of multiple alleles for each gene may reduce fitness cost associated with OP-resistance. AChE hydrolyzes the neurotransmitter, acetylcholine, but may have additional roles in physiology and development. The three cattle tick AChEs possess significantly different biochemical properties, and are expressed in neural and non-neural tissues, which suggest separation of structure and function. The remarkable complexity of AChEs in ticks suggested by combining genomic data from Ixodes scapularis with our genetic and biochemical data from Rhipicephalus microplus is suggestive of previously unknown gene duplication and diversification. Comparative studies between invertebrate and vertebrate AChEs could enhance our understanding of structure-activity relationships. Research with ticks as a model system offers the opportunity to

  9. Demodulation RFI statistics for a 3-stage op amp LED circuit

    NASA Astrophysics Data System (ADS)

    Whalen, James J.

    An experiment has been performed to demonstrate the feasibility of combining several methods of electromagnetic-compatibility analysis. The part of the experiment that demonstrates how RF signals cause interference in an audio-frequency (AF) circuit and how the interference can be suppressed is described. The circuit includes three operational amplifiers (op amps) and a light-emitting diode (LED). A 50 percent amplitude-modulated (AM) radio-frequency-interference (RFI) signal is used, varied over the range from 0.1 to 400 MHz. The AM frequency is 1 kHz. The RFI is injected into the inverting input of the first op amp, and the 1-kHz demodulation response of the amplifier is amplified by the second and third op amps and lights the LED to provide a visual display of the existence of RFI. An RFI suppression capacitor was added to reduce the RFI. The demodulation RFI results are presented as scatter plots for 35 741 op amps. Mean values and standard deviations are also shown.

  10. Organophosphate inhibition of avian salt gland Na, K-ATPase activity

    USGS Publications Warehouse

    Eastin, W.C.; Fleming, W.J.; Murray, H.C.

    1982-01-01

    1. Adult black ducks (Anas rubripes) were given freshwater or saltwater (1.5% NaCl) for 11 days and half of each group was also given an organophosphate (17 p.p.m. fenthion) in the diet on days 6–11.2. After 11 days, ducks drinking saltrwater had lost more weight and had higher plasma Na and uric acid concentration and osmolalities than birds drinking freshwater.3. Saltwater treatment stimulated the salt gland to increased weight and Na, K-ATPase activity.4. Fenthion generally reduced plasma and brain cholinesterase activity and depressed cholinesterase and Na, K-ATPase activities in salt glands of birds drinking saltwater.

  11. Pesticide residues variability and acute dietary risk assessment: a consumer perspective.

    PubMed

    Lefferts, L Y

    2000-07-01

    In relation to residue variability and acute dietary intake, this paper considers whether or not consumers are adequately protected, and makes recommendations for governments and international bodies. Existing risk assessment science is inadequate to lay to rest some concerns raised by the scientific community, and it is plausible that acute exposures to pesticides from the most contaminated food may be causing adverse effects in some consumers. Consumers International recommends that: (1) analysis and regulation of pesticides with a common mechanism of action (e.g. organophosphate insecticides) be conducted in an integrated, aggregated manner, not on a single pesticide basis; (2) exposure to pesticides in foods consumed in large amounts by children be reduced by revising good agricultural practices; (3) clear risk assessment policies for acute risk assessments be established at the national and international level; and (4) an additional safety factor be applied in order to protect children when establishing maximum residue limits (MRLs) for pesticides in the absence of reliable data on the effects of pesticides on children (e.g. no pesticide-specific tests on immature animals for effects on the developing brain, endocrine, or immune systems).

  12. Op art and visual perception.

    PubMed

    Wade, N J

    1978-01-01

    An attempt is made to list the visual phenomena exploited in op art. These include moire frinlude moiré fringes, afterimages, Hermann grid effects, Gestalt grouping principles, blurring and movement due to astigmatic fluctuations in accommodation, scintillation and streaming possibly due to eye movements, and visual persistence. The historical origins of these phenomena are also noted.

  13. Therapeutic effects of OP-1 on metal wear particle induced osteoblasts injury in vitro

    PubMed Central

    Sun, Guojing; Chen, Jianmin; Yang, Shufeng; Parker, Thomas MN; Goodman, Gary MP; Hasama, Jack M; Zhao, Jianning

    2015-01-01

    Aseptic lossening is a main reason for the revision of total joint arthroplasty. Metal-wear particles induced deregulation of bone resorption or formation has been considered as the major process of aseptic lossening. Osteogenic protein-1 (OP-1) can be used to improve bone formation. However, such effect is not clearly understood after the metal-wear particles injury. Here, we investigated the molecular mechanisms by which OP-1 regulates the activity of bone formation and anti-inflammatory after injury. Results showed that OP-1 increased cell viability and bone formation ability of impaired osteoblast cells at 72 hours after being injured by cobalt particles. Pathway analyses revealed that both mRNA and protein levels of Smad1 and Smad5 were significantly increased upon the treatment of OP-1 in the cell injury model. Similarly, runt-related transcription factor 2 (Runx2) was also significantly upregulated in the OP-1 treated cells. Moreover, treatment with OP-1 inhibited the secretion of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-18 in cobalt impaired cells. Collectively, these results suggest that OP-1 could inhibit cobalt particles induced cell injury by activating Smad1, Smad5, and Runx2, and such procedure is accompanied by anti-inflammatory reaction. PMID:26885192

  14. Defined, serum/feeder-free conditions for expansion and drug screening of primary B-acute lymphoblastic leukemia.

    PubMed

    Jiang, Zhiwu; Wu, Di; Ye, Wei; Weng, Jianyu; Lai, Peilong; Shi, Pengcheng; Guo, Xutao; Huang, Guohua; Deng, Qiuhua; Tang, Yanlai; Zhao, Hongyu; Cui, Shuzhong; Lin, Simiao; Wang, Suna; Li, Baiheng; Wu, Qiting; Li, Yangqiu; Liu, Pentao; Pei, Duanqing; Du, Xin; Yao, Yao; Li, Peng

    2017-12-05

    Functional screening for compounds represents a major hurdle in the development of rational therapeutics for B-acute lymphoblastic leukemia (B-ALL). In addition, using cell lines as valid models for evaluating responses to novel drug therapies raises serious concerns, as cell lines are prone to genotypic/phenotypic drift and loss of heterogeneity in vitro . Here, we reported that OP9 cells, not OP9-derived adipocytes (OP9TA), support the growth of primary B-ALL cells in vitro . To identify the factors from OP9 cells that support the growth of primary B-ALL cells, we performed RNA-Seq to analyze the gene expression profiles of OP9 and OP9TA cells. We thus developed a defined, serum/feeder-free condition (FI76V) that can support the expansion of a range of clinically distinct primary B-ALL cells that still maintain their leukemia-initiating ability. We demonstrated the suitability of high-throughput drug screening based on our B-ALL cultured conditions. Upon screening 378 kinase inhibitors, we identified a cluster of 17 kinase inhibitors that can efficiently kill B-ALL cells in vitro . Importantly, we demonstrated the synergistic cytotoxicity of dinaciclib/BTG226 to B-ALL cells. Taken together, we developed a defined condition for the ex vivo expansion of primary B-ALL cells that is suitable for high-throughput screening of novel compounds.

  15. Reducing the incidence of acute pesticide poisoning by educating farmers on integrated pest management in South India.

    PubMed

    Mancini, Francesca; Jiggins, Janice L S; O'Malley, Michael

    2009-01-01

    Sixty-five farmers reported on pesticide use and the signs and symptoms of acute pesticide poisoning when using two different plant protection strategies: in 2003 using chemical controls and in 2004 using an approach to Integrated Pest Management (IPM) based on an ecological analysis of the field conditions. Exposure to organophosphates was confirmed as a serious risk factor for occupational poisoning. The adoption of IPM reduced the use of pesticides and halved the incidence of acute pesticide poisoning. Overall, the pesticide use spectrum shifted towards lower WHO Hazard Classes. A reduction of adverse health effects was attained through a reduction in exposure to toxic pesticides and behavioural changes. Given that other strategies to reduce the rate of acute poisoning have proven ineffective, interventions aiming to minimize pesticide poisoning in India and in other developing countries with similar rural conditions should focus on restricting the use of highly toxic compounds and educating farmers on IPM.

  16. Carbon Dioxide Observational Platform System (CO-OPS), feasibility study

    NASA Technical Reports Server (NTRS)

    Bouquet, D. L.; Hall, D. W.; Mcelveen, R. P.

    1987-01-01

    The Carbon Dioxide Observational Platform System (CO-OPS) is a near-space, geostationary, multi-user, unmanned microwave powered monitoring platform system. This systems engineering feasibility study addressed identified existing requirements such as: carbon dioxide observational data requirements, communications requirements, and eye-in-the-sky requirements of other groups like the Defense Department, the Forestry Service, and the Coast Guard. In addition, potential applications in: earth system science, space system sciences, and test and verification (satellite sensors and data management techniques) were considered. The eleven month effort is summarized. Past work and methods of gathering the required observational data were assessed and rough-order-of magnitude cost estimates have shown the CO-OPS system to be most cost effective (less than $30 million within a 10 year lifetime). It was also concluded that there are no technical, schedule, or obstacles that would prevent achieving the objectives of the total 5-year CO-OPS program.

  17. Validation of the OpCost logging cost model using contractor surveys

    Treesearch

    Conor K. Bell; Robert F. Keefe; Jeremy S. Fried

    2017-01-01

    OpCost is a harvest and fuel treatment operations cost model developed to function as both a standalone tool and an integrated component of the Bioregional Inventory Originated Simulation Under Management (BioSum) analytical framework for landscape-level analysis of forest management alternatives. OpCost is an updated implementation of the Fuel Reduction Cost Simulator...

  18. Metabolism, Seizures, and Blood Flow in Brain Following Organophosphate Exposure: Mechanisms of Action and Possible Therapeutic Agents

    DTIC Science & Technology

    1991-01-31

    oxotremorine and arecoline have established the involvement of a cholinergic muscarinic mechanism in OP-induced seizure, but not in OP-induced vasodilation. To...brain transport ofI glc, Ch, leu, and gly, additional influx measurements were made following expssure to carbachol, arecoline, oxotremorine , and AF64a...such as oxotremorine (53, 54). Although the primary effect of OPs on brain ACh levels is well established, their additional primary and secondary

  19. An investigation of potential applications of OP-SAPS: Operational sampled analog processors

    NASA Technical Reports Server (NTRS)

    Parrish, E. A.; Mcvey, E. S.

    1976-01-01

    The impact of charge-coupled device (CCD) processors on future instrumentation was investigated. The CCD devices studied process sampled analog data and are referred to as OP-SAPS - operational sampled analog processors. Preliminary studies into various architectural configurations for systems composed of OP-SAPS show that they have potential in such diverse applications as pattern recognition and automatic control. It appears probable that OP-SAPS may be used to construct computing structures which can serve as special peripherals to large-scale computer complexes used in real time flight simulation. The research was limited to the following benchmark programs: (1) face recognition, (2) voice command and control, (3) terrain classification, and (4) terrain identification. A small amount of effort was spent on examining a method by which OP-SAPS may be used to decrease the limiting ground sampling distance encountered in remote sensing from satellites.

  20. DEVELOPMENTAL NEUROTOXICITY OF ORGANOPHOSPHATES TARGETS CELL CYCLE AND APOPTOSIS, REVEALED BY TRANSCRIPTIONAL PROFILES IN VIVO AND IN VITRO

    PubMed Central

    Slotkin, Theodore A.; Seidler, Frederic J.

    2012-01-01

    Developmental organophosphate exposure reduces the numbers of neural cells, contributing to neurobehavioral deficits. We administered chlorpyrifos or diazinon to newborn rats on postnatal days 1–4, in doses straddling the threshold for barely-detectable cholinesterase, and evaluated gene expression in the cell cycle and apoptosis pathways on postnatal day 5. Both organophosphates evoked transcriptional changes in 20–25% of the genes in each category; chlorpyrifos and diazinon targeted the same genes, with similar magnitudes of change, as evidenced by high concordance. Furthermore, the same effects were obtained with doses above or below the threshold for cholinesterase inhibition, indicating a mechanism unrelated to anticholinesterase actions. We then evaluated the effects of chlorpyrifos in undifferentiated and differentiating PC12 cells and found even greater targeting of cell cycle and apoptosis genes, affecting up to 40% of all genes in the pathways. Notably, the genes affected in undifferentiated cells were not concordant with those in differentiating cells, pointing to dissimilar outcomes dependent on developmental stage. The in vitro model successfully identified 60–70% of the genes affected by chlorpyrifos in vivo, indicating that the effects are exerted directly on developing neural cells. Our results show that organophosphates target the genes regulating the cell cycle and apoptosis in the developing brain and in neuronotypic cells in culture, with the pattern of vulnerability dependent on the specific stage of development. Equally important, these effects do not reflect actions on cholinesterase and operate at exposures below the threshold for any detectable inhibition of this enzyme. PMID:22222554

  1. Developmental neurotoxicity of organophosphates targets cell cycle and apoptosis, revealed by transcriptional profiles in vivo and in vitro.

    PubMed

    Slotkin, Theodore A; Seidler, Frederic J

    2012-03-01

    Developmental organophosphate exposure reduces the numbers of neural cells, contributing to neurobehavioral deficits. We administered chlorpyrifos or diazinon to newborn rats on postnatal days 1-4, in doses straddling the threshold for barely-detectable cholinesterase inhibition, and evaluated gene expression in the cell cycle and apoptosis pathways on postnatal day 5. Both organophosphates evoked transcriptional changes in 20-25% of the genes in each category; chlorpyrifos and diazinon targeted the same genes, with similar magnitudes of change, as evidenced by high concordance. Furthermore, the same effects were obtained with doses above or below the threshold for cholinesterase inhibition, indicating a mechanism unrelated to anticholinesterase actions. We then evaluated the effects of chlorpyrifos in undifferentiated and differentiating PC12 cells and found even greater targeting of cell cycle and apoptosis genes, affecting up to 40% of all genes in the pathways. Notably, the genes affected in undifferentiated cells were not concordant with those in differentiating cells, pointing to dissimilar outcomes dependent on developmental stage. The in vitro model successfully identified 60-70% of the genes affected by chlorpyrifos in vivo, indicating that the effects are exerted directly on developing neural cells. Our results show that organophosphates target the genes regulating the cell cycle and apoptosis in the developing brain and in neuronotypic cells in culture, with the pattern of vulnerability dependent on the specific stage of development. Equally important, these effects do not reflect actions on cholinesterase and operate at exposures below the threshold for any detectable inhibition of this enzyme. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. A sensitive acetylcholinesterase biosensor based on gold nanorods modified electrode for detection of organophosphate pesticide.

    PubMed

    Lang, Qiaolin; Han, Lei; Hou, Chuantao; Wang, Fei; Liu, Aihua

    2016-08-15

    A sensitive amperometric acetylcholinesterase (AChE) biosensor, based on gold nanorods (AuNRs), was developed for the detection of organophosphate pesticide. Compared with Au@Ag heterogeneous NRs, AuNRs exhibited excellent electrocatalytic properties, which can electrocatalytically oxidize thiocholine, the hydrolysate of acetylthiocholine chloride (ATCl) by AChE at +0.55V (vs. SCE). The AChE/AuNRs/GCE biosensor was fabricated on basis of the inhibition of AChE activity by organophosphate pesticide. The biosensor could detect paraoxon in the linear range from 1nM to 5μM and dimethoate in the linear range from 5nM to 1μM, respectively. The detection limits of paraoxon and dimethoate were 0.7nM and 3.9nM, which were lower than the reported AChE biosensor. The proposed biosensor could restore to over 95% of its original current, which demonstrated the good reactivation. Moreover, the biosensor can be applicable to real water sample measurement. Thus, the biosensor exhibited low applied potential, high sensitivity and good stability, providing a promising tool for analysis of pesticides. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Solid-phase microextraction of organophosphate pesticides in source waters for drinking water treatment facilities.

    PubMed

    Flynt, Elizabeth; Dupuy, Aubry; Kennedy, Charles; Bennett, Shanda

    2006-09-01

    The rapid detection of contaminants in our nation's drinking water has become a top homeland security priority in this time of increased national vigilance. Real-time monitoring of drinking water for deliberate or accidental contamination is key to national security. One method that can be employed for the rapid screening of pollutants in water is solid-phase microextraction (SPME). SPME is a rapid, sensitive, solvent-free system that can be used to screen for contaminants that have been accidentally or intentionally introduced into a water system. A method using SPME has been developed and optimized for the detection of seven organophosphate pesticides in drinking water treatment facility source waters. The method is tested in source waters for drinking water treatment facilities in Mississippi and Alabama. Water is collected from a deepwater well at Stennis Space Center (SSC), MS, the drinking water source for SSC, and from the Converse Reservoir, the main drinking water supply for Mobile, AL. Also tested are samples of water collected from the Mobile Alabama Water and Sewer System drinking water treatment plant prior to chlorination. The method limits of detection for the seven organophosphates were comparable to those described in several Environmental Protection Agency standard methods. They range from 0.25 to 0.94 microg/L.

  4. TRANSCRIPTIONAL PROFILES FOR GLUTAMATE TRANSPORTERS REVEAL DIFFERENCES BETWEEN ORGANOPHOSPHATES BUT SIMILARITIES WITH UNRELATED NEUROTOXICANTS

    PubMed Central

    Slotkin, Theodore A.; Lobner, Doug; Seidler, Frederic J.

    2010-01-01

    The developmental neurotoxicity of organophosphates involves mechanisms other than their shared property as cholinesterase inhibitors, among which are excitotoxicity and oxidative stress. We used PC12 cells as a neurodevelopmental model to compare the effects of chlorpyrifos and diazinon on the expression of genes encoding glutamate transporters. Chlorpyrifos had a greater effect in cells undergoing nerve growth factor-induced neurodifferentiation as compared to undifferentiated PC12 cells, with peak sensitivity at the initiation of differentiation, reflecting a global upregulation of all the glutamate transporter genes expressed in this cell line. In differentiating cells, chlorpyrifos had a significantly greater effect than did diazinon and concordance analysis indicated no resemblance in their expression patterns. At the same time, the smaller effects of diazinon were highly concordant with those of an organochlorine pesticide (dieldrin) and a metal (divalent nickel). We also performed similar evaluations for the cystine/glutamate exchanger, which provides protection against oxidative stress by moving cystine into the cell; again, chlorpyrifos had the greatest effect, in this case reducing expression in undifferentiated and differentiating cells. Our results point to excitotoxicity and oxidative stress as major contributors to the noncholinesterase mechanisms that distinguish the neurodevelopmental outcomes betweem different organophosphates while providing a means whereby apparently unrelated neurotoxicants may produce similar outcomes. PMID:20600679

  5. Organophosphate insecticide poisoning of Canada geese in the Texas panhandle

    USGS Publications Warehouse

    White, D.H.; Mitchell, C.A.; Wynn, L.D.; Flickinger, Edward L.; Kolbe, E.J.

    1982-01-01

    Sixteen hundred waterfowl, mostly Canada Geese, died near Etter, Texas, in late January 1981 from anticholinesterase poisoning. Winter wheat in the area of the die-off had been treated with organophosphate insecticides to control greenbugs. Cholinesterase (ChE) levels in brains of a sample of geese found dead were 75% below normal, enough to account for death (Ludke et al. 1975). The gastrointestinal (G I) tracts of geese found dead were packed with winter wheat; gas chromatography techniques identified parathion and methyl parathion in the GI tract contents. Residues of both chemicals were confirmed by mass spectrometry. We recommend that less toxic materials, such as malathion, be used on grain crops when waterfowl are in the vicinity of treatment.

  6. Cellular Immune Response in Young Children Accounts for Recurrent Acute Otitis Media

    PubMed Central

    Sharma, Sharad K.; Pichichero, Michael E.

    2013-01-01

    Acute otitis media (AOM) is a common disease in young children. Streptococcus pneumoniae(Spn) and Haemophilus influenzae (NTHi) are the two most common pathogens that cause AOM. Over the past 5 years our group has been studying the immunologic profile of children that experience repeated AOM infections despite tympanocentesis drainage of middle ear fluid and individualized antibiotic treatment; we call these children stringently-defined otitis-prone (sOP). Although protection against AOM is primarily mediated by ototpathogen-specific antibody, our recent studies suggest that suboptimal memory B-& T- cell responses and an immaturity in antigen presenting cells may play a significant role in the propensity to recurrent AOM infections. This review focuses on the studies performed to define immunologic dysfunction in sOP children. PMID:24022464

  7. OpCost: an open-source system for estimating costs of stand-level forest operations

    Treesearch

    Conor K. Bell; Robert F. Keefe; Jeremy S. Fried

    2017-01-01

    This report describes and documents the OpCost forest operations cost model, a key component of the BioSum analysis framework. OpCost is available in two editions: as a callable module for use with BioSum, and in a stand-alone edition that can be run directly from R. OpCost model logic and assumptions for this open-source tool are explained, references to the...

  8. INDOOR AIR CONCENTRATIONS OF ORGANOCHLORINE, ORGANOPHOSPHATE AND PYRETHROID PESTICIDES IN THE US: FOUR STUDIES, SIX STATES AND TWENTY YEARS

    EPA Science Inventory

    Pesticides used to control indoor pests have transitioned across the chemicals classes of organochlorine, organophosphate, and pyrethroid compounds from the 1980's to the present. This work summarizes the pesticide concentrations measured from the indoor air of homes from four st...

  9. Downregulation of human paraoxonase 1 (PON1) by organophosphate pesticides in HepG2 cells.

    PubMed

    Medina-Díaz, Irma Martha; Ponce-Ruiz, Néstor; Ramírez-Chávez, Bryana; Rojas-García, Aurora Elizabeth; Barrón-Vivanco, Briscia S; Elizondo, Guillermo; Bernal-Hernández, Yael Y

    2017-02-01

    Paraoxonase 1 (PON1) is a calcium-dependent esterase synthesized primarily in the liver and secreted into the plasma where it is associated with high-density lipoproteins (HDL). PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs) such as methyl parathion and chlorpyrifos. Thus, PON1 activity and expression levels are important for determining susceptibility against OPs poisoning. Some studies have demonstrated that OPs can modulate gene expression through interactions with nuclear receptors. In this study, we evaluated the effects of methyl parathion and chlorpyrifos on the modulation of PON1 in Human Hepatocellular Carcinoma (HepG2) cells by real-time PCR, PON1 activity assay, and western blot. The results showed that the treatments with methyl parathion and chlorpyrifos decreased PON1 mRNA and immunoreactive protein and increased inflammatory cytokines in HepG2 cells. The effects of methyl parathion and chlorpyrifos on the downregulation of PON1 gene expression in HepG2 cells may provide evidence of OPs cytotoxicity related to oxidative stress and an inflammatory response. A decrease in the expression of the PON1 gene may increase the susceptibility to OPs intoxication and the risk of diseases related to inflammation and oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 490-500, 2017. © 2016 Wiley Periodicals, Inc.

  10. The MetOp second generation 3MI instrument

    NASA Astrophysics Data System (ADS)

    Manolis, Ilias; Grabarnik, Semen; Caron, Jérôme; Bézy, Jean-Loup; Loiselet, Marc; Betto, Maurizio; Barré, Hubert; Mason, Graeme; Meynart, Roland

    2013-10-01

    The MetOp-SG programme is a joint Programme of EUMETSAT and ESA. ESA develops the prototype MetOp-SG satellites (including associated instruments) and procures, on behalf of EUMETSAT, the recurrent satellites (and associated instruments). Two parallel, competitive phase A/B1 studies for MetOp Second Generation (MetOp-SG) have been concluded in May 2013. The implementation phases (B2/C/D/E) are planned to start the first quarter of 2014. ESA is responsible for instrument design of six missions, namely Microwave Sounding Mission (MWS), Scatterometer mission (SCA), Radio Occultation mission (RO), Microwave Imaging mission (MWI), Ice Cloud Imager (ICI) and Multi-viewing, Multi-channel, Multi-polarisation imaging mission (3MI). The paper will present the main performances of the 3MI instrument and will highlight the performance improvements with respect to its heritage derived by the POLDER instrument, such as number of spectral channels and spectral range coverage, swath and ground spatial resolution. The engineering of some key performance requirements (multi-viewing, polarisation sensitivity, straylight etc.) will also be discussed. The results of the feasibility studies will be presented together with the programmatics for the instrument development. Several pre-development activities have been initiated to retire highest risks and to demonstrate the ultimate performances of the 3MI optics. The scope, objectives and current status of those activities will be presented. Key technologies involved in the 3MI instrument design and implementation are considered to be: the optical design featuring aspheric optics, the implementation of broadband Anti Reflection coatings featuring low polarisation and low de-phasing properties, the development and qualification of polarisers with acceptable performances as well as spectral filters with good uniformities over a large clear aperture.

  11. Ultra-sensitive PSA Following Prostatectomy Reliably Identifies Patients Requiring Post-Op Radiotherapy

    PubMed Central

    Kang, Jung Julie; Reiter, Robert; Steinberg, Michael; King, Christopher R.

    2015-01-01

    PURPOSE Integrating ultra-sensitive PSA (uPSA) into surveillance of high-risk patients following radical prostatectomy (RP) potentially optimizes management by correctly identifying actual recurrences, promoting an early salvage strategy and minimizing overtreatment. The power of uPSA following surgery to identify eventual biochemical failures is tested. PATIENTS AND METHODS From 1991–2013, 247 high-risk patients with a median follow-up was 44 months after RP were identified (extraprostatic extension and/or positive margin). Surgical technique, initial PSA (iPSA), pathology and post-op PSA were analyzed. The uPSA assay threshold was 0.01 ng/mL. Conventional biochemical relapse (cBCR) was defined as PSA ≥0.2 ng/mL. Kaplan Meier and Cox multivariate analyses (MVA) compared uPSA recurrence vs. cBCR rates. RESULTS Sensitivity analysis identified uPSA ≥0.03 as the optimal threshold identifying recurrence. First post-op uPSA ≥0.03, Gleason grade, T-stage, iPSA, and margin status predicted cBCR. On MVA, only first post-op uPSA ≥0.03, Gleason grade, and T-stage independently predicted cBCR. First post-op uPSA ≥0.03 conferred the highest risk (HR 8.5, p<0.0001) and discerned cBCR with greater sensitivity than undetectable first conventional PSA (70% vs. 46%). Any post-op PSA ≥0.03 captured all failures missed by first post-op value (100% sensitivity) with accuracy (96% specificity). Defining failure at uPSA ≥0.03 yielded a median lead-time advantage of 18 months (mean 24 months) over the conventional PSA ≥0.2 definition. CONCLUSION uPSA ≥0.03 is an independent factor, identifies BCR more accurately than any traditional risk factors, and confers a significant lead-time advantage. uPSA enables critical decisions regarding timing and indication for post-op RT among high-risk patients following RP. PMID:25463990

  12. DSN G/T(sub op) and telecommunications system performance

    NASA Technical Reports Server (NTRS)

    Stelzried, C.; Clauss, R.; Rafferty, W.; Petty, S.

    1992-01-01

    Provided here is an intersystem comparison of present and evolving Deep Space Network (DSN) microwave receiving systems. Comparisons of the receiving systems are based on the widely used G/T sub op figure of merit, which is defined as antenna gain divided by operating system noise temperature. In 10 years, it is expected that the DSN 32 GHz microwave receiving system will improve the G/T sub op performance over the current 8.4 GHz system by 8.3 dB. To compare future telecommunications system end-to-end performance, both the receiving systems' G/T sub op and spacecraft transmit parameters are used. Improving the 32 GHz spacecraft transmitter system is shown to increase the end-to-end telecommunications system performance an additional 3.2 dB, for a net improvement of 11.5 dB. These values are without a planet in the field of view (FOV). A Saturn mission is used for an example calculation to indicate the degradation in performance with a planet in the field of view.

  13. Graphene oxide based sol-gel stainless steel fiber for the headspace solid-phase microextraction of organophosphate ester flame retardants in water samples.

    PubMed

    Jin, Tingting; Cheng, Jing; Cai, Cuicui; Cheng, Min; Wu, Shiju; Zhou, Hongbin

    2016-07-29

    In this paper, graphene oxide was coated onto a stainless steel wire through sol-gel technique and it was used as a solid phase microextraction (SPME) fiber. The prepared fiber was characterized by scanning electron microscopy (SEM), which displayed that the fiber had crinkled surface and porous structure The application of the fiber was evaluated through the headspace SPME of nine organophosphate ester flame retardants (OPFRs) with different characteristics in water samples followed by gas chromatography and nitrogen-phosphorous detector (GC/NPD). The major factors influencing the extraction efficiency, including the extraction and desorption conditions, were studied and optimized. Under the optimum conditions, the proposed method was evaluated, and applied to the analysis of organophosphate ester flame retardants in real environmental water samples. The results demonstrated the HS-SPME method based on GO sol-gel fiber had good linearity (R>0.9928), and limits of detection (1.4-135.6ngL(-1)), high repeatability (RSD<9.8%) and good recovery (76.4-112.4%). The GO based sol-gel fiber displayed bigger extraction capability than the commercial PDMS fiber and the pure sol-gel fiber for both polar and apolar organophosphate esters, especially for the OPFRs containing benzene rings. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Study on multiple-hops performance of MOOC sequences-based optical labels for OPS networks

    NASA Astrophysics Data System (ADS)

    Zhang, Chongfu; Qiu, Kun; Ma, Chunli

    2009-11-01

    In this paper, we utilize a new study method that is under independent case of multiple optical orthogonal codes to derive the probability function of MOOCS-OPS networks, discuss the performance characteristics for a variety of parameters, and compare some characteristics of the system employed by single optical orthogonal code or multiple optical orthogonal codes sequences-based optical labels. The performance of the system is also calculated, and our results verify that the method is effective. Additionally it is found that performance of MOOCS-OPS networks would, negatively, be worsened, compared with single optical orthogonal code-based optical label for optical packet switching (SOOC-OPS); however, MOOCS-OPS networks can greatly enlarge the scalability of optical packet switching networks.

  15. The MetOp second generation 3MI mission

    NASA Astrophysics Data System (ADS)

    Manolis, Ilias; Caron, Jérôme; Grabarnik, Semen; Bézy, Jean-Loup; Betto, Maurizio; Barré, Hubert; Mason, Graeme; Meynart, Roland

    2017-11-01

    ESA is currently running two parallel, competitive phase A/B1 studies for MetOp Second Generation (MetOp-SG). MetOp-SG is the space segment of EUMETSAT Polar System (EPS-SG) consisting of the satellites and instruments. The Phase A/B1 studies will be completed in the first quarter of 2013. The final implementation phases (B2/C/D) are planned to start 2013. ESA is responsible for instrument design of five missions, namely Microwave Sounding Mission (MWS), Scatterometer mission (SCA), Radio Occultation mission (RO), Microwave Imaging mission (MWI), Ice Cloud Imaging (ICI) mission, and Multiviewing, Multi-channel, Multi-polarization imaging mission (3MI). This paper will present the instrument main design elements of the 3MI mission, primarily aimed at providing aerosol characterization for climate monitoring, Numerical Weather Prediction (NWP), atmospheric chemistry and air quality. The 3MI instrument is a passive radiometer measuring the polarized radiances reflected by the Earth under different viewing geometries and across several spectral bands spanning the visible and short-wave infrared spectrum. The paper will present the main performances of the instrument and will concentrate mainly on the performance improvements with respect to its heritage derived by the POLDER instrument. The engineering of some key performance requirements (multiviewing, polarization sensitivity, etc.) will also be discussed.

  16. Susceptibility of redbanded and conchuela stink bugs from the Texas Lower Rio Grande Valley to organophosphate and pyrethroid insecticides

    USDA-ARS?s Scientific Manuscript database

    We report the susceptibility of 2 stink bug species, red banded stink bug (RBSB), Piezodorus guildinii, (Westwood) and conchuela stinkbug, Chlorochroa ligata (Say) collected in the Texas Lower Rio Grande Valley to selected pyrethroid and organophosphate technical grade insecticides. The adult glass ...

  17. Detection of vapor-phase organophosphate threats using wearable conformable integrated epidermal and textile wireless biosensor systems.

    PubMed

    Mishra, Rupesh K; Martín, Aida; Nakagawa, Tatsuo; Barfidokht, Abbas; Lu, Xialong; Sempionatto, Juliane R; Lyu, Kay Mengjia; Karajic, Aleksandar; Musameh, Mustafa M; Kyratzis, Ilias L; Wang, Joseph

    2018-03-15

    Flexible epidermal tattoo and textile-based electrochemical biosensors have been developed for vapor-phase detection of organophosphorus (OP) nerve agents. These new wearable sensors, based on stretchable organophosphorus hydrolase (OPH) enzyme electrodes, are coupled with a fully integrated conformal flexible electronic interface that offers rapid and selective square-wave voltammetric detection of OP vapor threats and wireless data transmission to a mobile device. The epidermal tattoo and textile sensors display a good reproducibility (with RSD of 2.5% and 4.2%, respectively), along with good discrimination against potential interferences and linearity over the 90-300mg/L range, with a sensitivity of 10.7µA∙cm 3 ∙mg -1 (R 2 = 0.983) and detection limit of 12mg/L in terms of OP air density. Stress-enduring inks, used for printing the electrode transducers, ensure resilience against mechanical deformations associated with textile and skin-based on-body sensing operations. Theoretical simulations are used to estimate the OP air density over the sensor surface. These fully integrated wearable wireless tattoo and textile-based nerve-agent vapor biosensor systems offer considerable promise for rapid warning regarding personal exposure to OP nerve-agent vapors in variety of decentralized security applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology.

    PubMed

    Mullen, Brian R; Ross, Brennan; Chou, Joan Wang; Khankan, Rana; Khialeeva, Elvira; Bui, Kimberly; Carpenter, Ellen M

    2016-06-01

    Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors-reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon-gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice. In the current study, we examine the consequences of these factors on reelin protein expression and neuronal cell morphology in adult mice. While the cell populations that express reelin in the adult brain appear unchanged in location and distribution, the levels of full length and cleaved reelin protein show persistent reductions following prenatal exposure to chlorpyrifos oxon. Cell positioning and organization in the hippocampus and cerebellum are largely normal in animals with either reduced reelin expression or prenatal exposure to chlorpyrifos oxon, but cellular complexity and dendritic spine organization is altered, with a skewed distribution of immature dendritic spines in adult animals. Paradoxically, combinatorial exposure to both factors appears to generate a rescue of the dendritic spine phenotypes, similar to the mitigation of behavioral and morphological changes observed in our prior study. Together, our observations support an interaction between reelin expression and chlorpyrifos oxon exposure that is not simply additive, suggesting a complex interplay between genetic and environmental factors in regulating brain morphology. © The Author(s) 2016.

  19. Quantitative trait locus mapping and functional genomics of an organophosphate resistance trait in the western corn rootworm, Diabrotica virgifera virgifera.

    PubMed

    Coates, B S; Alves, A P; Wang, H; Zhou, X; Nowatzki, T; Chen, H; Rangasamy, M; Robertson, H M; Whitfield, C W; Walden, K K; Kachman, S D; French, B W; Meinke, L J; Hawthorne, D; Abel, C A; Sappington, T W; Siegfried, B D; Miller, N J

    2016-02-01

    The western corn rootworm, Diabrotica virgifera virgifera, is an insect pest of corn and population suppression with chemical insecticides is an important management tool. Traits conferring organophosphate insecticide resistance have increased in frequency amongst D. v. virgifera populations, resulting in the reduced efficacy in many corn-growing regions of the USA. We used comparative functional genomic and quantitative trait locus (QTL) mapping approaches to investigate the genetic basis of D. v. virgifera resistance to the organophosphate methyl-parathion. RNA from adult methyl-parathion resistant and susceptible adults was hybridized to 8331 microarray probes. The results predicted that 11 transcripts were significantly up-regulated in resistant phenotypes, with the most significant (fold increases ≥ 2.43) being an α-esterase-like transcript. Differential expression was validated only for the α-esterase (ST020027A20C03), with 11- to 13-fold greater expression in methyl-parathion resistant adults (P < 0.05). Progeny with a segregating methyl-parathion resistance trait were obtained from a reciprocal backcross design. QTL analyses of high-throughput single nucleotide polymorphism genotype data predicted involvement of a single genome interval. These data suggest that a specific carboyxesterase may function in field-evolved corn rootworm resistance to organophosphates, even though direct linkage between the QTL and this locus could not be established. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  20. Development of the Electrochemical Biosensor for Organophosphate Chemicals Using CNT/Ionic Liquid Bucky Gel Electrode

    DTIC Science & Technology

    2010-04-01

    www.elsevier .com/locate /e lecomDevelopment of the electrochemical biosensor for organophosphate chemicals using CNT/ ionic liquid bucky gel electrode Bong...hydrolase Ionic liquid CNT Electrochemical property1388-2481/$ - see front matter 2009 Elsevier B.V. A doi:10.1016/j.elecom.2009.01.006 * Corresponding...kaist.ac.kr (S.Y. Lee), whhOrganophosphorus hydrolase (OPH) immobilized on CNT/ ionic liquid (IL) electrodes were prepared by using three different intrinsic

  1. Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a high-risk cohort.

    PubMed

    Philippat, Claire; Barkoski, Jacqueline; Tancredi, Daniel J; Elms, Bill; Barr, Dana Boyd; Ozonoff, Sally; Bennett, Deborah H; Hertz-Picciotto, Irva

    2018-04-01

    Organophosphates are widely used pesticides that have been shown to affect child neurodevelopment. Previous studies that explored their potential effects on Autism Spectrum Disorder (ASD) relied either on proxies of external exposure or on questionnaires completed by the parents to identify autism-like behaviors but did not provide a clinical diagnosis of ASD. We studied the associations between prenatal biologic markers for exposure to organophosphate pesticides and the risk of having a child with ASD or other developmental concerns (ODC). We analyzed 203 mother-child pairs of the ongoing MARBLES (Markers of Autism Risk in Babies - Learning Early Signs) mother-child cohort, which enrolls mothers who are either pregnant or planning a pregnancy and whose expected child has an elevated risk to develop ASD. Seven metabolites of organophosphate pesticides were assessed in repeated urine samples collected during pregnancy. At 36 months, children were assessed with intruments measuring cognitive function and adaptive behaviors, and with two gold-standard diagnostic instruments for ASD: the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. Children were classified in one of the following groups: ASD (n = 46), ODC (n = 55) and typically developing (TD, n = 102). After adjustment for potential confounders, organophosphate metabolite concentrations were not associated with an increased risk of ASD or ODC when boys and girls were studied together. After stratification by sex, dimethylthiophosphate (DMTP) pregnancy concentration tended to be associated with an increased ASD risk among girls (OR for a doubling in the DMTP concentration: 1.64 (95%CI, 0.95; 2.82)) but not among boys (OR: 0.84, 95%CI: 0.63; 1.11). This is the first study of clinically confirmed diagnoses of ASD that utilized repeated measurements of organophosphate metabolites during pregnancy to explore the associations between these pesticides and ASD risk in

  2. Ecotoxicologic impacts of agricultural drain water in the Salinas River, California, USA.

    PubMed

    Anderson, Brian S; Hunt, John W; Phillips, Bryn M; Nicely, Patricia A; Gilbert, Kristine D; de Vlaming, Victor; Connor, Valerie; Richard, Nancy; Tjeerdema, Ronald S

    2003-10-01

    The Salinas River is the largest of the three rivers that drain into the Monterey Bay National Marine Sanctuary in central California (USA). Large areas of this watershed are cultivated year-round in row crops, and previous laboratory studies have demonstrated that acute toxicity of agricultural drain water to Ceriodaphnia dubia is caused by the organophosphate (OP) pesticides chlorpyrifos and diazinon. We investigated chemical contamination and toxicity in waters and sediments in the river downstream of an agricultural drain water input. Ecological impacts of drain water were investigated by using bioassessments of macroinvertebrate community structure. Toxicity identification evaluations were used to characterize chemicals responsible for toxicity. Salinas River water downstream of the agricultural drain was acutely toxic to the cladoceran Ceriodaphnia dubia, and toxicity to C. dubia was highly correlated with combined toxic units (TUs) of chlorpyrifos and diazinon. Laboratory tests were used to demonstrate that sediments in this system were acutely toxic to the amphipod Hyalella azteca, a resident invertebrate. Toxicity identification evaluations (TIEs) conducted on sediment pore water suggested that toxicity to amphipods was due in part to OP pesticides; concentrations of chlorpyrifos in pore water sometimes exceeded the 10-d mean lethal concentration (LC50) for H. azteca. Potentiation of toxicity with addition of the metabolic inhibitor piperonyl butoxide suggested that sediment toxicity also was due to other non-metabolically activated compounds. Macroinvertebrate community structure was highly impacted downstream of the agricultural drain input, and a number of macroinvertebrate community metrics were negatively correlated with combined TUs of chlorpyrifos and diazinon, as well as turbidity associated with the drain water. Some macroinvertebrate metrics were also correlated with bank vegetation cover. This study suggests that pesticide pollution is the

  3. Genotoxicity following Organophosphate Pesticides Exposure among Orang Asli Children Living in an Agricultural Island in Kuala Langat, Selangor, Malaysia.

    PubMed

    Sutris, J M; How, V; Sumeri, S A; Muhammad, M; Sardi, D; Mohd Mokhtar, M T; Muhammad, H; Ghazi, H F; Isa, Z M

    2016-01-01

    Agriculture is an important sector for the Malaysian economy. The use of pesticides in agriculture is crucial due to its function in keeping the crops from harmful insects. Children living near agricultural fields are at risk of pesticide poisoning. To evaluate the genotoxic risk among children who exposed to pesticides and measure DNA damage due to pesticides exposure. In a cross-sectional study 180 Orang Asli Mah Meri children aged between 7 and 12 years were studied. They were all living in an agricultural island in Kuala Langat, Selangor, Malaysia. The data for this study were collected via modified validated questionnaire and food frequency questionnaire, which consisted of 131 food items. 6 urinary organophosphate metabolites were used as biomarkers for pesticides exposure. For genotoxic risk or genetic damage assessment, the level of DNA damage from exfoliated buccal mucosa cells was measured using the comet assay electrophoresis method. Out of 180 respondents, 84 (46.7%) showed positive traces of organophosphate metabolites in their urine. Children with detectable urinary pesticide had a longer tail length (median 43.5; IQR 30.9 to 68.1 μm) than those with undetectable urinary pesticides (median 24.7; IQR 9.5 to 48.1 μm). There was a significant association between the extent of DNA damage and the children's age, length of residence in the area, pesticides detection, and frequency of apple consumption. The organophosphate genotoxicity among children is associated with the amount of exposure (detectability of urinary pesticide) and length of residence in (exposure) the study area.

  4. [Progress in environmental exposure of organophosphate flame retardants].

    PubMed

    Ding, J J; Yang, F X

    2017-06-06

    Organophosphate flame retardants (OPFRs), which have both great properties of flame retardation and plasticization, are currently widely used as additive flame retardants. Due to the restriction and phase-out of brominated flame retardants (BFRs), the market demand for OPFRs as excellent alternatives of BFRs has been rapid increasing. OPFRs can be slowly released into the environment during production and application. Some OPFRs might be persistent in the environment. As a result, OPFRs have been detected in various matrices in the environment and are expected to accumulate in human body through various pathways. OPFRs may cause adverse effects to human health as some of them have been identified as neurotoxicants, reproductive toxicants and potential carcinogens. The article summarized the occurrence and patterns of OPFRs in various environmental matrices such as air, dust, water, food and so on, and in human specimens, estimates the exposure status through different pathways and body burdens of OPFRs. The expected hotspots of OPFRs were also discussed in the future.

  5. Quantitative trait locus mapping and functional genomics of an organophosphate resistance trait in the western corn rootworm, Diabrotica virgifera virgifera

    USDA-ARS?s Scientific Manuscript database

    The western corn rootworm (WCR), Diabrotica virgifera virgifera, is an insect pest of corn, and population suppression with chemical insecticides is an important management tool. Traits conferring organophosphate insecticide resistance have increased in frequency among WCR populations, resulting in...

  6. Prevalence, Circumstances, and Management of Acute Pesticide Poisoning in Hospitals in Kampala City, Uganda.

    PubMed

    Ssemugabo, Charles; Halage, Abdullah Ali; Neebye, Ruth Mubeezi; Nabankema, Victoria; Kasule, Massy Moses; Ssekimpi, Deogratius; Jørs, Erik

    2017-01-01

    This study was aimed at assessing prevalence, circumstance, and management of acute pesticide poisoning in hospitals in Kampala. It was a retrospective cross-sectional study that involved reviewing of 739 poisoning patient records from 5 hospitals in Kampala. Of the 739 patients, 212 were due to pesticide poisoning resulting in a prevalence of 28.8%. About 91.4% (191/210) of the cases were due to organophosphate poisoning, 63.3% (133/210) were intentional, and 98.1% (206/210) were exposed through ingestion. Diagnosis was majorly based on poisoning history 91.2% (187/205), and clinical features such as airways, breathing, and circulation examination 48.0% (95/198); nausea and vomiting 42.9% (91/212); muscle weakness 29.7% (63/212); excessive salivation 23.1% (49/212); and confusion 20.3% (43/212). More than half of the patients admitted were treated using atropine 52.3% (113/212). The prevalence of acute pesticide poisoning was high with most managed based on physical and clinical examination.

  7. Prevalence, Circumstances, and Management of Acute Pesticide Poisoning in Hospitals in Kampala City, Uganda

    PubMed Central

    Ssemugabo, Charles; Halage, Abdullah Ali; Neebye, Ruth Mubeezi; Nabankema, Victoria; Kasule, Massy Moses; Ssekimpi, Deogratius; Jørs, Erik

    2017-01-01

    This study was aimed at assessing prevalence, circumstance, and management of acute pesticide poisoning in hospitals in Kampala. It was a retrospective cross-sectional study that involved reviewing of 739 poisoning patient records from 5 hospitals in Kampala. Of the 739 patients, 212 were due to pesticide poisoning resulting in a prevalence of 28.8%. About 91.4% (191/210) of the cases were due to organophosphate poisoning, 63.3% (133/210) were intentional, and 98.1% (206/210) were exposed through ingestion. Diagnosis was majorly based on poisoning history 91.2% (187/205), and clinical features such as airways, breathing, and circulation examination 48.0% (95/198); nausea and vomiting 42.9% (91/212); muscle weakness 29.7% (63/212); excessive salivation 23.1% (49/212); and confusion 20.3% (43/212). More than half of the patients admitted were treated using atropine 52.3% (113/212). The prevalence of acute pesticide poisoning was high with most managed based on physical and clinical examination. PMID:28904524

  8. Unified study of Quality of Service (QoS) in OPS/OBS networks

    NASA Astrophysics Data System (ADS)

    Hailu, Dawit Hadush; Lema, Gebrehiwet Gebrekrstos; Yekun, Ephrem Admasu; Kebede, Samrawit Haylu

    2017-07-01

    With the growth of Internet traffic, an inevitable use of optical networks provide a large bandwidth, fast data transmission rates and Quality of Service (QoS) support. Currently, Optical Burst Switched (OBS)/Optical Packet Switched (OPS) networks are under study as future solutions for addressing the increase demand of Internet traffic. However, due to their high blocking probability in the intermediate nodes they have been delayed in the industries. Packet loss in OBS/OPS networks is mainly occur due to contention. Hence, the contribution of this study is to analyze the file loss ratio (FLR), packet overhead and number of disjoint paths, and processing delay over Coded Packet Transport (CPT) scheme for OBS/OPS network using simulation. The simulations show that CPT scheme reduces the FLR in OBS/OPS network for the evaluated scenarios since the data packets are chopped off into blocks of the data packet for transmission over a network. Simulation results for secrecy and survivability are verified with the help of the analytical model to define the operational range of CPT scheme.

  9. Structural Study of the Complex Stereoselectivity of Human Butyrylcholinesterase for the Neurotoxic V-agents*

    PubMed Central

    Wandhammer, Marielle; Carletti, Eugénie; Van der Schans, Marcel; Gillon, Emilie; Nicolet, Yvain; Masson, Patrick; Goeldner, Maurice; Noort, Daan; Nachon, Florian

    2011-01-01

    Nerve agents are chiral organophosphate compounds (OPs) that exert their acute toxicity by phosphorylating the catalytic serine of acetylcholinesterase (AChE). The inhibited cholinesterases can be reactivated using oximes, but a spontaneous time-dependent process called aging alters the adduct, leading to resistance toward oxime reactivation. Human butyrylcholinesterase (BChE) functions as a bioscavenger, protecting the cholinergic system against OPs. The stereoselectivity of BChE is an important parameter for its efficiency at scavenging the most toxic OPs enantiomer for AChE. Crystals of BChE inhibited in solution or in cristallo with racemic V-agents (VX, Russian VX, and Chinese VX) systematically show the formation of the PS adduct. In this configuration, no catalysis of aging seems possible as confirmed by the three-dimensional structures of the three conjugates incubated over a period exceeding a week. Crystals of BChE soaked in optically pure VXR-(+) and VXS-(−) solutions lead to the formation of the PS and PR adduct, respectively. These structural data support an in-line phosphonylation mechanism. Additionally, they show that BChE reacts with VXR-(+) in the presence of racemic mixture of V-agents, at odds with earlier kinetic results showing a moderate higher inhibition rate for VXS-(−). These combined results suggest that the simultaneous presence of both enantiomers alters the enzyme stereoselectivity. In summary, the three-dimensional data show that BChE reacts preferentially with PR enantiomer of V-agents and does not age, in complete contrast to AChE, which is selectively inhibited by the PS enantiomer and ages. PMID:21454498

  10. Hyperspectral Imagery for Large Area Survey of Organophosphate Pesticides

    DTIC Science & Technology

    2015-03-26

    possible (Simonian et al., 2004). Nanotechnology has the potential for the development of handheld, real-time, and accurate OP detectors ( Goltz et...dx.doi.org.wrs.idm.oclc.org/10.1016/j.talanta.2012.10.016 Goltz , Mark, N.Dong Shik, Kim, Racz, LeeAnn. (2011). Using nanotechnology to detect nerve agents. Air & Space

  11. Study of Inhibition, Reactivation and Aging Processes of Pesticides Using Graphene Nanosheets/Gold Nanoparticles-Based Acetylcholinesterase Biosensor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Lin; Long, Linjuan; Zhang, Weiying

    2012-09-10

    Organophosphate (OP) and carbamate pesticides exert their toxicity via attacking the hydroxyl moiety of serine in the 'active site' of acetylcholinesterase (AChE). In this paper we developed a stable AChE biosensor based on self-assembling AChE to graphene nanosheet (GN)-gold nanoparticles (AuNPs) nanocomposite electrode for investigation of inhibition, reactivation and aging processes of different pesticides. It is confirmed that pesticides can inhibit AChE in a short time. OPs poisoning is treatable with oximes while carbarmates exposure is insensitive to oximes. The proposed electrochemical approach thus provides a new simple tool for comparison of pesticide sensitivity and guide of therapeutic intervention.

  12. Using an object-based grid system to evaluate a newly developed EP approach to formulate SVMs as applied to the classification of organophosphate nerve agents

    NASA Astrophysics Data System (ADS)

    Land, Walker H., Jr.; Lewis, Michael; Sadik, Omowunmi; Wong, Lut; Wanekaya, Adam; Gonzalez, Richard J.; Balan, Arun

    2004-04-01

    This paper extends the classification approaches described in reference [1] in the following way: (1.) developing and evaluating a new method for evolving organophosphate nerve agent Support Vector Machine (SVM) classifiers using Evolutionary Programming, (2.) conducting research experiments using a larger database of organophosphate nerve agents, and (3.) upgrading the architecture to an object-based grid system for evaluating the classification of EP derived SVMs. Due to the increased threats of chemical and biological weapons of mass destruction (WMD) by international terrorist organizations, a significant effort is underway to develop tools that can be used to detect and effectively combat biochemical warfare. This paper reports the integration of multi-array sensors with Support Vector Machines (SVMs) for the detection of organophosphates nerve agents using a grid computing system called Legion. Grid computing is the use of large collections of heterogeneous, distributed resources (including machines, databases, devices, and users) to support large-scale computations and wide-area data access. Finally, preliminary results using EP derived support vector machines designed to operate on distributed systems have provided accurate classification results. In addition, distributed training time architectures are 50 times faster when compared to standard iterative training time methods.

  13. IT Software Development and IT Operations Strategic Alignment: An Agile DevOps Model

    ERIC Educational Resources Information Center

    Hart, Michael

    2017-01-01

    Information Technology (IT) departments that include development and operations are essential to develop software that meet customer needs. DevOps is a term originally constructed from software development and IT operations. DevOps includes the collaboration of all stakeholders such as software engineers and systems administrators involved in the…

  14. Biosensor Based on Self-Assembling Acetylcholinesterase on Carbon Nanotubes for Flow injection/Amperometric Detection of Organophosphate Pesticides and Nerve Agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Guodong; Lin, Yuehe

    A highly sensitive flow-injection amperometric biosensor for organophosphate pesticides and nerve agents based on self-assembly of acetylcholinesterase (AChE) on carbon nanotube (CNT)-modified glassy carbon (GC) electrode is described. AChE is immobilized on the negatively-charged CNT surface by alternatively assembling a cationic polydiallyldimethylammonium chloride (PDDA) layer and an AChE layer. Transmission electron microscopy images confirm the formation of layer-by-layer nanostructures on carboxyl functionalized CNTs. The unique sandwich-like structure (PDDA/AChE/PDDA) on the CNT surface formed by self-assembly provides a favorable microenvironment to keep the bioactivity of AChE and to prevent enzyme molecule leakage. The electrocatalytic activity of CNT leads to a greatlymore » improved electrochemical detection of the enzymatically generated thiocholine product, including a low oxidation overvoltage (+150 mV), higher sensitivity, and stability. The developed PDDA/AChE/PDDA/CNT/GC biosensor integrated into a flow injection system was used to monitor organophosphate pesticides and nerve agents, such as paraoxon. The sensor performance, including inhibition time and regeneration conditions, was optimized with respect to operating conditions. Under the optimal conditions, the biosensor was used to measure as low as 0.4 pM paraoxon with a 6-min inhibition time. The biosensor had excellent operational lifetime stability with no decrease in the activity of enzymes for more than 20 repeated measurements over a 1-week period. The developed biosensor system is an ideal tool for online monitoring of organophosphate pesticides and nerve agents.« less

  15. Placental oxidative status in rural residents environmentally exposed to organophosphates.

    PubMed

    Chiapella, Graciela; Genti-Raimondi, Susana; Magnarelli, Gladis

    2014-07-01

    The impact of environmental organophosphate pesticide exposure on the placenta oxidative status was assessed. Placental samples were collected from women residing in an agricultural area during pesticide pulverization period, non-pulverization period and from control group. Carboxylesterase activity was significantly decreased in pulverization period group. Enzymatic and non-enzymatic defense system, the oxidative stress biomarkers and the nuclear factor erythroid 2-related factor levels showed no differences among groups. However, in the pulverization period group, an inverse association between catalase activity and placental index, a useful metric for estimating placental inefficiency, was found. This result suggests that catalase may serve as a potential placental biomarker of susceptibility to pesticides. Further studies designed from a gene-environment perspective are needed. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Monocrotophos and dicrotophos residues in birds as a result of misuse of organophosphates in Matagorda county Texas USA

    USGS Publications Warehouse

    Flickinger, Edward L.; White, D.H.; Mitchell, C.A.; Lamont, T.G.

    1984-01-01

    About 1100 birds of 12 spp. [Red-winged blackbird (Agelaius phoeniceus), great-tailed grackle (Quiscalus mexicanus), brown-headed cowbird (Molothrus ater), mourning dove (Zenaida macrours), Eastern meadowlark (Sturnella magna), vesper sparrow (Pooecetes gramineus), common snipe (Gallinago gallinago), blue-winged teal (Anas discors), mottled duck (Anas fulvigula), common moorhen (Gallinula chloropus), redhead (Aythya americana) and ruddy turnstone (Arenaria interpres)] died from organophosphate poisoning in Matagorda County on the Texas Gulf Coast in March and May 1982. Birds died from feeding on rice seed that was illegally treated with dicrotophos or monocrotophos and placed near rice fields as bait to attract and kill birds. Brain acetylcholinesterase inhibition of affected birds averaged 87% (range 82-89%), and contents of gastrointestinal tracts contained residues of dicrotophos (5.6-14 ppm) or monocrotophos (2.1-13 ppm). Rice seed collected at mortality sites contained 210 ppm dicrotophos or 950 ppm monocrotophos. Mortality from dicrotophos poisoning continued for almost 3 wk. The practice of illegally treating rice seed with either of the 2 organophosphates appears to be infrequent but widespread at present.

  17. Evaluating Cumulative OP Pesticide Body Burden of Children: A National Case Study

    PubMed Central

    Payne-Sturges, Devon; Cohen, Jonathan; Castorina, Rosemary; Axelrad, Daniel A.; Woodruff, Tracey J.

    2009-01-01

    Biomonitoring is a valuable tool for identifying exposures to chemicals that pose potential harm to human health. However, to date there has been little published on ways to evaluate the relative public health significance of biomonitoring data for different chemicals, and even less on cumulative assessment of multiple chemicals. The objectives of our study are to develop a methodology for a health risk interpretation of biomonitoring data, and to apply it using NHANES 1999–2002 body burden data for organophosphorus (OP) pesticides. OP pesticides present a particularly challenging case given the non-specificity of many metabolites monitored through NHANES. We back-calculate OP pesticide exposures from urinary metabolite data, and compare cumulative dose estimates with available toxicity information for a common mechanism of action (brain cholinesterase inhibition) using data from U.S. EPA. Our results suggest that approximately 40% of children in the United States may have had insufficient margins of exposure (MOEs) for neurological impacts from cumulative exposures to OP pesticides (MOE less than 1,000). Limitations include uncertainty related to assumptions about likely precursor pesticide compounds of the urinary metabolites, sources of exposure, and intra-individual and temporal variability. PMID:19921915

  18. Acquisition of a Laser Scanning Confocal Microscope to Examine CNS Activity of Antidotal Oximes and to Enhance Undergraduate Research Training Across the Sciences

    DTIC Science & Technology

    2016-07-15

    Activity of Antidotal Oximes and to Enhance Undergraduate Research Training Across the Sciences The views, opinions and/or findings contained in this...to Examine CNS Activity of Antidotal Oximes and to Enhance Undergraduate Research Training Across the Sciences Report Title The project utilized...examining the ability of antidotal oximes to rescue organophosphate (OP)-induced CNS toxicity and training across the sciences and social sciences at

  19. Association of health symptoms with low-level exposure to organophosphates, DNA damage, AChE activity, and occupational knowledge and practice among rice, corn, and double-crop farmers

    PubMed Central

    Hongsibsong, Surat; Sittitoon, Nalin; Sapbamrer, Ratana

    2017-01-01

    Objectives: This study aims to determine (1) total dialkylphosphate (ΣDAP) levels, occupational knowledge and practice, DNA damage, AChE activity, and health symptoms in rice, corn, and double-crop farmers; (2) the association of health symptoms with ΣDAP levels, occupational knowledge and practice, DNA damage, and AChE activity in farmers; and (3) the prevalence of health symptoms between farmers and non-farmers. Methods: A cross-sectional study was conducted by interviewing as well as analyzing urine and blood samples during July to August 2014. Results: There were no differences in ΣDAP levels, AChE activity, and occupational knowledge and practice scores among all farmer groups. In terms of health symptoms related to ΣDAP, AChE activity, DNA damage, and occupational knowledge and practice, pesticide-related symptoms were determined, including breathlessness, chest pain, dry throat, numbness, muscle weakness, cramp, headache, dizziness, eye irritation, white/red rash, and white/red pimple, which were classified as respiratory, muscle, nervous, and epithelial symptoms. A remarkable finding was that farmers had a significantly higher prevalence of muscle weakness (odds ratio (OR)=3.79) and numbness (OR=3.45) as compared with non-farmers. Conclusion: Our findings, therefore, suggest that a long-term low-level exposure to organophosphates (OPs) may be associated with an increasing prevalence of muscle symptoms. However, a further cohort study incorporating sensitive health outcomes and measurement of multiple pesticides monitoring on a larger scale is warranted. PMID:28077823

  20. Association of health symptoms with low-level exposure to organophosphates, DNA damage, AChE activity, and occupational knowledge and practice among rice, corn, and double-crop farmers.

    PubMed

    Hongsibsong, Surat; Sittitoon, Nalin; Sapbamrer, Ratana

    2017-03-28

    This study aims to determine (1) total dialkylphosphate (ΣDAP) levels, occupational knowledge and practice, DNA damage, AChE activity, and health symptoms in rice, corn, and double-crop farmers; (2) the association of health symptoms with ΣDAP levels, occupational knowledge and practice, DNA damage, and AChE activity in farmers; and (3) the prevalence of health symptoms between farmers and non-farmers. A cross-sectional study was conducted by interviewing as well as analyzing urine and blood samples during July to August 2014. There were no differences in ΣDAP levels, AChE activity, and occupational knowledge and practice scores among all farmer groups. In terms of health symptoms related to ΣDAP, AChE activity, DNA damage, and occupational knowledge and practice, pesticide-related symptoms were determined, including breathlessness, chest pain, dry throat, numbness, muscle weakness, cramp, headache, dizziness, eye irritation, white/red rash, and white/red pimple, which were classified as respiratory, muscle, nervous, and epithelial symptoms. A remarkable finding was that farmers had a significantly higher prevalence of muscle weakness (odds ratio (OR)=3.79) and numbness (OR=3.45) as compared with non-farmers. Our findings, therefore, suggest that a long-term low-level exposure to organophosphates (OPs) may be associated with an increasing prevalence of muscle symptoms. However, a further cohort study incorporating sensitive health outcomes and measurement of multiple pesticides monitoring on a larger scale is warranted.

  1. Eye movement instructions modulate motion illusion and body sway with Op Art

    PubMed Central

    Kapoula, Zoï; Lang, Alexandre; Vernet, Marine; Locher, Paul

    2015-01-01

    Op Art generates illusory visual motion. It has been proposed that eye movements participate in such illusion. This study examined the effect of eye movement instructions (fixation vs. free exploration) on the sensation of motion as well as the body sway of subjects viewing Op Art paintings. Twenty-eight healthy adults in orthostatic stance were successively exposed to three visual stimuli consisting of one figure representing a cross (baseline condition) and two Op Art paintings providing sense of motion in depth—Bridget Riley’s Movements in Squares and Akiyoshi Kitaoka’s Rollers. Before their exposure to the Op Art images, participants were instructed either to fixate at the center of the image (fixation condition) or to explore the artwork (free viewing condition). Posture was measured for 30 s per condition using a body fixed sensor (accelerometer). The major finding of this study is that the two Op Art paintings induced a larger antero-posterior body sway both in terms of speed and displacement and an increased motion illusion in the free viewing condition as compared to the fixation condition. For body sway, this effect was significant for the Riley painting, while for motion illusion this effect was significant for Kitaoka’s image. These results are attributed to macro-saccades presumably occurring under free viewing instructions, and most likely to the small vergence drifts during fixations following the saccades; such movements in interaction with visual properties of each image would increase either the illusory motion sensation or the antero-posterior body sway. PMID:25859197

  2. Eye movement instructions modulate motion illusion and body sway with Op Art.

    PubMed

    Kapoula, Zoï; Lang, Alexandre; Vernet, Marine; Locher, Paul

    2015-01-01

    Op Art generates illusory visual motion. It has been proposed that eye movements participate in such illusion. This study examined the effect of eye movement instructions (fixation vs. free exploration) on the sensation of motion as well as the body sway of subjects viewing Op Art paintings. Twenty-eight healthy adults in orthostatic stance were successively exposed to three visual stimuli consisting of one figure representing a cross (baseline condition) and two Op Art paintings providing sense of motion in depth-Bridget Riley's Movements in Squares and Akiyoshi Kitaoka's Rollers. Before their exposure to the Op Art images, participants were instructed either to fixate at the center of the image (fixation condition) or to explore the artwork (free viewing condition). Posture was measured for 30 s per condition using a body fixed sensor (accelerometer). The major finding of this study is that the two Op Art paintings induced a larger antero-posterior body sway both in terms of speed and displacement and an increased motion illusion in the free viewing condition as compared to the fixation condition. For body sway, this effect was significant for the Riley painting, while for motion illusion this effect was significant for Kitaoka's image. These results are attributed to macro-saccades presumably occurring under free viewing instructions, and most likely to the small vergence drifts during fixations following the saccades; such movements in interaction with visual properties of each image would increase either the illusory motion sensation or the antero-posterior body sway.

  3. Nanoparticle-Based Immunochromatographic Test Strip with Fluorescent Detector for Quantification of Phosphorylated Acetycholinesterase: An Exposure Biomarker of Organophosphorous Agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Weiying; Ge, Xiaoxiao; Tang, Yong

    A nanoparticle-based fluorescence immunochromatographic test strip (FITS) coupled with a hand-held detector for highly selective and sensitive detection of phosphorylated acetylcholinesterase (AChE), an exposure biomarker of organophosphate (OP) pesticides and nerve agents, is reported. In this approach, OP-AChE adducts were selectively captured by quantum dot-tagged anti-AChE antibodies (Qdot-anti-AChE) and zirconia nanoparticles (ZrO2 NPs). The sandwich-like immunoreactions were performed among the Qdot-anti-AChE, OP-AChE and ZrO2 NPs to form Qdot-anti-AChE/OP-AChE/ZrO2 complex, which was detected by recording the fluorescence intensity of Qdot captured on the test line. Paraoxon was used as the model OP pesticides. Under optimal conditions, this portable FITS immunosensor demonstratesmore » a highly linear absorption response over the range of 0.01 nM to 10 nM OP-AChE, with a detection limit of 4 pM, coupled with a good reproducibility. Moreover, the FITS immunosensor has been validated with OP-AChE spiked human plasma samples. This is the first report on the development of ZrO2 NPs-based FITS for detection of OP-AChE adduct. The FITS immunosensor provides a sensitive and low-cost sensing platform for on-site screening/evaluating OP pesticides and nerve agents poisoning.« less

  4. The Vida Verde Women's Co-Op: Brazilian immigrants organizing to promote environmental and social justice.

    PubMed

    Gute, David M; Siqueira, Eduardo; Goldberg, Julia S; Galvão, Heloisa; Chianelli, Mônica; Pirie, Alex

    2009-11-01

    We reviewed the key steps in the launch of the Vida Verde Women's Co-Op among Brazilian immigrant housecleaners in Somerville, MA. The co-op provides green housecleaning products, encourages healthy work practices, and promotes a sense of community among its members. We conducted in-depth interviews with 8 of the first co-op members, who reported a reduction in symptoms associated with the use of traditional cleaning agents and a new sense of mutual support. Critical to the co-op's success have been the supportive roles of its academic partners (Tufts University and the University of Massachusetts, Lowell), effective media outreach, and a focus on advancing social justice. Next steps include implementing a formal business plan and assessing the appropriateness of cooperatives in other industries.

  5. 48 CFR 750.7110-3 - Submission of cases to the M/OP Director.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... M/OP Director. 750.7110-3 Section 750.7110-3 Federal Acquisition Regulations System AGENCY FOR... Actions To Protect Foreign Policy Interests of the United States 750.7110-3 Submission of cases to the M/OP Director. Cases to be submitted for consideration by the M/OAA Director shall be prepared and...

  6. 75 FR 16874 - Market Test of “Samples Co-Op Box” Experimental Product

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-02

    ... POSTAL SERVICE Market Test of ``Samples Co-Op Box'' Experimental Product AGENCY: Postal Service TM . ACTION: Notice. SUMMARY: The Postal Service gives notice of a market test of an experimental product in... pursuant to 39 U.S.C. 3641(c)(1) that it will begin a market test of its ``Samples Co-Op Box'' experimental...

  7. Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in class III furcation defects.

    PubMed

    Giannobile, W V; Ryan, S; Shih, M S; Su, D L; Kaplan, P L; Chan, T C

    1998-02-01

    Osteogenic protein-1 (OP-1) is a member of the transforming growth factor beta superfamily and is a potent modulator of osteogenesis and bone cell differentiation. This preclinical study in dogs sought to assess the effects of OP-1 on periodontal wound healing in surgically created critical size Class III furcation defects. Eighteen male beagle dogs were subjected to the creation of bilateral mandibular 5 mm osseous defects. A split-mouth design was utilized which randomly assigned opposing quadrants to control therapy (surgery alone or collagen vehicle) or 1 of 3 ascending concentrations of OP-1 in a collagen vehicle (0.75 mg OP-1/g collagen, 2.5 mg/g, or 7.5 mg/g). Thus, 9 quadrants per test group received OP-1, 9 quadrants per control group received surgery alone, and 9 quadrants received collagen vehicle alone. Test articles were delivered by a surgeon masked to the treatment, and fluorogenic bone labels were injected at specified intervals post-treatment. Eight weeks after defect creation and OP-1 delivery, tissue blocks of the mandibulae were taken for masked histomorphometric analysis to assess parameters of periodontal regeneration (e.g., bone height, bone area, new attachment formation, and percent of defect filled with new bone). Histomorphometry revealed limited evidence of osteogenesis, cementogenesis, and new attachment formation in either vehicle or surgery-alone sites. In contrast, sites treated with all 3 concentrations of OP-1 showed pronounced stimulation of osteogenesis, regenerative cementum, and new attachment formation. Lesions treated with 7.5 mg/g of OP-1 in collagen regenerated 3.9+/-1.7 mm and 6.1+/-3.4 mm2 (mean +/-S.D.) of linear bone height and bone area, respectively. Furthermore, these differences were statistically different from both control therapies for all wound healing parameters (P < 0.0001). No significant increase in tooth root ankylosis was found among the treatment groups when compared to the surgery-alone group. We

  8. Phosphonium-Organophosphate Ionic Liquids as Lubricant Additives: Effects of Cation Structure on Physicochemical and Tribological Characteristics

    DOE PAGES

    Barnhill, William C.; Qu, Jun; Luo, Huimin; ...

    2014-11-17

    In our previous work we suggest great potential for a phosphonium-organophosphate ionic liquid (IL) as an antiwear lubricant additive. In this study, a set of five ILs were carefully designed and synthesized, with identical organophosphate anions but dissimilar phosphonium cations, to allow systematic investigation of the effects of cation alkyl chain length and symmetry on physicochemical and tribological properties. Symmetric cations with shorter alkyl chains seem to increase the density and thermal stability due to closer packing. On the other hand, either higher cation symmetry or longer alkyl moieties induce a higher viscosity, though the viscosity index is dependent moremore » on molecular mass than on symmetry. While a larger cation size generally increases an IL’s solubility in nonpolar hydrocarbon oils, six-carbon seems to be the critical minimum alkyl chain length for high oil miscibility. Both the two ILs, that are mutually oil miscible, have demonstrated promising lubricating performance at 1.04% treat rate, though the symmetric-cation IL moderately outperformed the asymmetric-cation IL. Moreover, characterizations on the tribofilm formed by the best-performing symmetric-cation IL revealed the film thickness, nanostructure, and chemical composition. Our results provide fundamental insights for future molecular design in developing oil-soluble ILs as lubricant additives.« less

  9. Towards Understanding the Catalytic Mechanism of Human Paraoxonase 1: Experimental and In Silico Mutagenesis Studies.

    PubMed

    Tripathy, Rajan K; Aggarwal, Geetika; Bajaj, Priyanka; Kathuria, Deepika; Bharatam, Prasad V; Pande, Abhay H

    2017-08-01

    Human paraoxonase 1 (h-PON1) is a ~45-kDa serum enzyme that can hydrolyze a variety of substrates, including organophosphate (OP) compounds. It is a potential candidate for the development of antidote against OP poisoning in humans. However, insufficient OP-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced OP-hydrolyzing activity. The crystal structure of h-PON1 remains unsolved, and the molecular details of how the enzyme catalyses hydrolysis of different types of substrates are also not clear. Understanding the molecular details of the catalytic mechanism of h-PON1 is essential to engineer better variant(s) of enzyme. In this study, we have used a random mutagenesis approach to increase the OP-hydrolyzing activity of recombinant h-PON1. The mutants not only showed a 10-340-fold increased OP-hydrolyzing activity against different OP substrates but also exhibited differential lactonase and arylesterase activities. In order to investigate the mechanistic details of the effect of observed mutations on the hydrolytic activities of enzyme, molecular docking studies were performed with selected mutants. The results suggested that the observed mutations permit differential binding of substrate/inhibitor into the enzyme's active site. This may explain differential hydrolytic activities of the enzyme towards different substrates.

  10. Case Control Study of Impulsivity, Aggression, Pesticide Exposure and Suicide Attempts Using Pesticides among Farmers.

    PubMed

    Lyu, Chun Ping; Pei, Jian Ru; Beseler, L Cheryl; Li, Yu Ling; Li, Jian Hui; Ren, Ming; Stallones, Lorann; Ren, Shu Ping

    2018-03-01

    A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. Questionnaires were used to collect information; impulsivity and aggression were measured by the Barratt Impulsivity Scale (BIS) and the Aggression Inventory (AI). A greater number of OP symptoms was associated with an increased odds of a suicide attempt after adjusting for marital status and income (OR = 1.45; CI 1.14-1.86). Attempted suicide was significantly associated with high impulsivity scores (means: 72.4 vs. 60.6, P < 0.0001) and high aggression scores (means: 38.5 vs. 26.1, P < 0.0001). Suicide attempters had a higher number of OP exposure symptoms than controls and scored higher on scales of impulsivity and aggression. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  11. Creativity and Technology in Mathematics: From Story Telling to Algorithmic with Op'Art

    ERIC Educational Resources Information Center

    Mercat, Christian; Filho, Pedro Lealdino; El-Demerdash, Mohamed

    2017-01-01

    This article describes some of the results of the European project mcSquared (http://mc2-project.eu/) regarding the use of Op'Art and optical illusion pieces as a tool to foster modeling and creative mathematical thinking in students. We present briefly the c-book technology and some results we got experimenting it. The Op'Art movement, with…

  12. T-cell differentiation of multipotent hematopoietic cell line EML in the OP9-DL1 coculture system.

    PubMed

    Kutlesa, Snjezana; Zayas, Jennifer; Valle, Alexandra; Levy, Robert B; Jurecic, Roland

    2009-08-01

    Multipotent hematopoietic cell line EML can differentiate into myeloid, erythroid, megakaryocytic, and B-lymphoid lineages, but it remained unknown whether EML cells have T-cell developmental potential as well. The goal of this study was to determine whether the coculture with OP9 stromal cells expressing Notch ligand Delta-like 1 (OP9-DL1) could induce differentiation of EML cells into T-cell lineage. EML cells were cocultured with control OP9 or OP9-DL1 stromal cells in the presence of cytokines (stem cell factor, interleukin-7, and Fms-like tyrosine kinase 3 ligand). Their T-cell lineage differentiation was assessed through flow cytometry and reverse transcription polymerase chain reaction expression analysis of cell surface markers and genes characterizing and associated with specific stages of T-cell development. The phenotypic, molecular, and functional analysis has revealed that in EML/OP9-DL1 cocultures with cytokines, but not in control EML/OP9 cocultures, EML cell line undergoes T-cell lineage commitment and differentiation. In OP9-DL1 cocultures, EML cell line has differentiated into cells that 1) resembled double-negative, double-positive, and single-positive stages of T-cell development; 2) initiated expression of GATA-3, Pre-Talpha, RAG-1, and T-cell receptor-Vbeta genes; and 3) produced interferon-gamma in response to T-cell receptor stimulation. These results support the notion that EML cell line has the capacity for T-cell differentiation. Remarkably, induction of T-lineage gene expression and differentiation of EML cells into distinct stages of T-cell development were very similar to previously described T-cell differentiation of adult hematopoietic stem cells and progenitors in OP9-DL1 cocultures. Thus, EML/OP9-DL1 coculture could be a useful experimental system to study the role of particular genes in T-cell lineage specification, commitment, and differentiation.

  13. OP-Yield Version 1.00 user's guide

    Treesearch

    Martin W. Ritchie; Jianwei Zhang

    2018-01-01

    OP-Yield is a Microsoft Excel™ spreadsheet with 14 specified user inputs to derive custom yield estimates using the original Oliver and Powers (1978) functions as the foundation. It presents yields for ponderosa pine (Pinus ponderosa Lawson & C. Lawson) plantations in northern California. The basic model forms for dominantand...

  14. The Vida Verde Women's Co-Op: Brazilian Immigrants Organizing to Promote Environmental and Social Justice

    PubMed Central

    Siqueira, Eduardo; Goldberg, Julia S.; Galvão, Heloisa; Chianelli, Mônica; Pirie, Alex

    2009-01-01

    We reviewed the key steps in the launch of the Vida Verde Women's Co-Op among Brazilian immigrant housecleaners in Somerville, MA. The co-op provides green housecleaning products, encourages healthy work practices, and promotes a sense of community among its members. We conducted in-depth interviews with 8 of the first co-op members, who reported a reduction in symptoms associated with the use of traditional cleaning agents and a new sense of mutual support. Critical to the co-op's success have been the supportive roles of its academic partners (Tufts University and the University of Massachusetts, Lowell), effective media outreach, and a focus on advancing social justice. Next steps include implementing a formal business plan and assessing the appropriateness of cooperatives in other industries. PMID:19890146

  15. Experimental Measurements for the Effect of Dilution Procedure in Blood Esterases as Animals Biomarker for Exposure to OP Compounds

    PubMed Central

    Abass, Kasim Sakran

    2014-01-01

    Organophosphate compounds can bind to carboxylesterase, which may lower the concentration of organophosphate pesticides at the target site enzyme, cholinesterase. It is unclear from the literature whether it is the carboxylesterase affinity for the organophosphate and/or the number of carboxylesterase molecules that is the dominant factor in determining the protective potential of carboxylesterase. The fundamental dilutions and kinetic effects of esterase enzyme are still poorly understood. This study aims to confirm and extend our current knowledge about the effects of dilutions on esterases activities in the blood for birds with respect to protecting the enzyme from organophosphate inhibition. There was significantly higher esterases activities in dilution 1 : 10 in the all blood samples from quail, duck, and chick compared to other dilutions (1 : 5, 1 : 15, 1 : 20, and 1 : 25) in all cases. Furthermore, our results also pointed to the importance of estimating different dilutions effects prior to using in birds as biomarker tools of environmental exposure. Concentration-inhibition curves were determined for the inhibitor in the presence of dilutions 1 : 5, 1 : 10, plus 1 : 15 (to stimulate carboxylesterase). Point estimates (concentrations calculated to produce 20, 50, and 80% inhibition) were compared across conditions and served as a measure of esterase-mediated detoxification. Results with well-known inhibitors (malathion) were in agreement with the literature, serving to support the use of this assay. Among the thiol-esters dilution 1 : 5 was observed to have the highest specificity constant (k cat/K m), and the K m and k cat values were 176 μM and 16,765 s−1, respectively, for S-phenyl thioacetate ester, while detected in dilution 1 : 15 was the lowest specificity constant (k cat/K m), and the K m and k cat values were 943 μM and 1154 s−1, respectively, for acetylthiocholine iodide ester. PMID:24864243

  16. Connected vehicle pilot deployment program phase 1, concept of operations (ConOps) – Tampa (THEA).

    DOT National Transportation Integrated Search

    2016-02-01

    This document describes the Concept of Operations (ConOps) for the Tampa Hillsborough Expressway Authority (THEA) Connected Vehicle (CV) Pilot Deployment. This ConOps describes the current state of operations, establishes the reasons for change, and ...

  17. Connected vehicle pilot deployment program phase 1, concept of operations (ConOps) - New York City.

    DOT National Transportation Integrated Search

    2016-04-08

    This document describes the Concept of Operations (ConOps) for the New York City Department of Transportation (NYC) Connected Vehicle Pilot Deployment (CVPD) Project. This ConOps describes the current state of operations, establishes the reasons for ...

  18. Synergy between repellents and organophosphates on bed nets: efficacy and behavioural response of natural free-flying An. gambiae mosquitoes.

    PubMed

    Pennetier, Cédric; Costantini, Carlo; Corbel, Vincent; Licciardi, Séverine; Dabiré, Roch K; Lapied, Bruno; Chandre, Fabrice; Hougard, Jean-Marc

    2009-11-19

    Chemicals are used on bed nets in order to prevent infected bites and to kill aggressive malaria vectors. Because pyrethroid resistance has become widespread in the main malaria vectors, research for alternative active ingredients becomes urgent. Mixing a repellent and a non-pyrethroid insecticide seemed to be a promising tool as mixtures in the laboratory showed the same features as pyrethroids. We present here the results of two trials run against free-flying Anopheles gambiae populations comparing the effects of two insect repellents (either DEET or KBR 3023, also known as icaridin) and an organophosphate insecticide at low-doses (pirimiphos-methyl, PM) used alone and in combination on bed nets. We showed that mixtures of PM and the repellents induced higher exophily, blood feeding inhibition and mortality among wild susceptible and resistant malaria vectors than compounds used alone. Nevertheless the synergistic interactions are only involved in the high mortality induced by the two mixtures. These field trials argue in favour of the strategy of mixing repellent and organophosphate on bed nets to better control resistant malaria vectors.

  19. A Mechanism-based 3D-QSAR Approach for Classification ...

    EPA Pesticide Factsheets

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π–π interaction with Trp86

  20. Biomarkers of Sensitivity and Exposure in Washington State Pesticide Handlers

    PubMed Central

    Keifer, M.C.; Checkoway, H.; De Roos, A.J.; Farin, F.M.; Fenske, R.A.; Richter, R.J.; van Belle, G.; Furlong, C.E.

    2011-01-01

    Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are widely used in agriculture in the US and abroad. These compounds – which inhibit acetylcholinesterase (AChE) enzyme activity – continue to be responsible for a high proportion of pesticide poisonings among US agricultural workers. It is possible that some individuals may be especially susceptible to health effects related to OP/CB exposure. The paraoxonase (PON1) enzyme metabolizes the highly toxic oxon forms of some OPs, and an individual's PON1 status may be an important determinant of his or her sensitivity to these chemicals. This chapter discusses methods used to characterize individual PON1 status and reviews previous epidemiologic studies that have evaluated PON1-related sensitivity to OPs in relation to various health endpoints. It also describes an ongoing longitudinal study among OP-exposed agricultural pesticide handlers who are participating in a recently implemented cholinesterase monitoring program in Washington State. This study will evaluate handlers' PON1 status as a hypothesized determinant of butyrylcholinesterase (BuChE) inhibition. Such studies will be useful to determine how regulatory risk assessments might account for differences in PON1-related OP sensitivity when characterizing inter-individual variability in risk related to OP exposure. Recent work assessing newer and more sensitive biomarkers of OP exposure is also discussed briefly in this chapter. PMID:20221867

  1. Designing a Successful Acupuncture Treatment Program for Gulf War Illness

    DTIC Science & Technology

    2017-10-01

    altered white matter microstructural integrity in organophosphate (OP) pesticide, sarin nerve agent and pyridogstigmine bromide (PB) anti-nerve gas... Integration for chronic low back pain" PI: Jacobson (3/4/ 2011-6/21/2013) N = 46. Study Site: Spaulding Rehabilitation Hospital (SRH). In this cohort... integration (SI) plus outpatient rehabili- tation (OR) versus OR alone. The details of the study are described in a recent publication (Jacobson et al

  2. A Preliminary Model for the Protective Role of the Endocannabinoid 2-Arachydonylglycerol in Neuroinflammation

    DTIC Science & Technology

    2015-09-30

    example, Liu et al. (2013) measured the effect of chlorpyrifos (280 mg/kg via subcutaneous (sc) injection) and parathion (27 mg/kg sc) in rats on 2...rats to the organophosphates (OPs) chlorpyrifos (280 mg/kg, sc) and parathion (27 mg/kg, sc), and correspond to 53 and 20 percent predicted inhibition...Effects of Parathion and Chlorpyrifos on Extracellular Endocannabinoid Levels in Rat Hippocampus: Influence on Cholinergic Toxicity. Toxicol Appl

  3. Preparing for High Technology: Successful Co-op Strategies. Research and Development Series No. 263.

    ERIC Educational Resources Information Center

    Franchak, Stephen J.; Smith, O. H. Michael

    This document has been prepared to assist program administrators and practitioners in planning and implementing cooperative (co-op) programs in high technology occupational areas. Information focuses on the key elements, strategies, and procedures of successful co-op programs. The guide contains nine chapters and is based on a review of the…

  4. Upregulated Op18/stathmin activity causes chromosomal instability through a mechanism that evades the spindle assembly checkpoint

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Holmfeldt, Per; Sellin, Mikael E.; Gullberg, Martin, E-mail: Martin.Gullberg@molbiol.umu.se

    2010-07-15

    Op18/stathmin (Op18) is a microtubule-destabilizing protein that is phosphorylation-inactivated during mitosis and its normal function is to govern tubulin subunit partitioning during interphase. Human tumors frequently overexpress Op18 and a tumor-associated Q18{yields}E mutation has been identified that confers hyperactivity, destabilizes spindle microtubules, and causes mitotic aberrancies, polyploidization, and chromosome loss in K562 leukemia cells. Here we determined whether wild-type and mutant Op18 have the potential to cause chromosomal instability by some means other than interference with spindle assembly, and thereby bypassing the spindle assembly checkpoint. Our approach was based on Op18 derivatives with distinct temporal order of activity during mitosis,more » conferred either by differential phosphorylation inactivation or by anaphase-specific degradation through fusion with the destruction box of cyclin B1. We present evidence that excessive Op18 activity generates chromosomal instability through interference occurring subsequent to the metaphase-to-anaphase transition, which reduces the fidelity of chromosome segregation to spindle poles during anaphase. Similar to uncorrected merotelic attachment, this mechanism evades detection by the spindle assembly checkpoint and thus provides an additional route to chromosomal instability.« less

  5. Use of a human skin in vitro model to investigate the influence of 'every-day' clothing and skin surface decontamination on the percutaneous penetration of organophosphates.

    PubMed

    Moore, C A; Wilkinson, S C; Blain, P G; Dunn, M; Aust, G A; Williams, F M

    2014-08-17

    Organophosphates (OPs) are widely used in agriculture. Many studies have investigated the capability of personal protective equipment (PPE) to reduce chemical exposure; however, investigations into the protective effect of 'every-day' clothing are rare. The purpose of this study was to investigate the protective effect of 'every-day' clothing against dermal exposure and to measure early decontamination of skin following exposure to chlorpyrifos and dichlorvos. Using human skin in vitro, absorption of (14)C-labelled chlorpyrifos (500 ng/cm(2)), was shown to be significantly reduced when applied to clothed skin (cotton shirt), regardless of application vehicle (isopropanol (IPA) or propylene glycol (PG)). The majority of applied dose was retained within the clothing after 4 h exposure. Significant reduction in absorption of chlorpyrifos (in PG) was seen through clothed skin when supplemented with skin decontamination at 4 h, compared with clothed skin decontaminated after 24 h, however, this was not observed with IPA. Absorption of dichlorvos (5 μg/cm(2)) was greater through unclothed skin than chlorpyrifos for all vehicles (IPA, isopropyl myristate (IPM) and PG). Significant reduction in absorption was observed when decontaminating clothed skin at 30 min, compared with decontamination at 24 h (post-exposure) for all vehicles. indicate that 'every-day' clothing is effective at reducing exposure to chemicals in contact with skin. Washing the skin surface immediately following removal of exposed clothing can further reduce exposure, depending on the properties of the chemical and vehicle applied. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. The Co-Op/Disadvantaged Job Success Project. Final Report. Vocational-Technical Education Research Report.

    ERIC Educational Resources Information Center

    Welch, Frederick G.; Erwin, Michael

    The Co-op/Disadvantaged First-Job Success Project was organized to provide inservice training to vocational teachers and cooperative education coordinators who work with inner city disadvantaged youth in the south central region of Pennsylvania. The project was organized in a manner that allowed project staff, co-op coordinators, and teachers to…

  7. Influence of polychlorinated aromatic compounds on the biotransformation and toxicity of organophosphorus pesticides (OP) to the Daphnia magna

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tonkopii, V.; Zagrebin, A.; Sherstneva, L.

    1995-12-31

    The effect of different polychlorinated aromatics (DDT, Aroclor 1254, certain polychlorinated biphenyls and dibenzofurans) on the toxicity of OP (DDVP paraoxon, malaoxon) to Daphnia magna was studied. Pretreatment of daphnids with chlorinated compounds during 72 hours in nontoxic concentrations (1/5--1/20 CL{sub 50}) has been shown to reduce the toxicity of OP for hydrobionts. For study of influence of chlorinated compounds on biotransformation of OP the activity of enzymes which are hydrolyzing the OP was investigated in Daphnia`s homogenates or microsomes. The activity of carboxylesterase (tributyrinase, aliesterase) and arylesterase (phosphorylphosphatase) with usage as substrates accordingly {alpha}-naphthylacetate and paraoxon was measured. Besidesmore » that the activity of cholinesterase with application of propionylthiocholine as substrate was determined. After polychlorinated aromatic compounds treatment of daphnids activities of both aryl-and carboxylesterase increased markedly. It decreased the inhibition of Daphnia`s cholinesterase caused by incubation with OP in concentrations 0.5--1.0 CL{sub 50}. Thus the induction by chlorinate aromatics of OP metabolizing enzymes seems to play the important role in reduction of OP toxicity to Daphnia magna. Perhaps the aryl- and carboxylesterase of Daphnia can be used as biomarkers of pollution by polychlorinated aromatics in water.« less

  8. T-cell differentiation of multipotent hematopoietic cell line EML in the OP9-DL1 coculture system

    PubMed Central

    Kutleša, Snježana; Zayas, Jennifer; Valle, Alexandra; Levy, Robert B.; Jurecic, Roland

    2011-01-01

    Objective Multipotent hematopoietic cell line EML can differentiate into myeloid, erythroid, megakaryocytic, and B-lymphoid lineages, but it remained unknown whether EML cells have T-cell developmental potential as well. The goal of this study was to determine whether the coculture with OP9 stromal cells expressing Notch ligand Delta-like 1 (OP9-DL1) could induce differentiation of EML cells into T-cell lineage. Materials and Methods EML cells were cocultured with control OP9 or OP9-DL1 stromal cells in the presence of cytokines (stem cell factor, interleukin-7, and Fms-like tyrosine kinase 3 ligand). Their T-cell lineage differentiation was assessed through flow cytometry and reverse transcription polymerase chain reaction expression analysis of cell surface markers and genes characterizing and associated with specific stages of T-cell development. Results The phenotypic, molecular, and functional analysis has revealed that in EML/OP9-DL1 cocultures with cytokines, but not in control EML/OP9 cocultures, EML cell line undergoes T-cell lineage commitment and differentiation. In OP9-DL1 cocultures, EML cell line has differentiated into cells that 1) resembled double-negative, double-positive, and single-positive stages of T-cell development; 2) initiated expression of GATA-3, Pre-Tα, RAG-1, and T-cell receptor – Vβ genes; and 3) produced interferon-γ in response to T-cell receptor stimulation. Conclusions These results support the notion that EML cell line has the capacity for T-cell differentiation. Remarkably, induction of T-lineage gene expression and differentiation of EML cells into distinct stages of T-cell development were very similar to previously described T-cell differentiation of adult hematopoietic stem cells and progenitors in OP9-DL1 cocultures. Thus, EML/OP9-DL1 coculture could be a useful experimental system to study the role of particular genes in T-cell lineage specification, commitment, and differentiation. PMID:19447159

  9. Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring

    PubMed Central

    2011-01-01

    The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish. PMID:21410251

  10. Theoretical NMR and conformational analysis of solvated oximes for organophosphates-inhibited acetylcholinesterase reactivation

    NASA Astrophysics Data System (ADS)

    da Silva, Jorge Alberto Valle; Modesto-Costa, Lucas; de Koning, Martijn C.; Borges, Itamar; França, Tanos Celmar Costa

    2018-01-01

    In this work, quaternary and non-quaternary oximes designed to bind at the peripheral site of acetylcholinesterase previously inhibited by organophosphates were investigated theoretically. Some of those oximes have a large number of degrees of freedom, thus requiring an accurate method to obtain molecular geometries. For this reason, the density functional theory (DFT) was employed to refine their molecular geometries after conformational analysis and to compare their 1H and 13C nuclear magnetic resonance (NMR) theoretical signals in gas-phase and in solvent. A good agreement with experimental data was achieved and the same theoretical approach was employed to obtain the geometries in water environment for further studies.

  11. Biomarkers of oxidative stress and DNA damage in agricultural workers: A pilot study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Muniz, Juan F.; McCauley, Linda; Scherer, J.

    Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. A study of pesticide applicators and farmworkers was conducted to examine the relationship between organophosphate pesticide exposure and biomarkers of oxidative stress and DNA damage. Urine samples were analyzed for OP metabolites and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Lymphocytes were analyzed for oxidative DNA repair activity and DNA damage (Comet assay), and serum was analyzed for lipid peroxides (i.e., malondialdehyde, MDA). Cellular damage in agricultural workers was validated using lymphocyte cell cultures. Urinary OP metabolites were significantly higher in farmworkers andmore » applicators (p < 0.001) when compared to controls. 8-OH-dG levels were 8.5 times and 2.3 times higher in farmworkers or applicators (respectively) than in controls. Serum MDA levels were 4.9 times and 24 times higher in farmworkers or applicators (respectively) than in controls. DNA damage (Comet assay) and oxidative DNA repair were significantly greater in lymphocytes from applicators and farmworkers when compared with controls. Markers of oxidative stress (i.e., increased reactive oxygen species and reduced glutathione levels) and DNA damage were also observed in lymphocyte cell cultures treated with an OP. The findings from these in vivo and in vitro studies indicate that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. These biomarkers may be useful for increasing our understanding of the link between pesticides and a number of health effects.« less

  12. Screening of organic pollutants in pet hair samples and the significance of environmental factors.

    PubMed

    González-Gómez, Xiana; Cambeiro-Pérez, Noelia; Martínez-Carballo, Elena; Simal-Gándara, Jesús

    2018-06-01

    Organic pollutants (OPs) represent a wide range of chemicals that are potentially harmful for human and wildlife health. Many of these pollutants have been identified as endocrine disruptors that can alter hormonal balance producing adverse biological effects such as neurotoxicity, reproductive disorders, carcinogenicity and hepatotoxicity. For years, hair has been selected as a non-invasive source to assess levels of animal contamination. In the present study, a multiclass screening method for determining about 60 organic pollutants in pet hair was designed and validated for qualitative and quantitative purposes. Concentrations from different classes of organochlorine, and organophosphate pesticides (OCPs, and OPPs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (NDL-PCBs and DL-PCBs), polybrominated diphenyl ethers (PBDEs) and organophosphate esters (OPEs) were identified in the selected pet hair samples from Ourense (NW, Spain). We detected most of these pollutants in the selected hair pets. The mean concentrations found ranged from 89 to 6556ng/g for OPEs, from 8.6 to 1031ng/g for PAHs, from 8.6 to 256ng/g for PBDEs, from 29 to 184ng/g for OPPs, from 0.29 to 139 for OCPs, from 0.30 to 59ng/g for NDL-PCBs and from 1.2 to 14ng/g for DL-PCBs. To our knowledge, this is the first study to document the presence of OPs in pets from North-West Spain and it could provide baseline information for future monitoring of OPs in the area. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Bioactive Paper Sensor Based on the Acetylcholinesterase for the Rapid Detection of Organophosphate and Carbamate Pesticides

    PubMed Central

    Badawy, Mohamed E. I.; El-Aswad, Ahmed F.

    2014-01-01

    In many countries, people are becoming more concerned about pesticide residues which are present in or on food and feed products. For this reason, several methods have been developed to monitor the pesticide residue levels in food samples. In this study, a bioactive paper-based sensor was developed for detection of acetylcholinesterase (AChE) inhibitors including organophosphate and carbamate pesticides. Based on the Ellman colorimetric assay, the assay strip is composed of a paper support (1 × 10 cm), onto which a biopolymer chitosan gel immobilized in crosslinking by glutaraldehyde with AChE and 5,5′-dithiobis(2-nitrobenzoic) acid (DTNB) and uses acetylthiocholine iodide (ATChI) as an outside reagent. The assay protocol involves introducing the sample to sensing zone via dipping of a pesticide-containing solution. Following an incubation period, the paper is placed into ATChI solution to initiate enzyme catalyzed hydrolysis of the substrate, causing a yellow color change. The absence or decrease of the yellow color indicates the levels of the AChE inhibitors. The biosensor is able to detect organophosphate and carbamate pesticides with good detection limits (methomyl = 6.16 × 10−4 mM and profenofos = 0.27 mM) and rapid response times (~5 min). The results show that the paper-based biosensor is rapid, sensitive, inexpensive, portable, disposable, and easy-to-use. PMID:25484901

  14. 75 FR 35816 - Establishment of the Consumer Operated and Oriented Plan (CO-OP) Advisory Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... (CO-OP) Advisory Board AGENCY: Department of Health and Human Services, Office of Consumer Information & Insurance Oversight. ACTION: Federal Register Notice. Authority: The Consumer Operated and Oriented Plan (CO... (PPACA) that calls for the establishment of the Consumer Operated and Oriented Plans (CO-OP) Program...

  15. The pattern of acute poisoning in a teaching hospital, north-west Ethiopia.

    PubMed

    Abula, Teferra; Wondmikun, Yared

    2006-04-01

    Poisoning by means of hazardous chemicals through ignorance, mishap or intentionally is becoming a serious health problem worldwide. Epidemiological data on this important health issue are, however, scarce in Ethiopia. The purpose of this study is to assess the pattern of acute poisonings and determine the approaches employed for the management of poisoning. The medical records of patients with acute poisonings presented to the Gondar University hospital between July 2001 and June 2004 were reviewed retrospectively. One hundred and two patients presenting to the emergency department of the hospital were due to acute poisoning; accounting for about 0.45% of emergency room admissions. Organophosphates, rat poison and alcohol were the commonly encountered poisoning agents (in about 70% of cases) mainly in adults possibly with suicidal or para-suicidal intention. The approaches employed in the management of poisoning mainly involved gastrointestinal decontamination procedures. Specific antidotes were used in a substantial number of patients. The fatality rate was 2.4%. Poisoning with suicidal intention is becoming a serious health problem particularly in adults. Pesticides are commonly used toxicants. The approaches in the management of poisoning are justifiable in some cases. However, much is to be done to improve the recording of patient-related information and record-keeping processes. Further large scale studies are required to investigate national trends of poisoning and factors associated with poisoning.

  16. Person-job and person-organization fits: Co-op fits in an aerospace engineering environment

    NASA Astrophysics Data System (ADS)

    Urban, Anthony John, Jr.

    This dissertation research was a replication of a quantitative study completed by Dr. Cynthia Shantz at Wayne State University during 2003. The intent of the research was to investigate the fits of college students who participated in cooperative academic-work programs (co-ops) to employment positions within aerospace engineering. The objective of investigating person-job (P-J) and person-organization (P-O) fits was to determine if variables could be identified that indicated an individual's aptitude to complete successfully aerospace engineering standard work. Research participants were co-op employees who were surveyed during their employment to identify indications of their fits into their organization and job assignments. Dr. Shantz's research led to the thought employment success might increase when P-J and P-O fits increase. For example, reduced initial training investments and increased employee retention might result with improved P-O and P-J fits. Research data were gathered from surveys of co-ops who worked at a Connecticut aerospace engineering company. Data were collected by distributing invitations to co-ops to participate in three online surveys over a 9-11 week period. Distribution of survey invitations was accomplished through the Human Resources Department to ensure that respondent identities were maintained private. To protect anonymity and privacy further, no identifying information about individuals or the company is published. However, some demographic information was collected to ensure that correlations were based on valid and reliable data and research and analysis methods. One objective of this research was to determine if co-op characteristics could be correlated with successful employment in an aerospace engineering environment. A second objective was to determine if P-J and P-O fits vary over time as co-ops become increasing familiar with their assignments, organization, and environment. Understanding and incorporating the use P-J and P

  17. Sperm viability and gene expression in honey bee queens (Apis mellifera) following exposure to the neonicotinoid insecticide Imidacloprid and the organophosphate Acaricide Coumaphos

    USDA-ARS?s Scientific Manuscript database

    Honey bee population declines are a global concern. Numerous factors appear to cause the decline including parasites, pathogens, malnutrition and pesticides. Residues of the organophosphate acaricide coumaphos and the neonicotinoid insecticide imidacloprid, widely used to combat Varroa mites and for...

  18. Tailoring a ConOps for NASA LSP Integrated Operations

    NASA Technical Reports Server (NTRS)

    Owens, Skip Clark V., III

    2017-01-01

    An integral part of the Systems Engineering process is the creation of a Concept of Operations (ConOps) for a given system, with the ConOps initially established early in the system design process and evolved as the system definition and design matures. As Integration Engineers in NASA's Launch Services Program (LSP) at Kennedy Space Center (KSC), our job is to manage the interface requirements for all the robotic space missions that come to our Program for a Launch Service. LSP procures and manages a launch service from one of our many commercial Launch Vehicle Contractors (LVCs) and these commercial companies are then responsible for developing the Interface Control Document (ICD), the verification of the requirements in that document, and all the services pertaining to integrating the spacecraft and launching it into orbit. However, one of the systems engineering tools that have not been employed within LSP to date is a Concept of Operations. The goal of this paper is to research the format and content that goes into these various aerospace industry ConOps and tailor the format and content into template form, so the template may be used as an engineering tool for spacecraft integration with future LSP procured launch services. This tailoring effort was performed as the authors final Masters Project in the Spring of 2016 for the Stevens Institute of Technology and modified for publication with INCOSE (Owens, 2016).

  19. Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Katz, Francine S.; Pecic, Stevan; Tran, Timothy H.

    Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups—Mannich phenols and general bases—that are capable of reactivating OPC-inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data,more » significantly broaden the available approaches for reactivation of AChE.« less

  20. Operational trace gas column observations from GOME-2 on MetOp

    NASA Astrophysics Data System (ADS)

    Valks, Pieter; Hao, Nan; Pinardi, Gaia; Hedelt, Pascal; Liu, Song; Van Roozendael, Michel; De Smedt, Isabelle; Theys, Nicolas; Koukouli, MariLiza; Balis, Dimitris

    2017-04-01

    This contribution focuses on the operational GOME-2 trace gas column products developed in the framework of EUMETSAT's Satellite Application Facility on Atmospheric Composition Monitoring (AC-SAF). We present an overview of the retrieval algorithms for ozone, OClO, NO2, SO2 and formaldehyde, and we show examples of various applications such as air quality and climate monitoring, using observations from the GOME-2 instruments on MetOp-A and MetOp-B. Total ozone and the minor trace gas columns from GOME-2 are retrieved with the latest version 4.8 of the GOME Data Processor (GDP), which uses an optimized Differential Optical Absorption Spectroscopy (DOAS) algorithm, with air mass factor conversions based on the LIDORT model. Improved total and tropospheric NO2 columns are retrieved in the visible wavelength region between 425 and 497 nm. SO2 emissions from volcanic and anthropogenic sources can be measured by GOME-2 using the UV wavelength region around 320 nm. For formaldehyde, an optimal DOAS fitting window around 335 nm has been determined for GOME-2. The GOME-2 trace gas columns have reached the operational EUMETSAT product status, and are available to the users in near real time (within two hours after sensing by GOME-2). The use of trace gas observations from the GOME-2 instruments on MetOp-A and MetOp-B for air quality purposed will be illustrated, e.g. for South-East Asia and Europe. Furthermore, comparisons of the GOME-2 satellite observations with ground-based measurements will be shown. Finally, the use of GOME-2 trace-gas column data in the Copernicus Atmosphere Monitoring Service (CAMS) will be presented.

  1. Synergy between Repellents and Organophosphates on Bed Nets: Efficacy and Behavioural Response of Natural Free-Flying An. gambiae Mosquitoes

    PubMed Central

    Pennetier, Cédric; Costantini, Carlo; Corbel, Vincent; Licciardi, Séverine; Dabiré, Roch K.; Lapied, Bruno; Chandre, Fabrice; Hougard, Jean-Marc

    2009-01-01

    Background Chemicals are used on bed nets in order to prevent infected bites and to kill aggressive malaria vectors. Because pyrethroid resistance has become widespread in the main malaria vectors, research for alternative active ingredients becomes urgent. Mixing a repellent and a non-pyrethroid insecticide seemed to be a promising tool as mixtures in the laboratory showed the same features as pyrethroids. Methodology/Principal Findings We present here the results of two trials run against free-flying Anopheles gambiae populations comparing the effects of two insect repellents (either DEET or KBR 3023, also known as icaridin) and an organophosphate insecticide at low-doses (pirimiphos-methyl, PM) used alone and in combination on bed nets. We showed that mixtures of PM and the repellents induced higher exophily, blood feeding inhibition and mortality among wild susceptible and resistant malaria vectors than compounds used alone. Nevertheless the synergistic interactions are only involved in the high mortality induced by the two mixtures. Conclusion These field trials argue in favour of the strategy of mixing repellent and organophosphate on bed nets to better control resistant malaria vectors. PMID:19936249

  2. Parents' experience of undertaking an intensive cognitive orientation to daily occupational performance (CO-OP) group for children with cerebral palsy.

    PubMed

    Jackman, Michelle; Novak, Iona; Lannin, Natasha; Froude, Elspeth

    2017-05-01

    The purpose of this study was to explore the experience of parents of children with cerebral palsy (CP) who participated in an intensive cognitive orientation to daily occupational performance (CO-OP) group program addressing child chosen goals. Participants were six parents of children with CP who participated in a CO-OP upper limb task-specific training program. Parents participated in semi-structured interviews conducted via phone. A grounded theory approach was used. Interviews were transcribed verbatim and coded to identify categories and overarching themes of the parent experience of CO-OP. The theory of CO-OP for children with CP was one of offering a unique and motivating learning experience for both the child and the parent, differing from other therapeutic approaches that families had previously been involved in. Five categories were identified: the unique benefits of CO-OP; the importance of intensity; the child's motivation; challenging the parent role; and the benefits and challenges of therapy within a group context. Parents felt that CO-OP was a worthwhile intervention that leads to achievement of goals involving upper limb function and had the capacity to be transferred to future goals. Intensity of therapy and a child's motivation were identified as important factors in improvements. Further studies using quantitative research methods are warranted to investigate the benefits of CO-OP for children with neurological conditions. Implications for rehabilitation The cognitive orientation to daily occupational performance (CO-OP) is a promising upper limb cognitive motor training intervention for children with cerebral palsy. In a small sample, parents perceived that CO-OP leads to achievement of upper limb goals. Intensity of therapy, the child's motivation and the parents' ability to "step-back" were identified as important to the success of CO-OP.

  3. Upgrades of edge, divertor and scrape-off layer diagnostics of W7-X for OP1.2

    DOE PAGES

    Hathiramani, D.; Ali, A.; Anda, G.; ...

    2018-02-07

    In this work, Wendelstein 7-X (W7-X) is the world’s largest superconducting nuclear fusion experiment of the optimized stellarator type. In the first Operation Phase (OP1.1) helium and hydrogen plasmas were studied in limiter configuration. The heating energy was limited to 4 MJ and the main purpose of that campaign was the integral commissioning of the machine and diagnostics, which was achieved very successfully. Already from the beginning a comprehensive set of diagnostics was available to study the plasma. On the path towards high-power, high-performance plasmas, W7-X will be stepwise upgraded from an inertially cooled (OP1.2, limited to 80 MJ) tomore » an actively cooled island divertor (OP2, 10 MW steady-state plasma operation). The machine is prepared for OP1.2 with 10 inertially cooled divertor units, and the experimental campaign has started recently.The paper describes a subset of diagnostics which will be available for OP1.2 to study the plasma edge, divertor and scrape-off layer physics including those already available for OP1.1, plus modifications, upgrades and new systems. In conclusion, the focus of this summary will be on technical and engineering aspects, like feasibility and assembly but also on reliability, thermal loads and shielding against magnetic fields.« less

  4. Subacute poisoning with phosalone, an organophosphate insecticide.

    PubMed Central

    O'Malley, M. A.; McCurdy, S. A.

    1990-01-01

    An illness characterized by weakness, dizziness, and gastrointestinal symtoms was identified among a crew of 30 migrant field-workers employed by a grape grower in Madera County, California, during August 1987. The onset of symptoms occurred between August 24 and August 30 and a median of 9 days from the date of first employment. The first crew member sought medical treatment on August 26, and 10 crew members were admitted to hospital between August 27 and August 30. For most workers, gastrointestinal and constitutional symptoms resolved shortly after admission, but 4 patients had episodes of severe sinus bradycardia persisting for several days. On the day of admission, transient atrioventricular dissociation developed in 2 persons. Interviews with 16 crew members not admitted to the hospital identified only 1 additional worker ill with gastrointestinal symptoms, but all 16 had moderate to severe inhibition of both plasma and red blood cell cholinesterase. Four other workers who were tested but not interviewed also had cholinesterase depression. The crew had had exposure since August 19 to the organophosphate insecticide phosalone, which was last applied to the vineyard on July 21, or 29 days earlier. Although this is the first report unequivocally linking phosalone to field-worker poisoning, the delayed onset and nonspecific nature of the symptoms associated with subacute poisoning may have hindered the recognition of previous similar episodes. Images PMID:2293466

  5. Reactivation of organophosphate-inhibited human acetylcholinesterase by isonitrosoacetone (MINA): a kinetic analysis.

    PubMed

    Worek, Franz; Thiermann, Horst

    2011-11-15

    Treatment of poisoning by highly toxic organophosphorus compounds (OP) with atropine and an acetylcholinesterase (AChE) reactivator (oxime) is of limited effectiveness in case of different nerve agents and pesticides. One challenge is the reactivation of OP-inhibited brain AChE which shows inadequate success with charged pyridinium oximes. Recent studies with high doses of the tertiary oxime isonitrosoacetone (MINA) indicated a beneficial effect on central and peripheral AChE and on survival in nerve agent poisoned guinea pigs. Now, an in vitro study was performed to determine the reactivation kinetics of MINA with tabun-, sarin-, cyclosarin-, VX- and paraoxon-inhibited human AChE. MINA showed an exceptionally low affinity to inhibited AChE but, with the exception of tabun-inhibited AChE, a moderate to high reactivity. In comparison to the pyridinium oximes obidoxime, 2-PAM and HI-6 the affinity and reactivity of MINA was in most cases lower and in relation to the most effective reactivators, the second order reactivation constant of MINA was 500 to 3400-fold lower. Hence, high in vivo MINA concentrations would be necessary to achieve at least partial reactivation. This assumption corresponds to in vivo data showing a dose-dependent effect on reactivation and survival in animals. In view, of the toxic potential of MINA in animals human studies would be necessary to determine the tolerability and pharmacokinetics of MINA in order to enable a proper assessment of the value of this oxime as an antidote in OP poisoning. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

    PubMed Central

    Hulse, Elspeth J.; Davies, James O. J.; Simpson, A. John; Sciuto, Alfred M.

    2014-01-01

    Organophosphorus (OP) compound poisoning is a major global public health problem. Acute OP insecticide self-poisoning kills over 200,000 people every year, the majority from self-harm in rural Asia. Highly toxic OP nerve agents (e.g., sarin) are a significant current terrorist threat, as shown by attacks in Damascus during 2013. These anticholinesterase compounds are classically considered to cause an acute cholinergic syndrome with decreased consciousness, respiratory failure, and, in the case of insecticides, a delayed intermediate syndrome that requires prolonged ventilation. Acute respiratory failure, by central and peripheral mechanisms, is the primary cause of death in most cases. However, preclinical and clinical research over the last two decades has indicated a more complex picture of respiratory complications after OP insecticide poisoning, including onset of delayed neuromuscular junction dysfunction during the cholinergic syndrome, aspiration causing pneumonia and acute respiratory distress syndrome, and the involvement of solvents in OP toxicity. The treatment of OP poisoning has not changed over the last 50 years. However, a better understanding of the multiple respiratory complications of OP poisoning offers additional therapeutic opportunities. PMID:25419614

  7. Nanoparticle-based immunosensor with apoferritin templated metallic phosphate label for quantification of phosphorylated acetylcholinesterase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Du, Dan; Chen, Aiqiong; Xie, Yunying

    2011-05-15

    A new sandwich-like electrochemical immunosensor has been developed for quantification of organophosphorylated acetylcholinesterase (OP-AChE), an exposure biomarker of organophosphate pesticides and nerve agents. Zirconia nanoparticles (ZrO2 NPs) were anchored on a screen printed electrode (SPE) to preferably capture OP-AChE adducts by metal chelation with phospho-moieties, which was selectively recognized by lead phosphate-apoferritin labeled anti-AChE antibody (LPA-anti-AChE). The sandwich-like immunoreactions were performed among ZrO2 NPs, OP-AChE and LPA-anti-AChE to form ZrO2/OP-AChE/LPA-anti-AChE complex and the released lead ions were detected on a disposable SPE. The binding affinity was investigated by both square wave voltammetry (SWV) and quartz crystal microbalance (QCM) measurements. Themore » proposed immunosensor yielded a linear response current over a broad OP-AChE concentrations range from 0.05 nM to 10 nM, with detection limit of 0.02 nM, which has enough sensitivity for monitoring of low-dose exposure to OPs. This method avoids the drawback of unavailability of commercial OP-specific antibody as well as amplifies detection signal by using apoferritin encoded metallic phosphate nanoparticle tags. This nanoparticle-based immunosensor offers a new method for rapid, sensitive, selective and inexpensive quantification of phosphorylated adducts for monitoring of OP pesticides and nerve agents exposures.« less

  8. Examining the Effect of Co-Op Non-Employment and Rejection Sensitivity on Subjective Well-Being

    ERIC Educational Resources Information Center

    Cormier, Lauren; Drewery, David

    2017-01-01

    A growing body of literature suggests the need to better understand the subjective well-being (SWB) of students enrolled in cooperative education (co-op) programs. Some co-op students will be unsuccessful in securing employment, yet there is a scarcity of existing quantitative research outlining the impact that this will have on students,…

  9. Overview of physics goals for OP1.2a on Wendelstein 7-X

    NASA Astrophysics Data System (ADS)

    Pedersen, Thomas Sunn; W7-X Team

    2017-10-01

    Wendelstein 7-X achieved, and in many cases exceeded, the pre-defined goals for its first operation phase, OP1.1. Results include core values of Te = 8 keV, Ti = 2 keV and ne>3*1019 m-3 and confinement times of 100-150 ms. The next operation phase, OP1.2a, scheduled to start in fall 2017, features a much more elaborate set of plasma-facing components. 10 inertially cooled graphite test divertor units (TDU) have been installed, as have graphite tiles on all the heat shields and baffles. Upgrades have also been made to heating systems, diagnostics, and particle fueling systems. This will allow for significantly increased pulse lengths, heating power and plasma performance, in particular, higher plasma density, and higher ion temperatures, thereby enabling a much more detailed investigation of the W7-X optimization and significantly higher triple products than achieved in OP1.1. The robustness of the TDU allows for an aggressive exploration of divertor operation scenarios in this phase. The main goals and plans, and, if available, first results of OP1.2a will be presented. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under Grant agreement No 633053.

  10. Monitoring Indoor Exposure to Organophosphate Flame Retardants: Hand Wipes and House Dust

    PubMed Central

    Hoffman, Kate; Garantziotis, Stavros; Birnbaum, Linda S.

    2014-01-01

    Background: Organophosphate flame retardants (PFRs) are becoming popular replacements for the phased-out polybrominated diphenyl ether (PBDE) mixtures, and they are now commonly detected in indoor environments. However, little is known about human exposure to PFRs because they cannot be easily measured in blood or serum. Objectives: To investigate relationships between the home environment and internal exposure, we assessed associations between two PFRs, tris(1,3-dichloropropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP), in paired hand wipe and dust samples and concentrations of their metabolites in urine samples (n = 53). We also assessed short-term variation in urinary metabolite concentrations (n = 11 participants; n = 49 samples). Methods: Adult volunteers in North Carolina, USA, completed questionnaires and provided urine, hand wipe, and household dust samples. PFRs and PBDEs were measured in hand wipes and dust, and bis(1,3-dichloropropyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), metabolites of TDCIPP and TPHP, were measured in urine. Results: TDCIPP and TPHP were detected frequently in hand wipes and dust (> 86.8%), with geometric mean concentrations exceeding those of PBDEs. Unlike PBDEs, dust TDCIPP and TPHP levels were not associated with hand wipes. However, hand wipe levels were associated with urinary metabolites. Participants with the highest hand wipe TPHP mass, for instance, had DPHP levels 2.42 times those of participants with the lowest levels (95% CI: 1.23, 4.77). Women had higher levels of DPHP, but not BDCIPP. BDCIPP and DPHP concentrations were moderately to strongly reliable over 5 consecutive days (intraclass correlation coefficients of 0.81 and 0.51, respectively). Conclusions: PFR exposures are widespread, and hand-to-mouth contact or dermal absorption may be important pathways of exposure. Citation: Hoffman K, Garantziotis S, Birnbaum LS, Stapleton HM. 2015. Monitoring indoor exposure to organophosphate flame retardants

  11. Crossing Boundaries: Co-Op Students Relearning to Write

    ERIC Educational Resources Information Center

    Brent, Doug

    2012-01-01

    This article reviews the deeply conflicted literature on learning transfer, especially as it applies to rhetorical knowledge and skill. It then describes a study in which six students are followed through their first co-op work term to learn about which resources they draw on as they enter a new environment of professional writing. It suggests…

  12. Searching for the Cases of Acute Organophosphorus Pesticides Poisoning by JOIS

    NASA Astrophysics Data System (ADS)

    Futagami, Kojiro; Fujii, Toshiyuki; Horioka, Masayoshi; Asakura, Hajime; Fukagawa, Mitsuro

    Cholinesterase reactivator PAM (Pralidoxime) is used in the treatment of organophosphates poisoning with anticholinergic agent atropine. However, some reports demonstrated recently that PAM has inefficacy in some cases of so-called low toxicity organophosphates poisoning. So, to atempt to discuss the efficacy of PAM in clinical treatment, we searched for the case reports of these poisoning by JOIS. In this time, we compared with the specificity of each data bases and presented some examples in this on-line information retrieval.

  13. Oral health and orofacial pain in people with dementia admitted to acute hospital wards: observational cohort study.

    PubMed

    van de Rijt, Liza J M; Weijenberg, Roxane A F; Feast, Alexandra R; Vickerstaff, Victoria; Lobbezoo, Frank; Sampson, Elizabeth L

    2018-05-23

    Orofacial pain in people with dementia is difficult to detect, and often under-treated. Our aim was to investigate the prevalence of orofacial pain in people with dementia in acute hospitals in the UK. Secondary aims were to examine oral health status and explore associations between orofacial pain and oral health factors. This cross-sectional observational study was carried out in two UK hospitals. Using the Orofacial Pain Scale in Non-Verbal Individuals (OPS-NVI) to identify orofacial pain, 101 participants with dementia, admitted to acute medical wards, were observed for at least 3 min during rest and chewing. Verbal participants were then asked about presence of orofacial pain, using self-report pain scales. Finally, a brief oral assessment was performed. Orofacial pain, assessed with the OPS-NVI, was present in 11.9% (95% C.I. 5.9, 18.8) of participants at rest and 21.9% (95% C.I. 14.6, 31.3) whilst chewing. Participants who were no longer able to self-report pain were significantly more likely to experience orofacial pain. Oral health in both dentate and edentate participants was poor. Brush frequency, indication of chewing quality, consistency of the food, presence of extra-oral abnormalities, person who performed mouth care, and oral hygiene in dentate participants were significant predictors for the presence of orofacial pain. Improving oral care in acute hospital patients with dementia, particularly those who cannot self-report pain, may significantly reduce pain and suffering in this population.

  14. Overexpression, crystallization and preliminary X-ray crystallographic analysis of the phosphotriesterase from Mycobacterium tuberculosis.

    PubMed

    Zhang, Liang; Chen, Ruyi; Dong, Zhe; Li, Xin

    2013-01-01

    Organophosphates (OPs) are extremely toxic compounds that are used as insecticides or even as chemical warfare agents. Phosphotriesterases (PHPs) are responsible for the detoxification of OPs by catalysing their degradation. Almost 100 PHP structures have been solved to date, yet the crystal structure of the phosphotriesterase from Mycobacterium tuberculosis (mPHP) remains unavailable. This study reports the first crystallization of mPHP. The crystal belonged to space group C222(1), with unit-cell parameters a = 68.03, b = 149.60, c = 74.23 Å, α = β = γ = 90°. An analytical ultracentrifugation experiment suggested that mPHP exists as a dimer in solution, even though one molecule is calculated to be present in the asymmetric unit according to the structural data.

  15. Overexpression, crystallization and preliminary X-ray crystallographic analysis of the phosphotriesterase from Mycobacterium tuberculosis

    PubMed Central

    Zhang, Liang; Chen, Ruyi; Dong, Zhe; Li, Xin

    2013-01-01

    Organophosphates (OPs) are extremely toxic compounds that are used as insecticides or even as chemical warfare agents. Phosphotriesterases (PHPs) are responsible for the detoxification of OPs by catalysing their degradation. Almost 100 PHP structures have been solved to date, yet the crystal structure of the phosphotriesterase from Mycobacterium tuberculosis (mPHP) remains unavailable. This study reports the first crystallization of mPHP. The crystal belonged to space group C2221, with unit-cell parameters a = 68.03, b = 149.60, c = 74.23 Å, α = β = γ = 90°. An analytical ultracentrifugation experiment suggested that mPHP exists as a dimer in solution, even though one molecule is calculated to be present in the asymmetric unit according to the structural data. PMID:23295488

  16. [Acute inpatient conservative multimodal treatment of complex and multifactorial orthopedic diseases in the ANOA concept].

    PubMed

    Psczolla, M

    2013-10-01

    In Germany there is a clear deficit in the non-operative treatment of chronic and complex diseases and pain disorders in acute care hospitals. Only about 20 % of the treatments are carried out in orthopedic hospitals. Hospitals specialized in manual medicine have therefore formed a working group on non-operative orthopedic manual medicine acute care clinics (ANOA). The ANOA has developed a multimodal assessment procedure called the OPS 8-977 which describes the structure and process quality of multimodal and interdisciplinary diagnosis and treatment of the musculoskeletal system. Patients are treated according to clinical pathways oriented on the clinical findings. The increased duration of treatment in the German diagnosis-related groups (DRG) system is compensated for with a supplemental remuneration. Thus, complex and multifactorial orthopedic diseases and pain disorders are conservatively and appropriately treated as inpatient departments of acute care hospitals.

  17. Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp

    PubMed Central

    Gao, Shiqiang; Nagpal, Jatin; Schneider, Martin W.; Kozjak-Pavlovic, Vera; Nagel, Georg; Gottschalk, Alexander

    2015-01-01

    Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. In sensory neurons, cGMP permits signal modulation, amplification and encoding, before depolarization. Here we implement a guanylyl cyclase rhodopsin from Blastocladiella emersonii as a new optogenetic tool (BeCyclOp), enabling rapid light-triggered cGMP increase in heterologous cells (Xenopus oocytes, HEK293T cells) and in Caenorhabditis elegans. Among five different fungal CyclOps, exhibiting unusual eight transmembrane topologies and cytosolic N-termini, BeCyclOp is the superior optogenetic tool (light/dark activity ratio: 5,000; no cAMP production; turnover (20 °C) ∼17 cGMP s−1). Via co-expressed CNG channels (OLF in oocytes, TAX-2/4 in C. elegans muscle), BeCyclOp photoactivation induces a rapid conductance increase and depolarization at very low light intensities. In O2/CO2 sensory neurons of C. elegans, BeCyclOp activation evokes behavioural responses consistent with their normal sensory function. BeCyclOp therefore enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals. PMID:26345128

  18. Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp.

    PubMed

    Gao, Shiqiang; Nagpal, Jatin; Schneider, Martin W; Kozjak-Pavlovic, Vera; Nagel, Georg; Gottschalk, Alexander

    2015-09-08

    Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. In sensory neurons, cGMP permits signal modulation, amplification and encoding, before depolarization. Here we implement a guanylyl cyclase rhodopsin from Blastocladiella emersonii as a new optogenetic tool (BeCyclOp), enabling rapid light-triggered cGMP increase in heterologous cells (Xenopus oocytes, HEK293T cells) and in Caenorhabditis elegans. Among five different fungal CyclOps, exhibiting unusual eight transmembrane topologies and cytosolic N-termini, BeCyclOp is the superior optogenetic tool (light/dark activity ratio: 5,000; no cAMP production; turnover (20 °C) ∼17 cGMP s(-1)). Via co-expressed CNG channels (OLF in oocytes, TAX-2/4 in C. elegans muscle), BeCyclOp photoactivation induces a rapid conductance increase and depolarization at very low light intensities. In O2/CO2 sensory neurons of C. elegans, BeCyclOp activation evokes behavioural responses consistent with their normal sensory function. BeCyclOp therefore enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals.

  19. HI-6 assisted Catalytic Scavenging of VX by Acetylcholinesterase Choline Binding Site Mutants

    PubMed Central

    Hrvat, Nikolina Maček; Žunec, Suzana; Taylor, Palmer; Radić, Zoran; Kovarik, Zrinka

    2016-01-01

    The high toxicity of organophosphorus compounds originates from covalent inhibition of acetylcholinesterase (AChE), an essential enzyme in cholinergic neurotransmission. Poisonings that lead to life-threatening toxic manifestations require immediate treatment that combines administration of anticholinergic drugs and an aldoxime as a reactivator of AChE. An alternative approach to reduce the in vivo toxicity of OPs focuses on the use of bioscavengers against the parent organophosphate. Our previous research showed that AChE mutagenesis can enable aldoximes to substantially accelerate the reactivation of OP-enzyme conjugates, while dramatically slowing down rates of OP-conjugate dealkylation (aging). Herein, we demonstrate an efficient HI-6-assisted VX detoxification, both ex vivo in human blood and in vivo in mice by hAChE mutants modified at the choline binding site (Y337A and Y337A/F338A). The catalytic scavenging of VX in mice improved therapeutic outcomes preventing lethality and resulted in a delayed onset of toxicity symptoms. PMID:27083141

  20. Fluorescent Chemosensors for Toxic Organophosphorus Pesticides: A Review

    PubMed Central

    Obare, Sherine O.; De, Chandrima; Guo, Wen; Haywood, Tajay L.; Samuels, Tova A.; Adams, Clara P.; Masika, Noah O.; Murray, Desmond H.; Anderson, Ginger A.; Campbell, Keith; Fletcher, Kenneth

    2010-01-01

    Many organophosphorus (OP) based compounds are highly toxic and powerful inhibitors of cholinesterases that generate serious environmental and human health concerns. Organothiophosphates with a thiophosphoryl (P=S) functional group constitute a broad class of these widely used pesticides. They are related to the more reactive phosphoryl (P=O) organophosphates, which include very lethal nerve agents and chemical warfare agents, such as, VX, Soman and Sarin. Unfortunately, widespread and frequent commercial use of OP-based compounds in agricultural lands has resulted in their presence as residues in crops, livestock, and poultry products and also led to their migration into aquifers. Thus, the design of new sensors with improved analyte selectivity and sensitivity is of paramount importance in this area. Herein, we review recent advances in the development of fluorescent chemosensors for toxic OP pesticides and related compounds. We also discuss challenges and progress towards the design of future chemosensors with dual modes for signal transduction. PMID:22163587

  1. Fluorescent chemosensors for toxic organophosphorus pesticides: a review.

    PubMed

    Obare, Sherine O; De, Chandrima; Guo, Wen; Haywood, Tajay L; Samuels, Tova A; Adams, Clara P; Masika, Noah O; Murray, Desmond H; Anderson, Ginger A; Campbell, Keith; Fletcher, Kenneth

    2010-01-01

    Many organophosphorus (OP) based compounds are highly toxic and powerful inhibitors of cholinesterases that generate serious environmental and human health concerns. Organothiophosphates with a thiophosphoryl (P=S) functional group constitute a broad class of these widely used pesticides. They are related to the more reactive phosphoryl (P=O) organophosphates, which include very lethal nerve agents and chemical warfare agents, such as, VX, Soman and Sarin. Unfortunately, widespread and frequent commercial use of OP-based compounds in agricultural lands has resulted in their presence as residues in crops, livestock, and poultry products and also led to their migration into aquifers. Thus, the design of new sensors with improved analyte selectivity and sensitivity is of paramount importance in this area. Herein, we review recent advances in the development of fluorescent chemosensors for toxic OP pesticides and related compounds. We also discuss challenges and progress towards the design of future chemosensors with dual modes for signal transduction.

  2. Paraoxonase 1 and its relationship with pesticide biomarkers in indigenous Mexican farmworkers.

    PubMed

    Bernal-Hernández, Yael Yvette; Medina-Díaz, Irma Martha; Barrón-Vivanco, Briscia Socorro; Robledo-Marenco, María de Lourdes; Girón-Pérez, Manuel Iván; Pérez-Herrera, Norma Elena; Quintanilla-Vega, Betzabet; Cerda-Flores, Ricardo; Rojas-García, Aurora Elizabeth

    2014-03-01

    Biomarkers of pesticide toxicity and paraoxonase 1 (PON1) phenotype and genotypes were evaluated in indigenous Mexican farmworkers exposed mainly to organophosphate (OP) pesticides. Acetylcholinesterase, butyrylcholinesterase, and PON1 activities--arylesterase and CMPAase activities--were evaluated spectrophotometrically. PON1 55 and 192 polymorphisms were determined by real-time polymerase chain reaction. Hematological parameters were evaluated using a cytometer. Butyrylcholinesterase and arylesterase activities were lower in farmworkers, who also showed lower levels of leukocytes but higher percentages of lymphocytes when compared with the nonexposed group. Our results showed a high frequency of OP, high hydrolysis-related PON1 alleles (LL/QR and LL/RR) in the study population. An association was observed between CMPAase activity and PON1Q192R polymorphism. Our results suggest that pesticide exposure modifies biochemical and hematological biomarkers in the study population, and that the phenotype of PON1 (CMPAase) is a sensible susceptibility biomarker of OP pesticide toxicity.

  3. Microbiota-Mediated Modulation of Organophosphate Insecticide Toxicity by Species-Dependent Interactions with Lactobacilli in a Drosophila melanogaster Insect Model.

    PubMed

    Daisley, Brendan A; Trinder, Mark; McDowell, Tim W; Collins, Stephanie L; Sumarah, Mark W; Reid, Gregor

    2018-05-01

    Despite the benefits to the global food supply and agricultural economies, pesticides are believed to pose a threat to the health of both humans and wildlife. Chlorpyrifos (CP), a commonly used organophosphate insecticide, has poor target specificity and causes acute neurotoxicity in a wide range of species via the suppression of acetylcholinesterase. This effect is exacerbated 10- to 100-fold by chlorpyrifos oxon (CPO), a principal metabolite of CP. Since many animal-associated symbiont microorganisms are known to hydrolyze CP into CPO, we used a Drosophila melanogaster insect model to investigate the hypothesis that indigenous and probiotic bacteria could affect CP metabolism and toxicity. Antibiotic-treated and germfree D. melanogaster insects lived significantly longer than their conventionally reared counterparts when exposed to 10 μM CP. Drosophila melanogaster gut-derived Lactobacillus plantarum , but not Acetobacter indonesiensis , was shown to metabolize CP. Liquid chromatography tandem-mass spectrometry confirmed that the L. plantarum isolate preferentially metabolized CP into CPO when grown in CP-spiked culture medium. Further experiments showed that monoassociating germfree D. melanogaster with the L. plantarum isolate could reestablish a conventional-like sensitivity to CP. Interestingly, supplementation with the human probiotic Lactobacillus rhamnosus GG (a strain that binds but does not metabolize CP) significantly increased the survival of the CP-exposed germfree D. melanogaster This suggests strain-specific differences in CP metabolism may exist among lactobacilli and emphasizes the need for further investigation. In summary, these results suggest that (i) CPO formation by the gut microbiota can have biologically relevant consequences for the host, and (ii) probiotic lactobacilli may be beneficial in reducing in vivo CP toxicity. IMPORTANCE An understudied area of research is how the microbiota (microorganisms living in/on an animal) affects the

  4. Biomonitoring of blood cholinesterases and acylpeptide hydrolase activities in rural inhabitants exposed to pesticides in the Coquimbo Region of Chile

    PubMed Central

    Ramírez-Santana, Muriel; Farías-Gómez, Cristián; Zúñiga-Venegas, Liliana; Sandoval, Rodrigo; Roeleveld, Nel; Van der Velden, Koos; Scheepers, Paul T. J.

    2018-01-01

    In Chile, agriculture is a relevant economic activity and is concomitant with the use of pesticides to improve the yields. Acute intoxications of agricultural workers occur with some frequency and they must be reported to the surveillance system of the Ministry of Health. However the impacts of chronic and environmental pesticide exposure have been less studied. Among pesticides frequently used in Chile for insects control are organophosphates (OP) and carbamates (CB). They are inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In this study we determined the pattern of both biomarkers activity in three populations with different type of chronic exposure to OP/CB: environmentally exposed (EE), occupationally exposed (OE) and a reference group (RG) without exposure. Besides this, we also measured the activity of acylpeptide hydrolase (APEH), an enzyme involved in relevant functions in the central synapses that is also expressed in erythrocytes and previously reported to be highly inhibited by some OP. A baseline measurement was done in both exposure groups and then a second measurement was done during the spraying season. The RG was measured only once at any time of the year. Our results indicate that people under chronic OP/CB exposure showed an adaptive response through an increase of basal BChE activity. During the spray season only BChE activity was decreased in the EE and OE groups (p<0.05 and p<0.01, respectively) and the higher magnitude of BChE inhibition was observed in the EE group. The analysis of the frequencies of inhibition above 30% (biological tolerance limit declared by Chilean legislation) indicated that BChE was most frequently inhibited in the EE group (53% of the individuals displayed inhibition) and AChE in the OE group (55% of the individuals displayed AChE inhibition). APEH activity showed the highest frequency of inhibition in the EE group independent of its magnitude (64%). Our results demonstrate that the rural

  5. Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

    PubMed

    Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

    2017-02-01

    There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut-brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198-206; http://dx.doi.org/10.1289/EHP202.

  6. Creature co-op: Achieving robust remote operations with a community of low-cost robots

    NASA Technical Reports Server (NTRS)

    Bonasso, R. Peter

    1990-01-01

    The concept is advanced of carrying out space based remote missions using a cooperative of low cost robot specialists rather than monolithic, multipurpose systems. A simulation is described wherein a control architecture for such a system of specialists is being investigated. Early results show such co-ops to be robust in the face of unforeseen circumstances. Descriptions of the platforms and sensors modeled and the beacon and retriever creatures that make up the co-op are included.

  7. Effects of sublethal fenitrothion ingestion on cholinesterase inhibition, standard metabolism, thermal preference, and prey-capture ability in the Australian central bearded dragon (Pogona vitticeps, Agamidae).

    PubMed

    Bain, David; Buttemer, William A; Astheimer, Lee; Fildes, Karen; Hooper, Michael J

    2004-01-01

    The central bearded dragon (Pogona vitticeps) is a medium-sized lizard that is common in semiarid habitats in Australia and that potentially is at risk of fenitrothion exposure from use of the chemical in plague locust control. We examined the effects of single sublethal doses of this organophosphate (OP; low dose = 2.0 mg/kg; high dose = 20 mg/kg; control = vehicle alone) on lizard thermal preference, standard metabolic rate, and prey-capture ability. We also measured activities of plasma total cholinesterase (ChE) and acetylcholinesterase before and at 0, 2, 8, 24, 120, and 504 h after OP dosing. Predose plasma total ChE activity differed significantly between sexes and averaged 0.66 +/- 0.06 and 0.45 +/- 0.06 micromol/min/ml for males and females, respectively. Approximately 75% of total ChE activity was attributable to butyrylcholinesterase. Peak ChE inhibition reached 19% 2 h after OP ingestion in the low-dose group, and 68% 8 h after ingestion in high-dose animals. Neither OP doses significantly affected diurnal body temperature, standard metabolic rate, or feeding rate. Plasma total ChE levels remained substantially depressed up to 21 d after dosing in the high-dose group, making this species a useful long-term biomonitor of OP exposure in its habitat.

  8. Impairment of glutamate signaling in mouse central nervous system neurons in vitro by tri-ortho-cresyl phosphate at noncytotoxic concentrations.

    PubMed

    Hausherr, Vanessa; van Thriel, Christoph; Krug, Anne; Leist, Marcel; Schöbel, Nicole

    2014-11-01

    Occupational and environmental exposure to tri-cresyl phosphates (TCPs) may cause various types of neurotoxicity. Among the TCP isomers, tri-ortho-cresyl phosphate is a well-studied organophosphate (OP) known to cause OP-induced delayed neuropathy (OPIDN). Clinically, OPIDN is characterized by limb paralysis caused by the inhibition of neuropathy target esterase. Like other OPs, TOCP may also trigger acute toxicity by yet unknown mechanisms. Neurotoxic effects of TCPs, including TOCP, on central nervous system functions have not been studied in depth, and such non-OPIDN mechanisms might be related to the aerotoxic syndrome. To identify alternative mechanisms of TOCP neurotoxicity, we conducted an in vitro study using primary cortical neurons isolated from mouse embryos (E 16.5). After 24 h or 6 days in vitro (DIV), cell cultures were treated with different TOCP concentrations for 24 h. On DIV 2 and 7, we investigated three different endpoints--general cytotoxicity, neurite outgrowth, and glutamatergic signaling. At both time points, the EC50 for TOCP-induced cell death was 90 μM, however, neurite outgrowth was already significantly affected at TOCP concentrations of 10 μM. The number of cells responding to glutamate, as well as the corresponding mean response amplitudes were reduced with TOCP concentrations as low as 100 nM. For the first time, functional neurotoxicity is observed with very low TOCP concentrations, and in the absence of structural damages. Our proposed mechanism is that TOCP exposure may lead to cognitive deficits relevant in aerotoxic syndrome by inhibiting the signaling of glutamate, the most abundant excitatory neurotransmitter in the brain. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Association of Organophosphate Pesticide Exposure and Paraoxonase with Birth Outcome in Mexican-American Women

    PubMed Central

    Harley, Kim G.; Huen, Karen; Aguilar Schall, Raul; Holland, Nina T.; Bradman, Asa; Barr, Dana Boyd; Eskenazi, Brenda

    2011-01-01

    Background Epidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association. Methods The study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1192 and PON1−108) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records. Results Infants' PON1 genotype and activity were associated with birth outcome, but mothers' were not. Infants with the susceptible PON1−108TT genotype had shorter gestational age (β = −0.5 weeks, 95% Confidence Interval (CI): −0.9, 0.0) and smaller head circumference (β = −0.4 cm, 95% CI: −0.7, 0.0) than those with the PON1−108CC genotype. Infants' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1−108TT genotype (p-valueinteraction = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-valueinteraction = 0.06) and head circumference (p-valueinteraction<0.01) in infants with non-susceptible genotypes. Conclusions Infants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing

  10. Magnetic Fe3O4@TiO2 Nanoparticles-based Test Strip Immunosensing Device for Rapid Detection of Phosphorylated Butyrylcholinesterase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ge, Xiaoxiao; Zhang, Weiying; Lin, Yuehe

    2013-12-15

    An integrated magnetic nanoparticles-based test-strip immunosensing device was developed for rapid and sensitive quantification of phosphorylated butyrylcholinesterase (BChE), the biomarker of exposure to organophosphous pesticides (OP), in human plasma. In order to overcome the difficulty in scarce availability of OP-specific antibody, here magnetic Fe3O4@TiO2 nanoparticles were used and adsorbed on the test strip through a small magnet inserted in the device to capture target OP-BChE through selective binding between TiO2 and OP moiety. Further recognition was completed by horseradish peroxidase (HRP) and anti-BChE antibody (Ab) co-immobilized gold nanoparticles (GNPs). Their strong affinities among Fe3O4@TiO2, OP-BChE and HRP/Ab-GNPs were characterized bymore » quartz crystal microbalance (QCM), surface plasmon resonance (SPR) and square wave voltammetry (SWV) measurements. After cutting off from test strip, the resulted immunocomplex (HRP/Ab-GNPs/OP-BChE/Fe3O4@TiO2) was measured by SWV using a screen printed electrode under the test zone. Greatly enhanced sensitivity was achieved by introduction of GNPs to link enzyme and antibody at high ratio, which amplifies electrocatalytic signal significantly. Moreover, the use of test strip for fast immunoreactions reduces analytical time remarkably. Coupling with a portable electrochemical detector, the integrated device with advanced nanotechnology displays great promise for sensitive, rapid and in-filed on-site evaluation of OP poisoning.« less

  11. Cholinesterase activity of muscle tissue from freshwater fishes: characterization and sensitivity analysis to the organophosphate methyl-paraoxon.

    PubMed

    Lopes, Renato Matos; Filho, Moacelio Veranio Silva; de Salles, João Bosco; Bastos, Vera Lúcia Freire Cunha; Bastos, Jayme Cunha

    2014-06-01

    The biochemical characterization of cholinesterases (ChE) from different teleost species has been a critical step in ensuring the proper use of ChE activity levels as biomarkers in environmental monitoring programs. In the present study, ChE from Oreochromis niloticus, Piaractus mesopotamicus, Leporinus macrocephalus, and Prochilodus lineatus was biochemically characterized by specific substrates and inhibitors. Moreover, muscle tissue ChE sensitivity to the organophosphate pesticide methyl-paraoxon was evaluated by determining the inhibition kinetic constants for its progressive irreversible inhibition by methyl-paraoxon as well as the 50% inhibitory concentration (IC50) for 30 min for each species. The present results indicate that acetylcholinesterase (AChE) must be present in the muscle from P. mesopotamicus, L. macrocephalus, and P. lineatus and that O. niloticus possesses an atypical cholinesterase or AChE and butyrylcholinesterase (BChE). Furthermore, there is a large difference regarding the sensitivity of these enzymes to methyl-paraoxon. The determined IC50 values for 30 min were 70 nM (O. niloticus), 258 nM (P. lineatus), 319 nM (L. macrocephalus), and 1578 nM (P. mesopotamicus). The results of the present study also indicate that the use of efficient methods for extracting these enzymes, their kinetic characterization, and determination of sensitivity differences between AChE and BChE to organophosphate compounds are essential for the determination of accurate ChE activity levels for environmental monitoring programs. © 2014 SETAC.

  12. Organophosphate and carbamate insecticides in agricultural waters and cholinesterase (ChE) inhibition in common carp (Cyprinus carpio)

    USGS Publications Warehouse

    Gruber, S.J.; Munn, M.D.

    1998-01-01

    Cholinesterase (ChE) activity was used as a biomarker for assessing exposure of common carp (Cyprinus carpio) to organophosphate and carbamate insecticides from irrigated agricultural waters. Carp were collected from a lake (Royal Lake) that receives most of its water from irrigation return flows and from a reference lake (Billy Clapp Lake) outside of the irrigation system. Results indicated that the mean whole-brain ChE activity of carp from Royal Lake (3.47 μmol/min/g tissue) was 34.2% less than that of carp from Billy Clapp Lake (5.27 μmol/min/g tissue) (p = 0.003). The depressed ChE activity in brain tissue of Royal Lake carp was in response to ChE-inhibiting insecticides detected in water samples in the weeks prior to tissue sampling; the most frequently detected insecticides included chlorpyrifos, azinphos-methyl, carbaryl, and ethoprop. Neither sex nor size appears to be a covariable in the analysis; ChE activity was not correlated with fish length or weight in either lake and there was no significant difference in ChE activity between the two sexes within each lake. Although organophosphate and carbamate insecticides can break down rapidly in the environment, this study suggests that in agricultural regions where insecticides are applied for extended periods of the year, nontarget aquatic biota may be exposed to high levels of ChE-inhibiting insecticides for a period of several months.

  13. Field methods to evaluate effects of pesticides on wildlife of the northwestern United States

    USGS Publications Warehouse

    Henny, C.J.

    1987-01-01

    Field .methods used to evaluate the impact of organochlorine and organophosphate pesticides on wildlife populations in the Pacific Northwest are reviewed. Five field studies, presented in a CASE HISTORY format, illustrate study designs .and thetypes of information collected. The pesticides investigated included DDT, heptachlor, endr1n, and famphur, and the species studied included the American kestrel (Falco sparverius), Canada goose (Branta canadensis}, black--crowned night-heron (Nycticorax nycticorac), and black-billed magpie (Pica pica). Wildlife biologists conducting field studies of pesticides encounter a variety of design and logistics problems. However, a number of procedures are now available to the researcher for field evaluations. The three principa1 types of insecticides (organochlorines (OC's), organophosphates (OP's) and carbamates (CB's) require different field approaches. In this paper, five field studies, conducted by my colleagues and me between 1974 and 1982, in the northwestern portion of the United States (Washington, Oregon, Idaho, and northern Nevada), are reviewed to illustrate procedures for evaluating the effects of these insecticides.on wildlife populations. Althought most OC pesticides were banned in the United States during the 1970's (.for review, see F1eming et al. 1983), we studied several OC applications, including the last major DDT spray project in 1974. Use of OP's and CB's increased during the 1970's and 1980s as the OC's were phased out.

  14. Freeze-drying of HI-6-loaded recombinant human serum albumin nanoparticles for improved storage stability.

    PubMed

    Dadparvar, Miriam; Wagner, Sylvia; Wien, Sascha; Worek, Franz; von Briesen, Hagen; Kreuter, Jörg

    2014-10-01

    Severe intoxications with organophosphates require the immediate administration of atropine in combination with acetyl cholinesterase (AChE) reactivators such as HI-6. Although this therapy regimen enables the treatment of peripheral symptoms, the blood-brain barrier (BBB) restricts the access of the hydrophilic antidotes to the central nervous system which could lead to a fatal respiratory arrest. Therefore, HI-6-loaded albumin nanoparticles were previously developed to enhance the transport across this barrier and were able to reactivate organophosphate-(OP)-inhibited AChE in an in vitro BBB model. Since HI-6 is known to be moisture-sensitive, the feasibility of freeze-drying of the HI-6-loaded nanoparticles was investigated in the present study using different cryo- and lyoprotectants at different concentrations. Trehalose and sucrose (3%, w/v)-containing formulations were superior to mannitol concerning the physicochemical parameters of the nanoparticles whereas trehalose-containing samples were subject of a prolonged storage stability study at temperatures between -20°C and +40°C for predetermined time intervals. Shelf-life computations of the freeze-dried HI-6 nanoparticle formulations revealed a shelf-life time of 18 months when stored at -20°C. The formulations' efficacy was proven in vitro by reactivation of OP-inhibited AChE after transport over a porcine brain capillary endothelial cell layer model. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Comparison of posterolateral lumbar fusion rates of Grafton Putty and OP-1 Putty in an athymic rat model.

    PubMed

    Bomback, David A; Grauer, Jonathan N; Lugo, Roberto; Troiano, Nancy; Patel, Tushar Ch; Friedlaender, Gary E

    2004-08-01

    Posterolateral lumbar spine fusions in athymic rats. To compare spine fusion rates of two different osteoinductive products. Many osteoinductive bone graft alternatives are available. Grafton (a demineralized bone matrix [DBM]) and Osteogenic Protein-1 (OP-1, an individual recombinant bone morphogenetic protein) are two such alternatives. The relative efficacy of products from these two classes has not been previously studied. The athymic rat spine fusion model has been validated and demonstrated useful to minimize inflammatory responses to xenogeneic or differentially expressed proteins such as those presented by DBMs of human etiology. Single-level intertransverse process fusions were performed in 60 athymic nude rats with 2 cc/kg of Grafton or OP-1 Putty. Half of each study group was killed at 3 weeks and half at 6 weeks. Fusion masses were assessed by radiography, manual palpation, and histology. At 3 weeks, manual palpation revealed a 13% fusion rate with Grafton and a 100% fusion rate with OP-1 (P = 0.0001). At 6 weeks, manual palpation revealed a 39% fusion rate of with Grafton and a 100% fusion rate with OP-1 (P = 0.0007). Similar fusion rates were found by histology at 3 and 6 weeks. Of note, one or two adjacent levels were fused in all of the OP-1 animals and none of the Grafton animals. Significant differences between the ability of Grafton and OP-1 to induce bone formation in an athymic rat posterolateral lumbar spine fusion model were found.

  16. Acute Anticholinesterase Pesticide Poisoning Caused a Long-Term Mortality Increase

    PubMed Central

    Huang, Hung-Sheng; Hsu, Chien-Chin; Weng, Shih-Feng; Lin, Hung-Jung; Wang, Jhi-Joung; Su, Shih-Bin; Huang, Chien-Cheng; Guo, How-Ran

    2015-01-01

    Abstract Acute anticholinesterase pesticide (organophosphate and carbamate) poisoning (ACPP) often produces severe complications, and sometimes death. We investigated the long-term mortality of patients with ACPP because it is not sufficiently understood. In this retrospective nationwide population-based cohort study, 818 patients with ACPP and 16,360 healthy comparisons from 1999 to 2010 were selected from Taiwan's National Health Insurance Research Database. They were followed until 2011. Ninety-four (11.5%) ACPP patients and 793 (4.9%) comparisons died (P < 0.01) during follow-up. The incidence rate ratios (IRRs) of death were 2.5 times higher in ACPP patients than in comparisons (P < 0.01). The risk of death was particularly high in the first month after ACPP (IRR: 92.7; 95% confidence interval [CI]: 45.0–191.0) and still high for ∼6 months (IRR: 3.8; 95% CI: 1.9–7.4). After adjusting for age, gender, selected comorbidities, geographic area, and monthly income, the hazard ratio of death for ACPP patients was still 2.4 times higher than for comparisons. Older age (≥35 years), male gender, diabetes mellitus, coronary artery disease, hypertension, stroke, mental disorder, and lower monthly income also predicted death. ACPP significantly increased long-term mortality. In addition to early follow-up after acute treatment, comorbidity control and socioeconomic assistance are needed for patients with ACPP. PMID:26222853

  17. A novel all-optical label processing for OPS networks based on multiple OOC sequences from multiple-groups OOC

    NASA Astrophysics Data System (ADS)

    Qiu, Kun; Zhang, Chongfu; Ling, Yun; Wang, Yibo

    2007-11-01

    This paper proposes an all-optical label processing scheme using multiple optical orthogonal codes sequences (MOOCS) for optical packet switching (OPS) (MOOCS-OPS) networks, for the first time to the best of our knowledge. In this scheme, the multiple optical orthogonal codes (MOOC) from multiple-groups optical orthogonal codes (MGOOC) are permuted and combined to obtain the MOOCS for the optical labels, which are used to effectively enlarge the capacity of available optical codes for optical labels. The optical label processing (OLP) schemes are reviewed and analyzed, the principles of MOOCS-based optical labels for OPS networks are given, and analyzed, then the MOOCS-OPS topology and the key realization units of the MOOCS-based optical label packets are studied in detail, respectively. The performances of this novel all-optical label processing technology are analyzed, the corresponding simulation is performed. These analysis and results show that the proposed scheme can overcome the lack of available optical orthogonal codes (OOC)-based optical labels due to the limited number of single OOC for optical label with the short code length, and indicate that the MOOCS-OPS scheme is feasible.

  18. A rapid and inexpensive bioassay to evaluate the decontamination of organophosphates.

    PubMed

    Claborn, David M; Martin-Brown, Skylar A; Sagar, Sanjay Gupta; Durham, Paul

    2012-01-01

    An inexpensive and rapid bioassay using adult red flour beetles was developed for use in assessing the decontamination of environments containing organophosphates and related chemicals. A decontamination protocol was developed which demonstrated that 2 to 3 applications of 5% bleach solution were required to obtain nearly complete decontamination of malathion. The bioassay was also used to screen common household cleaners as potential decontaminating agents, but only 5% bleach was effective at improving survival of insects on steel plates treated with 25% malathion. A toxic degradation product (malaoxon) was detected using gas chromatography/mass spectrophotometry; this toxin affected the decontamination efficacy and resulted in continued toxicity to the beetles until subsequent decontaminations. The bioassay provides evidence to support the use of red flour beetles as a sensitive, less expensive method for determining safety levels of environments contaminated with malathion and other toxins, and may have application in the study of chemical warfare agents.

  19. Exposure to sheep dip and the incidence of acute symptoms in a group of Welsh sheep farmers.

    PubMed Central

    Rees, H

    1996-01-01

    OBJECTIVES: To measure the exposure of a group of farmers to organophosphate pesticide in sheep dip, and to record the incidence of symptoms after exposure. DESIGN: A prospective study of the autumn 1992 dipping period. Working methods were assessed by questionnaire. Absorption of organophosphate pesticide was estimated before, immediately after, and six weeks after dipping by measuring plasma cholinesterase, erythrocyte cholinesterase, and dialkylphosphate urinary metabolites of organophosphates. Symptoms were recorded by questionnaire at the same time as biological monitoring. Possible confounding factors were identified by medical examination of the subjects. SETTING: Three community council electoral wards in Powys, typical of hill sheep farming areas in Wales. SUBJECTS: All (38) men engaged in sheep dipping living in the three community council electoral wards. RESULTS: 23 sheep farmers and one dipping contractor completed the study--a response rate of 63%. A sample of seven men who refused to enter the full study had similar working practices to the 24 subjects. Subjects reported inadequate handling precautions, and significant skin contamination with dip. Two men reported under diluting dip concentrate for use. Both had significant depression of erythrocyte cholinesterase after dipping. This indicated some absorption of organophosphate pesticide--but this did not reach levels usually associated with toxicity. It was not clear whether the symptoms of these two mens were caused by organophosphate exposure. Measurement of dialkylphosphate urinary metabolites in a single specimen of urine voided shortly after the end of dipping could not be correlated with individual exposure. CONCLUSIONS: Sheep dipping is strenuous and dirty work and sheep farmers find it difficult to wear personal protective equipment and avoid skin contamination with dip. In this limited study, farmers did not seem to have significant organophosphate toxicity, despite using inadequate

  20. In ovo exposure to o,p -DDE affects sexual development but not sexual differentiation in Japanese medaka (Oryzias latipes).

    USGS Publications Warehouse

    Papoulias, D.M.; Villalobos, Sergio A.; Meadows, J.; Noltie, Douglas B.; Giesy, J.P.; Tillitt, D.E.

    2003-01-01

    Despite being banned in many countries, dichlorodiphenyltrichloroethane (DDT) and its metabolites dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) continue to be found in fish tissues at concentrations of concern. Like o,p -DDT, o,p -DDE is estrogenic and is believed to exert its effects through binding to the estrogen receptor. The limited toxicologic data for o,p -DDE suggest that it decreases fecundity and fertility of fishes. We conducted an egg injection study using the d-rR strain of medaka and environmentally relevant concentrations of o,p -DDE to examine its effects on sexual differentiation and development. The gonads of exposed fish showed no evidence of sex reversal or intersex. However, other gonad abnormalities occurred in exposed individuals. Females exhibited few vitellogenic oocytes and increased atresia. Male testes appeared morphologically normal but were very small. Gonadosomatic index values for both sexes were lower for exposed fish. Our observations of abnormal female and very small male gonads after in ovo o,p -DDE exposure may be indicative of effects on early endocrine processes important for normal ovarian and testicular development.