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Sample records for acute organophosphate op

  1. Pancreatic pseudocyst after acute organophosphate poisoning.

    PubMed

    Kawabe, Ken; Ito, Tetsuhide; Arita, Yoshiyuki; Sadamoto, Yojiro; Harada, Naohiko; Yamaguchi, Koji; Tanaka, Masao; Nakano, Itsuro; Nawata, Hajime; Takayanagi, Ryoichi

    2006-04-01

    Acute organophosphate poisoning (OP) shows several severe clinical symptoms due to its strong blocking effect on cholinesterase. Acute pancreatitis is one of the complications associated with acute OP, but this association still may not be widely recognized. We report here the case of a 73-year-old man who had repeated abdominal pain during and after the treatment of acute OP. Hyperamylasemia and a 7-cm pseudocyst in the pancreatic tail were noted on investigations. We diagnosed pancreatic pseudocyst that likely was secondary to an episode of acute pancreatitis following acute OP. He was initially treated with a long-term intravenous hyperalimentation, protease inhibitors and octerotide, but eventually required surgical intervention, a cystgastrostomy. Acute pancreatitis and hyperamylasemia are known to be possible complications of acute OP. It is necessary to examine and assess pancreatic damage in patients with acute OP.

  2. Central respiratory failure during acute organophosphate poisoning.

    PubMed

    Carey, Jennifer L; Dunn, Courtney; Gaspari, Romolo J

    2013-11-01

    Organophosphate (OP) pesticide poisoning is a global health problem with over 250,000 deaths per year. OPs affect neuronal signaling through acetylcholine (Ach) neurotransmission via inhibition of acetylcholinesterase (AChE), leading to accumulation of Ach at the synaptic cleft and excessive stimulation at post-synaptic receptors. Mortality due to OP agents is attributed to respiratory dysfunction, including central apnea. Cholinergic circuits are integral to many aspects of the central control of respiration, however it is unclear which mechanisms predominate during acute OP intoxication. A more complete understanding of the cholinergic aspects of both respiratory control as well as neural modification of pulmonary function is needed to better understand OP-induced respiratory dysfunction. In this article, we review the physiologic mechanisms of acute OP exposure in the context of the known cholinergic contributions to the central control of respiration. We also discuss the potential central cholinergic contributions to the known peripheral physiologic effects of OP intoxication.

  3. 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

  4. Muscular strength and vibration thresholds during two years after acute poisoning with organophosphate insecticides

    PubMed Central

    Miranda, J; McConnell, R; Wesseling, C; Cuadra, R; Delgado, E; Torres, E; Keifer, M; Lundberg, I

    2004-01-01

    Methods: This study concerns the third of a series of three examinations of hand strength and vibration thresholds in a two year period after acute OP poisoning among 48 Nicaraguan men. The first two examinations were performed at hospital discharge and seven weeks after poisoning, and the present examination two years later. Twenty eight cattle ranchers and fishermen who had never experienced pesticide poisoning were examined as controls, also three times over the two year period. The poisonings were categorised as caused by "non-neuropathic" OPs and "neuropathic" OPs, each subdivided in moderate and severe poisonings. Results: Men poisoned with OP insecticides had persistent reduced hand strength. We previously reported weakness at hospital discharge for OP poisoned in all categories that worsened seven weeks later for those severely poisoned with neuropathic OPs. Strength improved over time, but the poisoned were still weaker than controls two years after the poisoning, most noticeably among the subjects most severely poisoned with neuropathic OPs. Also, index finger and toe vibration thresholds were slightly increased at the end of the two year period, among men with OP poisonings in all categories, but patterns of onset and evolvement of impairment of vibration sensitivity were less clear than with grip and pinch strength. Conclusions: Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy. PMID:14691285

  5. Organophosphate Poisoning and Subsequent Acute Kidney Injury Risk: A Nationwide Population-Based Cohort Study.

    PubMed

    Lee, Feng-You; Chen, Wei-Kung; Lin, Cheng-Li; Lai, Ching-Yuan; Wu, Yung-Shun; Lin, I-Ching; Kao, Chia-Hung

    2015-11-01

    Small numbers of the papers have studied the association between organophosphate (OP) poisoning and the subsequent acute kidney injury (AKI). Therefore, we used the National Health Insurance Research Database (NHIRD) to study whether patients with OP poisoning are associated with a higher risk to have subsequent AKI.The retrospective cohort study comprised patients aged ≥20 years with OP poisoning and hospitalized diagnosis during 2000-2011 (N = 8924). Each OP poisoning patient was frequency-matched to 4 control patients based on age, sex, index year, and comorbidities of diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, coronary artery disease, and stroke (N = 35,696). We conducted Cox proportional hazard regression analysis to estimate the effects of OP poisoning on AKI risk.The overall incidence of AKI was higher in the patients with OP poisoning than in the controls (4.85 vs 3.47/1000 person-years). After adjustment for age, sex, comorbidity, and interaction terms, patients with OP poisoning were associated with a 6.17-fold higher risk of AKI compared with the comparison cohort. Patients with highly severe OP poisoning were associated with a substantially increased risk of AKI.The study found OP poisoning is associated with increased risk of subsequent AKI. Future studies are encouraged to evaluate whether long-term effects exist and the best guideline to prevent the continuously impaired renal function.

  6. “Toxic Pancreatitis with an Intra-Abdominal Abscess which was Caused by Organophosphate Poisoning (OP)”

    PubMed Central

    L, Venugopal; Rao V, Dharma; Rao M, Srinivas; Y, Mallikarjuna

    2013-01-01

    Organophosphate insecticides are the potent inhibitors of the acetylcholinesterase enzyme which lead to an increased acetylcholine activity, which are responsible for symptoms such as abdominal pain, diarrhoea, vomiting and hypersalivation. We are reporting on a young male with acute organophosphate poisoning, who presented with unusual complications like toxic pancreatitis with an intraabdominal abscess. PMID:23543622

  7. Fresh frozen plasma as a successful antidotal supplement in acute organophosphate poisoning.

    PubMed

    Vučinić, Slavica; Zlatković, Milica; Antonijević, Biljana; Ćurčić, Marijana; Bošković, Bogdan

    2013-06-01

    Despite improvements to intensive care management and specific pharmacological treatments (atropine, oxime, diazepam), the mortality associated with organophosphate (OP) poisoning has not substantially decreased. The objective of this examination was to describe the role of fresh frozen plasma (FFP) in acute OP poisoning. After a deliberate ingestion of malathion, a 55-year-old male suffering from miosis, somnolence, bradycardia, muscular fasciculations, rales on auscultation, respiratory insufficiency, as well as from an inhibition of red blood cell acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE), was admitted to hospital. Malathion was confirmed in a concentration of 18.01 mg L(-1). Apart from supportive measures (including mechanical ventilation for four days), antidotal treatment with atropine, oxime-pralidoxime methylsulphate (Contrathion(R)), and diazepam was administered, along with FFP. The potentially beneficial effects of FFP therapy included a prompt increase of BuChE activity (from 926 IU L(-1) to 3277 IU L(-1); reference range from 7000 IU L(-1) to 19000 IU L(-1)) and a reduction in the malathion concentration, followed by clinical recovery. Due to BuChE replacement, albumin content, and volume restitution, FFP treatment may be used as an alternative approach in patients with acute OP poisoning, especially when oximes are not available.

  8. Respiratory failure induced by acute organophosphate poisoning in rats: effects of vagotomy.

    PubMed

    Gaspari, Romolo J; Paydarfar, David

    2009-03-01

    Acute organophosphate (OP) poisoning causes respiratory failure through two mechanisms: central apnea and pulmonary dysfunction. The vagus nerve is involved in both the central control of respiratory rhythm as well as the control of pulmonary vasculature, airways and secretions. We used a rat model of acute OP poisoning with and without a surgical vagotomy to explore the role of the vagus in OP-induced respiratory failure. Dichlorvos (2,2-dichlorovinyl dimethyl phosphate) injection (100mg/kg subcutaneously, 3 x LD50) resulted in progressive hypoventilation and apnea in all animals, irrespective of whether or not the vagi were intact. However, vagotomized animals exhibited a more rapidly progressive decline in ventilation and oxygenation. Artificial mechanical ventilation initiated at onset of apnea resulted in improvement in oxygenation and arterial pressure in poisoned animals with no difference between vagus intact or vagotomized animals. Our observations suggest that vagal mechanisms have a beneficial effect during the poisoning process. We speculate that vagally mediated feedback signals from the lung to the brainstem serve as a modest protective mechanism against central respiratory depressive effects of the poison and that bulbar-generated efferent vagal signals do not cause sufficient pulmonary dysfunction to impair pulmonary gas exchange.

  9. Transient and reversible parkinsonism after acute organophosphate poisoning.

    PubMed

    Arima, Hajime; Sobue, Kazuya; So, MinHye; Morishima, Tetsuro; Ando, Hirkoshi; Katsuya, Hirotada

    2003-01-01

    Parkinsonism is a rare complication in patients with organophosphate poisoning. To date there have been two cases of transient parkinsonism after acute and severe cholinergic crisis, both of which were successfully treated using amantadine, an anti-parkinsonism drug. We report on an 81-year-old woman who was admitted for the treatment of acute severe organophosphate poisoning. Although acute cholinergic crisis was treated successfully with large doses of atropine and 2-pyridine aldoxime methiodide (PAM), extrapyramidal manifestations were noticed on hospital day 6. The neurological symptoms worsened, and the diagnosis of parkinsonism was made by a neurologist on hospital day 9. Immediately, biperiden (5mg), an anti-parkinsonism drug, was administered intravenously, and her symptoms markedly improved. From the following day, biperiden (5 mg/day) was given intramuscularly for eight days. Subsequently, neurological symptoms did not relapse, and no drugs were required. Our patient is the third case of parkinsonism developing after an acute severe cholinergic crisis and the first case successfully treated with biperiden. Patients should be carefully observed for the presence of neurological signs in this kind of poisoning. If present, an anti-parkinsonism drug should be considered.

  10. 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.

  11. Poisoning severity score, Glasgow coma scale, corrected QT interval in acute organophosphate poisoning.

    PubMed

    Akdur, Okhan; Durukan, Polat; Ozkan, Seda; Avsarogullari, Levent; Vardar, Alper; Kavalci, Cemil; Ikizceli, Ibrahim

    2010-05-01

    The aim of this study was to investigate effectiveness of the poisoning severity score (PSS), Glasgow coma scale (GCS), and corrected QT (QTc) interval in predicting outcomes in acute organophosphates (OP) poisoning. Over a period of 2 years, 62 patients with OP poisoning were admitted to emergency department (ED) of Erciyes University Medical School Hospital. The age, sex, cause of contact, compound involved, time elapsed between exposure and admission to the ED, duration of hospital stay, and cardiac manifestations at the time of presentation were recorded. GCS and poisoning severity score (PSS) was calculated for each patient. Electrocardiogram (ECG) analysis included the rate, rhythm, ST-T abnormalities, conduction defects, and measurement of PR and QT intervals. Sixty-two patients with OP poisoning presented to our ED from January 2007 to December 2008 from which 54 patients were included in the study. The mean age was 34.1 +/- 14.8 years. Of the cases, 53.7% were female. Twenty-six patients had a prolonged QTc interval. Mean PSS of men and women was 1.8 +/- 1.0. No statistically significant correlation was found between the PSS and QTc intervals of the cases. A significant correlation was determined between the GCS and PSS of grade 3 and grade 4 cases. GCS is a parameter that helps clinician to identify advanced grade OP poisoning patients in the initial assessment in the ED. However, ECG findings, such as prolonged QTc interval, are not effective in determination of short-term prognosis and show no relationship with PSS.

  12. Increased Risk of Dementia in Patients With Acute Organophosphate and Carbamate Poisoning: A Nationwide Population-Based Cohort Study.

    PubMed

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

    2015-07-01

    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.

  13. 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.

  14. Is hair analysis for dialkyl phosphate metabolites a suitable biomarker for assessing past acute exposure to organophosphate pesticides?

    PubMed

    Tsatsakis, A M; Tutudaki, M; Tzatzarakis, M N; Dawson, A; Mohamed, F; Christaki, M; Alegakis, A K

    2012-03-01

    In the present paper, the possibility to use dialkyl phosphate metabolites (DAPs) hair segmental analysis as a biomarker of past acute exposure to organophosphates is examined. Hair samples of four acute poisoning survivors were collected and segmental hair analysis was performed. The total hair samples were divided to 1 cm segments and analysed by gas chromatography-mass spectrometry (GC-MS) for the presence of four DAP metabolites, dimethyl phosphate (DMP), diethyl phosphate (DEP), diethyl thiophosphate (DETP) and diethyl dithiophosphate (DEDTP). Results were examined under the light of pesticide type and time of hair sample collection. Although DAPs were detected all along the hair shaft, higher concentrations (peaks) were detected in the segments proximate to the suicide period. It was also observed that the elevated concentrations of the present metabolites corresponded to the ones produced by the ingested parent compound. Conclusively, measurements of DAPs in the appropriate hair segments of OP-poisoned patients can be used for assessing past acute exposure to organophosphates in certain cases.

  15. Late-onset distal polyneuropathy due to acute organophosphate intoxication case report.

    PubMed

    Genel, Ferah; Arslanoğlu, Sertaç; Uran, Nedret; Doğan, Mustafa; Atlihan, Füsun

    2003-01-01

    Intoxications due to organophosphate insecticides are common in our country, since agriculture has an important place. Besides the well known acute cholinergic toxicity, these compounds may cause late-onset distal polyneuropathy occurring two to three weeks after the acute exposure. An eight-year-old boy and a 13-year-old girl admitted to the hospital with gait disturbances. Beginning 15 and 20 days, respectively, after organophosphate ingestion. Neurologic examination revealed bilateral dropped foot, absent Achilles tendon reflexes and peripheral sensory loss. Electromyography demonstrated motor weighed sensory-motor polyneuropathy with axonal degeneration significant in the distal parts of bilateral lower extremities. Biochemical, radiological findings and magnetic resonance imagings were normal. The two cases were taken under a physiotherapy program. The two cases are presented here since organophosphate poisonings are common in our country, and since late-onset polyneuropathy is not a well known clinical presentation as acute toxicity.

  16. Acute disturbance of calcium homeostasis in PC12 cells as a novel mechanism of action for (sub)micromolar concentrations of organophosphate insecticides.

    PubMed

    Meijer, Marieke; Hamers, Timo; Westerink, Remco H S

    2014-07-01

    Organophosphates (OPs) and carbamates are widely used insecticides that exert their neurotoxicity via inhibition of acetylcholine esterase (AChE) and subsequent overexcitation. OPs can induce additional neurotoxic effects at concentrations below those for inhibition of AChE, indicating other mechanisms of action are also involved. Since tight regulation of the intracellular calcium concentration ([Ca(2+)]i) is essential for proper neuronal development and function, effects of one carbamate (carbaryl) and two OPs (chlorpyrifos, parathion-ethyl) as well as their -oxon metabolites on [Ca(2+)]i were investigated. Effects of acute (20min) exposure to (mixtures of) insecticides on basal and depolarization-evoked [Ca(2+)]i were measured in fura-2-loaded PC12 cells using single-cell fluorescence microscopy. Acute exposure to chlorpyrifos and its metabolite chlorpyrifos-oxon (10μM) induced a modest increase in basal [Ca(2+)]i. More importantly, the tested OPs concentration-dependently inhibited depolarization-evoked [Ca(2+)]i. Chlorpyrifos already induced a ∼30% inhibition at 0.1μM and a 100% inhibition at 10μM (IC50=0.43μM), whereas parathion-ethyl inhibited the depolarization-evoked [Ca(2+)]i increase with ∼70% at 10μM. Interestingly, -oxon metabolites were more potent inhibitors of AChE, but were less potent inhibitors of depolarization-evoked [Ca(2+)]i compared to their parent compound (chlorpyrifos-oxon) or were even without effect (paraoxon-ethyl and -methyl). Similarly, acute exposure to carbaryl had no effect on [Ca(2+)]i. Exposure to mixtures of chlorpyrifos with its oxon-analog or with parathion-ethyl did not increase the degree of inhibition, indicating additivity does not apply. These data demonstrate that concentration-dependent inhibition of depolarization-evoked [Ca(2+)]i is a novel mechanism of action of (sub)micromolar concentrations of OPs that could partly underlie OP-induced neurotoxicity.

  17. Mania following organophosphate poisoning.

    PubMed

    Mohapatra, Satyakam; Rath, Neelmadhav

    2014-11-01

    Organophosphate poisoning is the most common poisoning in developing countries. Although the acute muscarinic and nicotinic side-effects of organophosphate poisoning are well known and easily recognized, but neuropsychiatric changes are rarely reported. We are reporting a case of a 33-year-old female who developed manic episode following acute organophosphate poisoning.

  18. Therapeutic effectiveness of sustained low-efficiency hemodialysis plus hemoperfusion and continuous hemofiltration plus hemoperfusion for acute severe organophosphate poisoning.

    PubMed

    Hu, Shou-liang; Wang, Dan; Jiang, Hong; Lei, Qing-feng; Zhu, Xiao-hua; Cheng, Jun-zhang

    2014-02-01

    There is no report on the effects of sustained low-efficiency dialysis (SLED) plus hemoperfusion (HP) (SLED + HP) in patients with acute severe organophosphate (OP) poisoning (ASOPP). This study was designed to compare the therapeutic effectiveness between SLED + HP and continuous hemofiltration (CHF) plus HP (CHF + HP) in patients with ASOPP. In order to assess the two treatment methods, 56 patients with ASOPP were divided into CHF + HP group and SLED + HP group. The biochemical indicators, in-hospital duration, hemodynamic parameters, Acute Physiology, and Chronic Health Evaluation (APACHE II) score, and survival and mortality rates were compared. In both groups after treatment, the levels of serum creatine kinase isozyme MB, creatine kinase, creatinine, glutamic-oxalacetic transaminease, and glutamate-pyruvate transaminase, and the APACHE II scores on the first, second, and seventh day decreased (P < 0.05), whereas the levels of serum acetylcholinesterase increased. The two groups showed no statistical differences in in-hospital duration, biochemical indicators, APACHE II score, hemodynamic parameters, survival rate, or the mortality rate (P > 0.05). In conclusion, SLED has similar hemodynamic stability to CHF and the two treatment methods have similar effects on ASOPP patients. More importantly, SLED plus HP is relatively economical and convenient for patients with ASOPP in clinical practice.

  19. Impacts of hypersaline acclimation on the acute toxicity of the organophosphate chlorpyrifos to salmonids.

    PubMed

    Maryoung, Lindley A; Lavado, Ramon; Schlenk, Daniel

    2014-07-01

    Acclimation to hypersaline conditions enhances the acute toxicity of certain thioether organophosphate and carbamate pesticides in some species of euryhaline fish. As the organophosphate chlorpyrifos is commonly detected in salmonid waterways, the impacts of hypersaline conditions on its toxicity were examined. In contrast to other previously examined pesticides, time to death by chlorpyrifos was more rapid in freshwater than in hypersaline water (16ppth). The median lethal time (LT50) after 100μg/L chlorpyrifos exposure was 49h (95% CI: 31-78) and 120h (95% CI: 89-162) for rainbow trout (Oncorhynchus mykiss) in freshwater and those acclimated to hypersaline conditions, respectively. Previous studies with hypersaline acclimated fish indicated induction of xenobiotic metabolizing enzymes that may detoxify chlorpyrifos. In the current study, chlorpyrifos metabolism was unaltered in liver and gill microsomes of freshwater and hypersaline acclimated fish. Acetylcholinesterase inhibition in brain and bioavailability of chlorpyrifos from the aqueous exposure media were also unchanged. In contrast, mRNA expression of neurological targets: calcium calmodulin dependent protein kinase II delta, chloride intracellular channel 4, and G protein alpha i1 were upregulated in saltwater acclimated fish, consistent with diminished neuronal signaling which may protect animals from cholinergic overload associated with acetylcholinesterase inhibition. These results indicate targets other than acetylcholinesterase may contribute to the altered toxicity of chlorpyrifos in salmonids under hypersaline conditions.

  20. Acute severe organophosphate poisoning in a child who was successfully treated with therapeutic plasma exchange, high-volume hemodiafiltration, and lipid infusion.

    PubMed

    Yesilbas, Osman; Kihtir, Hasan S; Altiti, Mohammad; Petmezci, Mey Talip; Balkaya, Seda; Bursal Duramaz, Burcu; Ersoy, Melike; Sevketoglu, Esra

    2016-10-01

    Acute severe organophosphate poisoning is a serious complication seen in developing and agricultural countries. Pralidoxime and high dose atropine are the standard treatments. There is no consensus about acute severe organophosphate poisonings that are unresponsive to pralidoxime, atropine, and supportive therapies. We report a case of acute severe organophosphate poisoning that was unresponsive to standard treatments and successfully treated with high-volume continuous venovenous hemodiafiltration and therapeutic plasma exchange combined with lipid infusion. J. Clin. Apheresis 31:467-469, 2016. © 2015 Wiley Periodicals, Inc.

  1. Spatiotemporal pattern of neuronal injury induced by DFP in rats: A model for delayed neuronal cell death following acute OP intoxication

    SciTech Connect

    Li Yonggang; Lein, Pamela J.; Liu Cuimei; Bruun, Donald A.; Tewolde, Teclemichael; Ford, Gregory; Ford, Byron D.

    2011-06-15

    Organophosphate (OP) neurotoxins cause acute cholinergic toxicity and seizures resulting in delayed brain damage and persistent neurological symptoms. Testing novel strategies for protecting against delayed effects of acute OP intoxication has been hampered by the lack of appropriate animal models. In this study, we characterize the spatiotemporal pattern of cellular injury after acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats received pyridostigmine (0.1 mg/kg, im) and atropine methylnitrate (20 mg/kg, im) prior to DFP (9 mg/kg, ip) administration. All DFP-treated animals exhibited moderate to severe seizures within minutes after DFP injection but survived up to 72 h. AChE activity was significantly depressed in the cortex, hippocampus, subcortical brain tissue and cerebellum at 1 h post-DFP injection and this inhibition persisted for up to 72 h. Analysis of neuronal injury by Fluoro-Jade B (FJB) labeling revealed delayed neuronal cell death in the hippocampus, cortex, amygdala and thalamus, but not the cerebellum, starting at 4 h and persisting until 72 h after DFP treatment, although temporal profiles varied between brain regions. At 24 h post-DFP injection, the pattern of FJB labeling corresponded to TUNEL staining in most brain regions, and FJB-positive cells displayed reduced NeuN immunoreactivity but were not immunopositive for astrocytic (GFAP), oligodendroglial (O4) or macrophage/microglial (ED1) markers, demonstrating that DFP causes a region-specific delayed neuronal injury mediated in part by apoptosis. These findings indicate the feasibility of this model for testing neuroprotective strategies, and provide insight regarding therapeutic windows for effective pharmacological intervention following acute OP intoxication. - Research Highlights: > DFP induced neuronal FJB labeling starting at 4-8 h after treatment > The pattern of DFP-induced FJB labeling closely corresponded to TUNEL staining > FJB

  2. Organophosphate intermediate syndrome with neurological complications of extrapyramidal symptoms in clinical practice

    PubMed Central

    Detweiler, Mark B.

    2014-01-01

    Organophosphates (OPs) are ubiquitous in the world as domestic and industrial agricultural insecticides. Intentional poisoning as suicides attempts are clinical phenomena seen in emergency departments and clinics in agricultural areas. Intermediate syndrome with the neurological complication of extra pyramidal symptoms following acute OP ingestion may occur in pediatric and adult cases. While death is the most serious consequence of toxic OP doses, low levels of exposure and nonfatal doses may disrupt the neurobehavioral development of fetuses and children in addition to bring linked to testicular cancer and male and female infertility. These are disturbing. Chronic and acute toxicity from OPs are barriers to the health of our present and future generations. Symptoms and treatment of acute and chronic OP exposure are briefly referenced with inclusion of the intermediate syndrome. Suggestions for local and systemic reduction of the acute and long term consequences of OP ingestion are opined. PMID:25002781

  3. Role of Magnetic Resonance Imaging in Diagnosing Neurological Complications in Intermediate Syndrome of Organophosphate Poisoning

    PubMed Central

    Ravikanth, Reddy

    2017-01-01

    Organophosphate poisoning (OP) is a very common mode of suicide in rural and urban areas due to the wide availability of pesticides. The identification of OP and timely referral for appropriate supportive care can be lifesaving. Injury to the central nervous system is a serious entity in acute OP. Application of modern imaging techniques like diffusion weighted imaging increases the diagnostic rate of brain injury in the early period and can provide evidence for medical treatment. We present the imaging features in the intermediate syndrome of OP. PMID:28250609

  4. 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

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

    PubMed

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

  6. Much caution does no harm! Organophosphate poisoning often causes pancreatitis.

    PubMed

    Yoshida, Shozo; Okada, Hideshi; Nakano, Shiho; Shirai, Kunihiro; Yuhara, Toshiyuki; Kojima, Hiromasa; Doi, Tomoaki; Kato, Hisaaki; Suzuki, Kodai; Morishita, Kentaro; Murakami, Eiji; Ushikoshi, Hiroaki; Toyoda, Izumi; Ogura, Shinji

    2015-01-01

    Organophosphate poisoning (OP) results in various poisoning symptoms due to its strong inhibitory effect on cholinesterase. One of the occasional complications of OP is pancreatitis. A 62-year-old woman drank alcohol and went home at midnight. After she quarreled with her husband and drank 100 ml of malathion, a parasympathomimetic organophosphate that binds irreversibly to cholinesterase, she was transported to our hospital in an ambulance. On admission, activated charcoal, magnesium citrate, and pralidoxime methiodide (PAM) were used for decontamination after gastric lavage. Abdominal computed tomography detected edema of the small intestine and colon with doubtful bowel ischemia, and acute pancreatitis was suspected. Arterial blood gas analysis revealed severe lactic acidosis. The Ranson score was 6 and the APACHE II (Acute Physiology and Chronic Health Evaluation) score was 14. Based on these findings, severe acute pancreatitis was diagnosed. One day after admission, hemodiafiltration (HDF) was started for the treatment of acute pancreatitis. On the third hospital day, OP symptoms were exacerbated, with muscarinic manifestations including bradycardia and hypersalivation and decreased plasma cholinesterase activity. Atropine was given and the symptoms improved. The patient's general condition including hemodynamic status improved. Pancreatitis was attenuated by 5 days of HDF. Ultimately, it took 14 days for acute pancreatitis to improve, and the patient discharged on hospital day 32. Generally, acute pancreatitis associated with OP is mild. In fact, one previous report showed that the influence of organophosphates on the pancreas disappears in approximately 72 hours, and complicated acute pancreatitis often improves in 4-5 days. However, it was necessary to treat pancreatitis for more than 2 weeks in this case. Therefore, organophosphate-associated pancreatitis due to malathion is more severe. Although OP sometime causes severe necrotic pancreatitis or

  7. Is there a relationship between the blood cholinesterase and QTc interval in the patients with acute organophosphate poisoning?

    PubMed

    Baydin, A; Aygun, D; Yazici, M; Karatas, A; Deniz, T; Yardan, T

    2007-06-01

    Organophosphates cause poisoning as a result of the excessive accumulation of acetylcholine at the cholinergic synapses due to inhibition of acetylcholinesterase (ChE). In the literature, it has been reported that there have been electrocardiographic abnormalities, including QT-interval prolongation in most patients with acute organophosphate poisoning (OPP), and a relation between blood ChE level and clinical severity in acute OPP. The aim of this study is to assess the relationship between blood ChE level and QTc interval in the patients with acute OPP. This retrospective study consists of 20 patients admitted to the emergency intensive care unit. A total of 93 QTc interval and blood ChE measures obtained on the same day from 20 cases were compared for their correlation. There were prolonged QTc intervals in 35.4% of the ECGs. There was a negative correlation between QTc interval and blood ChE measures. In following up the patients with acute OPP, QTc interval may be useful when blood ChE levels are low and may provide complementary information concerning the severity of poisoning. However, further prospective studies, supporting the present results, are needed.

  8. Ultrastructural changes in rat thyroid tissue after acute organophosphate poisoning and effects of antidotal therapy with atropine and pralidoxime: A single-blind, ex vivo study

    PubMed Central

    Satar, Deniz; Satar, Salim; Mete, Ufuk Ozgu; Suchard, Jeffrey R.; Topal, Metin; Karakoc, Emre; Kaya, Mehmet

    2008-01-01

    Background: Organophosphate (OP) insecticides are widely used in both agricultural and landscape pest control, and the potential for human exposure to these compounds is significant. Objectives: The aims of this study were to investigate the effects of acute poisoning with the OP methamidophos and the effects of antidotal therapy with atropine and pralidoxime on rat thyroid tissue ultrastructure. Methods: In this single-blind, ex vivo study, male Wistar albino rats weighing 220 to 230 g were divided into 4 treatment groups. Group 1 received a median lethal dose of methamidophos (30 mg/kg) via oral gavage. Group 2 received saline via oral gavage and served as the control group for group 1. Group 3 received methamidophos (30 mg/kg) via oral gavage, and after 8 minutes atropine 0.05 mg/kg and pralidoxime chloride (2-FAM) (40 mg/kg) were administered intraperitoneally (IP). Atropine was titrated to reverse signs of cholinergic excess. Group 4 received saline via oral gavage followed by IP injections and served as the control for group 3. Rat thyroid tissues were examined using electron microscopy, and the histologic changes were examined by a histopathologist who was blinded to treatment. All rats were euthanized by intracardiac blood collection. The rats in groups 1 and 2 were euthanized 8 minutes after treatment. The rats in groups 3 and 4 were euthanized 96 hours after treatment. Results: Thirty-four male rats (aged 16 weeks) were included in the study. The rats were grouped accordingly: group 1 (n = 10); group 2 (n = 7); group 3 (n = 10); and group 4 (n = 7). The mean (SD) pseudocholinesterase (FCE) activity was significantly lower in the methamidophos-treated rats (group 1) compared with the corresponding control group (group 2) (32.6 [17.0] vs 579.4 [59.0] U/L, respectively; P < 0.001). PCE activity was significantly higher in rats treated with atropine and 2-PAM (group 3) (392.5 [39.4] U/L; P < 0.001) compared with those not receiving antidotal therapy (group 1

  9. Use of OpdA, an Organophosphorus (OP) Hydrolase, Prevents Lethality in an African Green Monkey Model of Acute OP Poisoning

    PubMed Central

    Jackson, Colin J; Carville, Angela; Ward, Jeanine; Mansfield, Keith; Ollis, David L.; Khurana, Tejvir; Bird, Steven B.

    2014-01-01

    Organophosphorus (OP) pesticides are a diverse class of acetylcholinesterase (AChE) inhibitors that are responsible for tremendous morbidity and mortality worldwide, killing approximately 300,000 people annually. Enzymatic hydrolysis of OPs is a potential therapy for acute poisoning. OpdA, an OP hydrolase isolated from Agrobacterium radiobacter, has been shown to decrease lethality in rodent models of OP poisoning. This study investigated the effects of OpdA on AChE activity, plasma concentrations of OP, and signs of toxicity after administration of dichlorvos to nonhuman primates. A dose of 75 mg/kg dichlorvos given orally caused apnea within 10 minutes with a progressive decrease in heart rate. Blood AChE activity decreased to zero within ten minutes. Respirations and AChE activity did not recover. The mean dichlorvos concentration rose to a peak of 0.66 μg/ml. Treated monkeys received 1.2 mg/kg OpdA iv immediately after poisoning with dichlorvos. In Opda-treated animals, heart and respiratory rates were unchanged from baseline over a 240-minute observation period. AChE activity slowly declined, but remained above 25% of baseline for the entire duration. Dichlorvos concentrations reached a mean peak of 0.19 μg/ml at 40 minutes after poisoning and decreased to a mean of 0.05 μg/ml at 240 minutes. These results show that OpdA hydrolyzes dichlorvos in an African Green Monkey model of lethal poisoning, delays AChE inhibition, and prevents lethality. PMID:24447378

  10. Organophosphate and carbamate poisoning.

    PubMed

    King, Andrew M; Aaron, Cynthia K

    2015-02-01

    Organophosphates (OPs) and carbamates have a wide variety of applications, most commonly as pesticides used to eradicate agricultural pests or control populations of disease-carrying vectors. Some OP and carbamates have therapeutic indications such as physostigmine. Certain organophosphorus compounds, known as nerve agents, have been employed in chemical warfare and terrorism incidents. Both classes inhibit acetylcholinesterase (AChE) enzymes, leading to excess acetylcholine accumulation at nerve terminals. In the setting of toxicity from either agent class, clinical syndromes result from excessive nicotinic and muscarinic neurostimulation. The toxic effects from OPs and carbamates differ with respect to reversibility, subacute, and chronic effects. Decontamination, meticulous supportive care, aggressive antimuscarinic therapy, seizure control, and administration of oximes are cornerstones of management.

  11. Coronary artery bypass grafting in a patient with organophosphate poisoning.

    PubMed

    Pieris, Rajeeva R; Fernando, Ravindra

    2015-08-30

    A 43-year-old male, with no previous history of mental illness, was diagnosed with coronary heart disease, after which he became acutely depressed and attempted suicide by ingesting an organophosphate pesticide. He was admitted to an intensive care unit and treated with pralidoxime, atropine, and oxygen. His coronary occlusion pattern required early coronary artery bypass grafting (CABG) surgery. His family, apprehensive of a repeat suicidal attempt, requested surgery be performed as soon as possible. He recovered well from the OP poisoning and was mentally fit to express informed consent 2 weeks after admission. Seventeen days after poisoning, he underwent coronary artery bypass grafting and recovered uneventfully. Six years later, he remains in excellent health. We report this case because to the best of our knowledge there is no literature regarding CABG performed soon after organophosphate poisoning.

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

    SciTech Connect

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.; Campbell, James A.; Lin, Yuehe

    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. The 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.

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

    SciTech Connect

    Hancock, Sandra; Ehrich, Marion; Hinckley, Jonathan; Pung, Thitiya; Jortner, Bernard S. . E-mail: bjortner@vt.edu

    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 with 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.

  14. Impaired mitochondrial functions in organophosphate induced delayed neuropathy in rats.

    PubMed

    Masoud, Anwar; Kiran, Ravi; Sandhir, Rajat

    2009-12-01

    Acute exposure to organophosphates induces a delayed neurodegenerative condition known as organophosphate-induced delayed neuropathy (OPIDN). The mechanism of OPIDN has not been fully understood as it does not involve cholinergic crisis. The present study has been designed to evaluate the role of mitochondrial dysfunctions in the development of OPIDN. OPIDN was induced in rats by administering acute dose of monocrotophos (MCP, 20 mg/kg body weight, orally) or dichlorvos (DDVP, 200 mg/kg body weight, subcutaneously), 15-20 min after treatment with antidotes [atropine (20 mg/kg body weight) and 2-PAM (100 mg/kg body weight) intraperitoneally]. MDA levels were observed to be higher and thiol content was lower in mitochondria from brain regions of OP exposed animals. This was accompanied by decreased activities of the mitochondrial enzymes; NADH dehydrogenase, succinate dehydrogenase, and cytochrome oxidase. In addition, mitochondrial functions assessed by MTT reduction also confirmed mitochondrial dysfunctions following development of OPIDN. The spatial long-term memory evaluated using elevated plus-maze test was observed to be deficit in OPIDN. The results suggest impaired mitochondrial functions as a mechanism involved in the development of organophosphate induced delayed neuropathy.

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

    PubMed Central

    Bao, Hang-xing; Tong, Pei-jian; Li, Cai-xia; Du, Jing; Chen, Bing-yu; Huang, Zhi-hui; Wang, Ying

    2017-01-01

    Abstract 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. PMID:28296779

  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. 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...

  18. The role of glutamate and the immune system in organophosphate-induced CNS damage.

    PubMed

    Eisenkraft, Arik; Falk, Avshalom; Finkelstein, Arseny

    2013-08-01

    Organophosphate (OP) poisoning is associated with long-lasting neurological damage, which is attributed mainly to the excessive levels of glutamate caused by the intoxication. Glutamate toxicity, however, is not specific to OP poisoning, and is linked to propagation of damage in both acute and chronic neurodegenerative conditions in the central nervous system (CNS). In addition to acute excitotoxic effects of glutamate, there is now a growing amount of evidence of its intricate immunomodulatory effects in the brain, involving both the innate and the adaptive immune systems. Moreover, it was demonstrated that immunomodulatory treatments, aimed at regulating the interaction between the resident immune cells of the brain (microglia) and the peripheral immune system, can support buffering of excessive levels of glutamate and restoration of the homeostasis. In this review, we will discuss the role of glutamate as an excitotoxic agent in the acute phase of OP poisoning, and the possible functions it may have as both a neuroprotectant and an immunomodulator in the sub-acute and chronic phases of OP poisoning. In addition, we will describe the novel immune-based neuroprotective strategies aimed at counteracting the long-term neurodegenerative effects of glutamate in the CNS.

  19. Clinical features of organophosphate poisoning: A review of different classification systems and approaches

    PubMed Central

    Peter, John Victor; Sudarsan, Thomas Isiah; Moran, John L.

    2014-01-01

    Purpose: The typical toxidrome in organophosphate (OP) poisoning comprises of the Salivation, Lacrimation, Urination, Defecation, Gastric cramps, Emesis (SLUDGE) symptoms. However, several other manifestations are described. We review the spectrum of symptoms and signs in OP poisoning as well as the different approaches to clinical features in these patients. Materials and Methods: Articles were obtained by electronic search of PubMed® between 1966 and April 2014 using the search terms organophosphorus compounds or phosphoric acid esters AND poison or poisoning AND manifestations. Results: Of the 5026 articles on OP poisoning, 2584 articles pertained to human poisoning; 452 articles focusing on clinical manifestations in human OP poisoning were retrieved for detailed evaluation. In addition to the traditional approach of symptoms and signs of OP poisoning as peripheral (muscarinic, nicotinic) and central nervous system receptor stimulation, symptoms were alternatively approached using a time-based classification. In this, symptom onset was categorized as acute (within 24-h), delayed (24-h to 2-week) or late (beyond 2-week). Although most symptoms occur with minutes or hours following acute exposure, delayed onset symptoms occurring after a period of minimal or mild symptoms, may impact treatment and timing of the discharge following acute exposure. Symptoms and signs were also viewed as an organ specific as cardiovascular, respiratory or neurological manifestations. An organ specific approach enables focused management of individual organ dysfunction that may vary with different OP compounds. Conclusions: Different approaches to the symptoms and signs in OP poisoning may better our understanding of the underlying mechanism that in turn may assist with the management of acutely poisoned patients. PMID:25425841

  20. Cytotoxicity of organophosphate anticholinesterases.

    PubMed

    Cao, C J; Mioduszewski, R J; Menking, D E; Valdes, J J; Katz, E J; Eldefrawi, M E; Eldefrawi, A T

    1999-10-01

    Organophosphate (OP) anticholinesterases were found to modulate metabolic activities of human neuroblastoma cells and hepatocytes, which was detectable by the Cytosensor microphysiometer. The nerve gas ethyl-S-2-diisopropylaminoethyl methylphosphorothiolate (VX), at 10 microM, produced significant reduction in cell metabolism within 2 min, as measured by changes in the acidification rate of the medium. The reduction was dose- and time-dependent and irreversible after 4 h of exposure. Two alkaline degradation products of VX produced no cytotoxicity. Exposure for 24 h to 3 microM VX caused 36% and 94% irreversible loss of metabolism in hepatocytes and neuroblastoma cells, respectively. The insecticides parathion and chlorpyrifos stimulated hepatocyte metabolism but inhibited neuroblastoma cells. Their oxons were more active. Exposure of neuroblastoma cells for 4 h to VX, parathion, paraoxon, diisopropylfluorophosphate or chlorpyrifos gave an LC50 of 65, 775, 640, 340, or 672 microM, respectively, whereas 24 h gave an LC50 of 0.7, 3.7, 2.5, 29, and 31 microM, respectively. Preincubation of hepatocytes with phenobarbital enhanced their response to parathion and VX due to metabolic bioactivation. Atropine partially blocked the effects of VX and paraoxon on both cell types, which suggests the involvement of a muscarinic receptor as the target for cytotoxicity. There was no correlation between OP in vivo neurotoxicity and in vitro cytotoxicity. It is suggested that the former results from their cholinesterase inhibition, while the latter results from action on different targets and requires much higher concentrations.

  1. Biosensor System for Continuous Monitoring of Organophosphate Aerosols (Postprint)

    DTIC Science & Technology

    2007-05-01

    detection of a range of organophosphates including paraoxon, demeton-S and malathion . 15. SUBJECT TERMS enzyme immobilization; butyrylcholinesterase...for detection of a range of organophosphates including paraoxon, demeton-S and malathion . 2007 Elsevier B.V. All rights reserved. ydrol c s i e c r s...OPH ydrolyzes a range of OPs including pesticides (e.g. parathion nd malathion ) and chemical warfare agents (e.g. soman, sarin nd VX) (Dumas et al

  2. The role of serum cholinesterase activity and S100B protein in the evaluation of organophosphate poisoning.

    PubMed

    Yardan, T; Baydin, A; Acar, E; Ulger, F; Aygun, D; Duzgun, A; Nar, R

    2013-10-01

    The aim of this study was to investigate the role of serum cholinesterase (SChE) activity and S100B protein in the evaluation of patients with acute organophosphate (OP) poisoning. Patients with acute OP poisoning admitted to the emergency department were included in this cross-sectional study. Twenty healthy volunteers served as controls. The SChE activity and serum S100B were determined on admission. Patients were divided into two groups (low severity and high severity). Thirty-six patients diagnosed with acute OP poisoning were enrolled. Serum S100B concentrations were higher in patients than in the control group (p < 0.05). In the high-severity group, the SChE levels were lower and the S100Bs levels were higher than in the low-severity group. The SChE level was not different between survivors and nonsurvivors. S100B levels were higher in nonsurvivors than in survivors. According to receiver-operating characteristic curve analysis, the optimal cutoff value of serum S100B level to predict mortality was 236.5 pg/mL, with 71.4% sensitivity and 89.7% specificity. Our data suggest that initial SChE level is related to the clinical severity but not with mortality. S100B may be a useful marker in the assessment of clinical severity and prediction of mortality in acute OP poisoning.

  3. 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 ...

  4. 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

  5. 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.

  6. 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...

  7. 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...

  8. 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.

  9. Respiratory recovery following organophosphate poisoning in a rat model is suppressed by isolated hypoxia at the point of apnea.

    PubMed

    Gaspari, Romolo J; Paydarfar, David

    2012-12-16

    Normal respiratory activity (eupnea) and gasping represent different types of respiratory activity, one of which is supported by oxygen (eupnea) and the other suppressed by oxygen (gasping). There is a loss of respiratory activity post-organophosphate (OP) poisoning that returns following treatment. It is not clear if post-OP respiratory activity represents eupnea or gasping. Depending on the type of respiratory activity, oxygenation during recovery from OP poisoning may have the potential to either support or suppress respiratory activity. We hypothesize that respiratory recovery following OP-induced central apnea represents a resumption of eupnea and is supported by oxygenation. We used an animal model of acute OP poisoning with detailed physiologic recordings. Animals were poisoned with dichlorvos and allowed to recover during a period of mechanical ventilation. Two experimental models were analyzed: (1) animals supported with 100% oxygen and (2) animals supported with a normoxic gas mixture titrated to a PaO(2) of 115 mmHg. Rats in this study demonstrated breathing that resumes spontaneously following OP-induced apnea with characteristics of both eupnea and gasping. The post-OP respiratory activity was suppressed by hypoxia, a characteristic of eupneic respiration and not gasping respiration. However, the respiratory rate during post-apneic breathing corresponded more closely to gasping. Analysis of phrenic nerve discharge activity was distinct from both eupnea and gasping, with peak inspiratory and post-inspiratory discharge activities significantly reduced compared to both eupnea and gasping. In summary, in this animal model post-apneic breathing distinct from eupnea and gasping that emerges following prolonged OP-induced central apnea is suppressed by hypoxia.

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

    SciTech Connect

    Abdollahi, Mohammad 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 knowledge 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.

  11. 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...

  12. Serial analysis of gene expression in Rhipcephalus (Boophilus) microplus following organophoosphate treatment of larvae from organophosphate resistant and susceptible strains.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Organophosphate resistant and susceptible tick larvae from laboratory strains of the southern cattle tick, Rhipicephalus (Boophilus) microplus were exposed to low doses of the organophosphate (OP) acaricide, coumaphos. Serial analysis of gene expression (SAGE) was used to analyze differential gene e...

  13. Organophosphate-induced delayed polyneuropathy.

    PubMed

    Lotti, Marcello; Moretto, Angelo

    2005-01-01

    Organophosphate-induced delayed polyneuropathy (OPIDP) is a rare toxicity resulting from exposure to certain organophosphorus (OP) esters. It is characterised by distal degeneration of some axons of both the peripheral and central nervous systems occurring 1-4 weeks after single or short-term exposures. Cramping muscle pain in the lower limbs, distal numbness and paraesthesiae occur, followed by progressive weakness, depression of deep tendon reflexes in the lower limbs and, in severe cases, in the upper limbs. Signs include high-stepping gait associated with bilateral foot drop and, in severe cases, quadriplegia with foot and wrist drop as well as pyramidal signs. In time, there might be significant recovery of the peripheral nerve function but, depending on the degree of pyramidal involvement, spastic ataxia may be a permanent outcome of severe OPIDP. Human and experimental data indicate that recovery is usually complete in the young. At onset, the electrophysiological changes include reduced amplitude of the compound muscle potential, increased distal latencies and normal or slightly reduced nerve conduction velocities. The progression of the disease, usually over a few days, may lead to non-excitability of the nerve with electromyographical signs of denervation. Nerve biopsies have been performed in a few cases and showed axonal degeneration with secondary demyelination. Neuropathy target esterase (NTE) is thought to be the target of OPIDP initiation. The ratio of inhibitory powers for acetylcholinesterase and NTE represents the crucial guideline for the aetiological attribution of OP-induced peripheral neuropathy. In fact, pre-marketing toxicity testing in animals selects OP insecticides with cholinergic toxicity potential much higher than that to result in OPIDP. Therefore, OPIDP may develop only after very large exposures to insecticides, causing severe cholinergic toxicity. However, this was not the case with certain triaryl phosphates that were not used as

  14. Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery

    PubMed Central

    2013-01-01

    Background The principal toxicity of acute organophosphate (OP) pesticide poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethality—particularly through the inhibition of AChE—studies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms. Results We exposed cultures of worms in axenic, defined medium to dichlorvos under three exposure protocols. In the first, worms were exposed continuously throughout the experiment. In the second and third, the worms were exposed for either 2 or 8 h, the dichlorvos was washed out of the culture, and the worms were allowed to recover. We then analyzed gene expression using whole genome microarrays from RNA obtained from worms sampled at multiple time points throughout the exposure. The worms showed a time-dependent increase in the expression of genes involved in stress responses. Early in the exposure, the predominant effect was on metabolic processes, while at later times, an immune-like response and cellular repair mechanisms dominated the expression pattern. Following removal of dichlorvos, the gene expression in the worms appeared to relatively rapidly return to steady-state levels. Conclusion The changes in gene expression observed in the worms following exposure to dichlorvos point towards two potential mechanisms of toxicity: inhibition of AChE and mitochondrial disruption. PMID:23631360

  15. Quantitative structure-activity relationship of organophosphate compounds based on molecular interaction fields descriptors.

    PubMed

    Zhao, Jinsong; Yu, Shuxia

    2013-03-01

    By using multi-block partial least-squares (MBPLS) method, quantitative structure-activity relationship (QSAR) between 35 organophosphate compounds (OP) and their 24h acute toxicities towards the housefly (Musca nebulo L.) was built on the molecular interaction fields (MIF) descriptors, which were obtained with O, N and DRY as probes, and then normalised with block unscaled weights (BUW) technique. The best QSAR model had 8 principal components, with the coefficient of determination R(2)=0.995 and that of leave-one-out cross-validation Q(2)=0.865, and the corresponding standard deviation of error 0.076 and 0.361, respectively. Block importance in the prediction (BIP) for O, N and DRY probe were 1.030, 0.962 and 1.007, respectively. Contour map of variable coefficients showed that hydrogen bonding between the O atom in PO and the NH groups in acetylcholinesterase (AChE) played an important role in the interaction between OP and AChE. Meanwhile, the hydrophobicity of OP also had significant contribution. QSAR based on the MIF descriptors could be a potential means to interpret the mechanisms of ligand-receptor interaction when the receptor was well known.

  16. Central nervous system function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study

    PubMed Central

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

    2011-01-01

    Acute organophosphate (OP) pesticide exposure is associated with adverse central nervous system (CNS) outcomes, however, little is known about the neurotoxicity of chronic exposures that do not result in acute poisoning. To examine associations between long-term pesticide use and CNS function, neurobehavioral (NB) tests were administered to licensed pesticide applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. Between 2006 and 2008, 701 male participants completed nine NB tests to assess memory, motor speed and coordination, sustained attention, verbal learning and visual scanning and processing. Data on ever-use and lifetime days of use of 16 OP pesticides were obtained from AHS interviews conducted before testing between 1993 and 2007 and during the NB visit. The mean age of participants was 61 years (SD = 12). Associations between pesticide use and NB test performance were estimated with linear regression controlling for age and outcome-specific covariates. NB test performance was associated with lifetime days of use of some pesticides. Ethoprop was significantly associated with reduced performance on a test of motor speed and visual scanning. Malathion was significantly associated with poor performance on a test of visual scanning and processing. Conversely, we observed significantly better test performance for five OP pesticides. Specifically, chlorpyrifos, coumaphos, parathion, phorate, and tetrachlorvinphos were associated with better verbal learning and memory; coumaphos was associated with better performance on a test of motor speed and visual scanning; and parathion was associated with better performance on a test of sustained attention. Several associations varied by state. Overall, our results do not provide strong evidence that long-term OP pesticide use is associated with adverse CNS-associated NB test performance among this older sample of pesticide applicators. Potential reasons for these mostly null associations

  17. Sudden bilateral hearing loss after organophosphate inhalation.

    PubMed

    Dundar, Mehmet Akif; Derin, Serhan; Aricigil, Mitat; Eryilmaz, Mehmet Akif

    2016-12-01

    Sudden bilateral hearing loss are seen rarely and the toxic substance exposure constitutes a small part of etiology. A Fifty-eight-year-old woman admitted to our clinic with sudden bilateral hearing loss shortly after chlorpyrifos-ethyl exposure. Otolaryngologic examination findings were normal. The patient had 40 dB sensorineural hearing loss (SNHL) on the right ear and 48 dB SNHL on the left ear. Additional diagnostic tests were normal. The conventional treatment for sudden hearing loss was performed. On the second week following organophosphate (OP) exposure the patient's hearing loss almost completely resolved. OP's are heavily used in agriculture and should be taken into consideration as an etiologic factor in sudden hearing loss.

  18. Organophosphate poisoning in the developed world - a single centre experience from here to the millennium.

    PubMed

    Hrabetz, Heidi; Thiermann, Horst; Felgenhauer, Norbert; Zilker, Thomas; Haller, Bernhard; Nährig, Jörg; Saugel, Bernd; Eyer, Florian

    2013-12-05

    Organophosphate (OP) poisoning is still associated with high morbidity and mortality rates, both in resource-poor settings and in well-developed countries. Despite numerous publications dealing with this particular poison, detailed clinical data on more severe overdoses with these agents are relatively sparsely reported. A retrospective study was consequently conducted on 33 patients with OP poisoning admitted to our intensive care unit (ICU) to provide additional data on clinical features. We included moderate to severe poisonings between 2000 and 2012 who required admission to ICU. Patients ingested dimethyl-OPs in 19 cases, diethyl-OPs in 8 cases and otherwise classified OPs in 6 cases. Death (5/33) occurred rather late and only one of these fatalities died during on-going cholinergic crisis. Of the survivors (28/33), 71% recovered fully while 29% showed predominantly neurological disabilities before being transferred to neurologic rehabilitation. Aspiration pneumonia predominated in 27/33 patients and one patient died in refractory acute respiratory distress syndrome (ARDS). The intermediate syndrome occurred twice and cardiopulmonary resuscitation had to be performed in 6/33 patients. Fatalities showed a higher Poison-severity-score, APACHE-II-score and SOFA-score on admission compared with survivors and they showed significantly longer QTc-time in the ECG, lower systolic blood pressure and heart rate, a lower pH and a lower base excess on admission. Patients with diethyl-OPs required intubation significantly earlier and showed lower and more sustained inhibited activity of the plasma-cholinesterase on admission compared with patients ingesting dimethyl-OPs. Treatment with atropine and obidoxime was comparable between these groups and severity of poisoning, outcome, hemodynamics on admission, duration of mechanical ventilation and length of stay in the ICU did not significantly differ between the involved group of dimethyl- and diethyl-OPs. We conclude that

  19. Organophosphate vapor detection on gold electrodes using peptide nanotubes.

    PubMed

    Baker, Peter A; Goltz, Mark N; Schrand, Amanda M; Yoon, Do Young; Kim, Dong-Shik

    2014-11-15

    Peptide nanotubes (PNTs) encapsulating horseradish peroxidase and surface coated with acetylcholinesterase (AChE) were attached to gold screen printed electrodes to construct a novel gas phase organophosphate (OP) biosensor. When the sensor with the AChE enzyme is put in contact with acetylthiocholine (ATCh), the ATCh is hydrolyzed to produce thiocholine, which is then oxidized by horseradish peroxidase (HRP). Direct electron transfer between HRP and electrode is achieved through PNTs. The signal produced by the electron transfer is measured with cyclic voltammetry (CV). The presence of an OP compound inhibits this signal by binding with the AChE enzyme. In this study, gas phase malathion was used as a model OP due to the fact that it displays the identical binding mechanism with acetylcholinesterase (AChE) as its more potent counterparts such as sarin and VX, but has low toxicity, making it more practical and safer to handle. The CV signal was proportionally inhibited by malathion vapor concentrations as low as 12 ppbv. Depending on the method used in their preparation, the electrodes maintained their activity for up to 45 days. This research demonstrates the potential of applying nano-modified biosensors for the detection of low levels of OP vapor, an important development in countering weaponized organophosphate nerve agents and detecting commercially-used OP pesticides.

  20. Imidazole aldoximes effective in assisting butyrylcholinesterase catalysis of organophosphate detoxification.

    PubMed

    Sit, Rakesh K; Fokin, Valery V; Amitai, Gabriel; Sharpless, K Barry; Taylor, Palmer; Radić, Zoran

    2014-02-27

    Intoxication by organophosphate (OP) nerve agents and pesticides should be addressed by efficient, quickly deployable countermeasures such as antidotes reactivating acetylcholinesterase or scavenging the parent OP. We present here synthesis and initial in vitro characterization of 14 imidazole aldoximes and their structural refinement into three efficient reactivators of human butyrylcholinesterase (hBChE) inhibited covalently by nerve agent OPs, sarin, cyclosarin, VX, and the OP pesticide metabolite, paraoxon. Rapid reactivation of OP-hBChE conjugates by uncharged and nonprotonated tertiary imidazole aldoximes allows the design of a new OP countermeasure by conversion of hBChE from a stoichiometric to catalytic OP bioscavenger with the prospect of oral bioavailability and central nervous system penetration. The enhanced in vitro reactivation efficacy determined for tertiary imidazole aldoximes compared to that of their quaternary N-methyl imidazolium analogues is attributed to ion pairing of the cationic imidazolium with Asp 70, altering a reactive alignment of the aldoxime with the phosphorus in the OP-hBChE conjugate.

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

    SciTech Connect

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

    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. 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. -- 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.

  2. Organophosphate-Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

    DTIC Science & Technology

    2014-10-01

    subthreshold doses of OPs. Key Words: Pesticide, Organophosphate, Manganese Enhanced Magnetic Resonance Imaging, Gulf War Illness, Alzheimer ‟s...with OPs lies in the fact that reversible AChEs used to treat Alzheimer ‟s disease (e.g., donepezil) have pro-cognitive effects in humans and...favorable effects on the cognitive symptoms in Alzheimer disease (Becker et al., 1998). Prospective efforts to further elucidate the long term consequences

  3. 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.

  4. 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

  5. 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 ...

  6. 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...

  7. 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

  8. Developmental Exposure to Organophosphate Flame Retardants Elicits Overt Toxicity and Alters Behavior in Early Life Stage Zebrafish (Danio rerio)

    PubMed Central

    Dishaw, Laura V.; Hunter, Deborah L.; Padnos, Beth; Padilla, Stephanie; Stapleton, Heather M.

    2014-01-01

    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 the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish. PMID:25239634

  9. Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio).

    PubMed

    Dishaw, Laura V; Hunter, Deborah L; Padnos, Beth; Padilla, Stephanie; Stapleton, Heather M

    2014-12-01

    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 the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish.

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

    SciTech Connect

    Dekundy, Andrzej . E-mail: andrzej.dekundy@merz.de; Kaminski, Rafal M.; Zielinska, Elzbieta; Turski, Waldemar A.

    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 of 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.

  11. Imidazole Aldoximes Effective in Assisting Butyrylcholinesterase Catalysis of Organophosphate Detoxification

    PubMed Central

    2015-01-01

    Intoxication by organophosphate (OP) nerve agents and pesticides should be addressed by efficient, quickly deployable countermeasures such as antidotes reactivating acetylcholinesterase or scavenging the parent OP. We present here synthesis and initial in vitro characterization of 14 imidazole aldoximes and their structural refinement into three efficient reactivators of human butyrylcholinesterase (hBChE) inhibited covalently by nerve agent OPs, sarin, cyclosarin, VX, and the OP pesticide metabolite, paraoxon. Rapid reactivation of OP–hBChE conjugates by uncharged and nonprotonated tertiary imidazole aldoximes allows the design of a new OP countermeasure by conversion of hBChE from a stoichiometric to catalytic OP bioscavenger with the prospect of oral bioavailability and central nervous system penetration. The enhanced in vitro reactivation efficacy determined for tertiary imidazole aldoximes compared to that of their quaternary N-methyl imidazolium analogues is attributed to ion pairing of the cationic imidazolium with Asp 70, altering a reactive alignment of the aldoxime with the phosphorus in the OP–hBChE conjugate. PMID:24571195

  12. Body mass index as a prognostic factor in organophosphate-poisoned patients.

    PubMed

    Lee, Duk Hee; Jung, Koo Young; Choi, Yoon Hee; Cheon, Young Jin

    2014-07-01

    Organophosphate poisoning is a serious clinical entity and considerable morbidity and mortality. Several factors have been identified to predict outcomes of organophosphate poisoning. Organophosphates are lipophilic and therefore predicted to have a large volume of distribution and to rapidly distribute into tissue and fat. Thus, toxic effects of organophosphate would be expected to last longer in obese patients. We investigated the relationship between obesity and clinical course in 112 acute organophosphate-poisoned patients from an initial medical record review of 234 patients. One hundred twenty-two patients were excluded: 6 were children, 14 had an uncertain history of exposure and of uncertain agent, 10 were transferred to another hospital, 67 were discharged from the emergency department because their toxicity was mild, 21 had carbamate poisoning, and 4 did not have height or weight checked. Clinical features, body mass index, Glasgow Coma Scale, laboratory findings, serum cholinesterase activity, electrocardiogram finding, management, and outcomes were examined. The lipid solubility of the implicated organophosphate was characterized by its octanol/water coefficient. Forty of 112 patients were obese. Obese patients who were poisoned by high lipophilicity organophosphate compounds had a need for longer use of mechanical ventilation, intensive care unit care, and total length of admission. Body mass index can provide a guide to physicians in predicting clinical course and management in organophosphate-poisoned patients.

  13. Immobilization of organophosphate hydrolase on biocompatible gelatin pads and its use in removal of organophosphate compounds and nerve agents.

    PubMed

    Kanugula, Anantha KoteswaraRao; Repalle, Elisha Raju; Pandey, Jay Prakash; Sripad, Gunwar; Mitra, Chanchal Kumar; Dubey, Devender Kumar; Siddavattam, Dayananda

    2011-02-01

    Bacterial organophosphate hydrolases (OPH) have been shown to hydrolyze structurally diverse group of organophosphate (OP) compounds and nerve agents. Due to broad substrate range and unusual catalytic properties, the OPH has successfully been used to develop eco-friendly strategies for detection and decontamination of OP compounds. However, their usage has failed to gain necessary acceptance, due to short half-life of the enzyme and loss of activity during process development. In the present study, we report a simple procedure for immobilization of OPH on biocompatible gelatin pads. The covalent coupling of OPH using glutaraldehyde spacer has been found to dramatically improve the enzyme stability. There is no apparent loss of OPH activity in OPH-gelatin pads stored at room temperature for more than six months. As revealed by a number of kinetic parameters, the catalytic properties of immobilized enzyme are found to be comparable to the free enzyme. Further, the OPH-gelatin pads effectively eliminate OP insecticide methyl parathion and nerve agent sarin.

  14. 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.

  15. Detoxification of organophosphate residues using phosphotriesterase and their evaluation using flow based biosensor.

    PubMed

    Mishra, Rupesh K; Istamboulie, George; Bhand, Sunil; Marty, Jean-Louis

    2012-10-01

    Among known pesticide groups, organophosphates (OPs) have grasped attention due to their hazardous nature and their applications as pesticides and chemical weapons. This work presents the development of cost-effective column based biosensor for detoxification of OPs in water and milk. Enzyme phosphotriesterase (PTE) was immobilized on an activated Sepharose 4B via covalent coupling using an Omnifit glass column. Three different OPs, ethyl paraoxon (EPOx), malaoxon (MAO) and chlorpyriphos-oxon (CPO) were spiked in water and milk to test the detoxification of OPs. Mixtures of these pesticides were also tested to check the cumulative detoxification in the real samples. The efficiency of detoxification was evaluated using a highly sensitive acetylcholinesterase (AChE) B394 biosensor based flow system. The column conditions were optimized for the detoxification studied. The method was shown to be promising when we tested real milk samples spiked with OPs. Detoxification obtained in milk was up to 86% whereas in water, 100% detoxification was obtained.

  16. Organophosphate esters in dust samples collected from Danish homes and daycare centers.

    PubMed

    Langer, Sarka; Fredricsson, Malin; Weschler, Charles J; Bekö, Gabriel; Strandberg, Bo; Remberger, Mikael; Toftum, Jørn; Clausen, Geo

    2016-07-01

    Organophosphates are used in a wide range of materials and consumer products and are ubiquitous in indoor environments. Certain organophosphates have been associated with various adverse health effects. The present paper reports mass fractions of organophosphates in dust samples collected from 500 bedrooms and 151 daycare centers of children living in Odense, Denmark. The identified compounds include: tris(isobutyl) phosphate (TIBP), tri-n-butyl phosphate (TNBP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP), tris(2-butoxyethyl) phosphate (TBOEP), triphenylphosphate (TPHP), 2-ethylhexyl-diphenyl phosphate (EHDPP), tris(2-ethylhexyl) phosphate (TEHP) and tris(methylphenyl) phosphate (TMPP). Both the number of organophosphates with median values above the limit of detection and the median values were higher for samples from daycare centers than for samples from homes. Organophosphates with median mass fractions above the limit of detection were: TCEP from homes (6.9 μg g(-1)), and TCEP (16 μg g(-1)), TCIPP (5.6 μg g(-1)), TDCIPP (7.1 μg g(-1)), TBOEP (26 μg g(-1)), TPHP (2.0 μg g(-1)) and EHDPP (2.1 μg g(-1)) from daycare centers. When present, TBOEP was typically the most abundant of the identified OPs. The sum of the organophosphate dust mass fractions measured in this study was roughly in the mid-range of summed mass fractions reported for dust samples collected in other countries. On a global scale, the geographical distribution of organophosphates in indoor dust is quite variable, with higher concentrations in industrialized countries. This trend differs from that for phthalate esters, whose geographic distribution is more homogeneous. Exposure to organophosphates via dust ingestion is relatively low, although there is considerable uncertainly in this assessment.

  17. Organophosphate Flame Retardants and Plasticizers in Aqueous Solution: pH-Dependent Hydrolysis, Kinetics, and Pathways.

    PubMed

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

    2016-08-02

    Despite the growing ubiquity of organophosphate (OP) triesters as environmental contaminants, parameters affecting their aquatic chemical stabilities are currently unknown. The present study examined the pH-dependent (7, 9, 11, or 13) hydrolysis of 16 OP triesters in mixtures of 80 ng/mL for each OP triester over a period of 35 days at 20 °C. For the pH = 7, 9, and 11 solutions, 10 of the 16 OP triesters were stable and with no significant (p > 0.05) degradation. For the remaining 6 OP triesters, significant degradation occurred progressing from the pH = 7 to 11 solutions. At pH = 13, except for tributyl phosphate and tris(2-ethylhexyl) phosphate, 14 OP triesters were degraded with half-lives ranging from 0.0053 days (triphenyl phosphate) to 47 days (tripropyl phosphate). With increasingly basic pH the order of OP triester stability was group A (with alkyl moieties) > group B (chlorinated alkyl) > group C (aryl). Numerous OP diesters were identified depending on the pH level of the solution, whereas OP monoesters were not detectable. This is consistent with no significant (p > 0.05) depletion observed for 5 OP diesters in the same 4 solutions and over same 35 day period, suggesting OP diesters are end products of base-catalyzed hydrolysis of OP triesters. Our results demonstrated that pH-dependent hydrolysis of OP triesters does occur, and such instability would likely affect the fate of OP triesters in aqueous environments where the pH can be variable and basic.

  18. Fe2O3 nanoparticles for airborne organophosphate detection

    NASA Astrophysics Data System (ADS)

    Phillips, Joshua; Soliz, Jennifer; Hauser, Adam

    Dire need for early detection of organophosphates (OP) exists in both civilian (pesticide/herbicide buildup) and military (G/V nerve agents) spheres. Nanoparticle materials are excellent candidates for the detection and/or decontamination of hazardous materials, owing to their large surface to volume ratios and tailored surface functionality. Within this category, metal oxides include structures that are stable with the range of normal environmental conditions (temperature, humidity), but have strong, specific reaction mechanisms (hydrolysis, oxidation, catalysis, stoichiometric reaction) with toxic compounds. In this talk, we will present on the suitability of Fe2O3 nanoparticles as airborne organophosphate detectors. 23 nm particles were exposed to a series of organophosphate compounds (dimethyl methylphosphonate, dimethyl chlorophosphonate, diisopropyl methylphosphonate), and studied by x-ray magnetic circular dichroism and x-ray absorption spectroscopy to confirm the stoichiometric Fe2O3 to FeO mechanism and determine magnetic sensor feasibility. AC Impedance Spectroscopy shows both high sensitivity and selectivity via frequency dependence in both impedance and resistivity, suggesting some feasibility for impedimetric devices. We acknowledge funding under Army Research Office STIR Award #W911F-15-1-0104. J.R.S. acknowledges funding from the Defense Threat Reduction Agency under Projects BA13PHM210 and BA07PRO104. J.R.S. also acknowledges funding under a NRC fellowship.

  19. 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...

  20. Genetic factors potentially reducing fitness cost of organophosphate-insensitive acetylcholinesterase(s) in Rhipicephalus (Boophilus) microplus (Acari: Ixodidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acaricidal activity of organophosphate (OP) and carbamate acaricides is believed to result from inhibition of acetylcholinesterase (AChE). Previous studies in Rhipicephalus (Boophilus) microplus demonstrated the presence of three presumptive AChE genes (BmAChEs). Biochemical characterization of re...

  1. 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.

  2. Identification of an opd (Organophosphate Degradation) Gene in an Agrobacterium Isolate

    PubMed Central

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

    2002-01-01

    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 kcat than OPH. It was also capable of hydrolyzing the dimethyl OPs phosmet and fenthion, which were not hydrolyzed at detectable levels by OPH. PMID:12089017

  3. Caramiphen edisylate: an optimal antidote against organophosphate poisoning.

    PubMed

    Raveh, Lily; Eisenkraft, Arik; Weissman, Ben Avi

    2014-11-05

    Potent cholinesterase inhibitors such as sarin, induce an array of harmful effects including hypersecretion, convulsions and ultimately death. Surviving subjects demonstrate damage in specific brain regions that lead to cognitive and neurological dysfunctions. An early accumulation of acetylcholine in the synaptic clefts was suggested as the trigger of a sequence of neurochemical events such as an excessive outpour of glutamate and activation of its receptors. Indeed, alterations in NMDA and AMPA central receptors' densities were detected in brains of poisoned animals. Attempts to improve the current cholinergic-based treatment by adding potent anticonvulsants or antiglutamatergic drugs produced unsatisfactory results. In light of recent events in Syria and the probability of various scenarios of military or terrorist attacks involving organophosphate (OP) nerve agent, research should focus on finding markedly improved countermeasures. Caramiphen, an antimuscarinic drug with antiglutamatergic and GABAergic facilitating properties, was evaluated in a wide range of animals and experimental protocols against OP poisoning. Its remarkable efficacy against OP exposure was established both in prophylactic and post-exposure therapies in both small and large animals. The present review will highlight the outstanding neuroprotective effect of caramiphen as the optimal candidate for the treatment of OP-exposed subjects.

  4. Can anisodamine be a potential substitute for high-dose atropine in cases of organophosphate poisoning?

    PubMed

    Wang, W; Chen, Q-F; Ruan, H-L; Chen, K; Chen, B; Wen, J-M

    2014-11-01

    A case of organophosphate (OP) poisoning was admitted to the emergency room. The patient accepted treatment with pralidoxime (PAM), atropine, and supporting therapy. It was observed that even after 22 h after treatment, 960 mg of atropine was not enough for the patient to be atropinized. However, a 160-mg follow-up treatment of anisodamine was quite enough for atropinization after 4 h. As a case report, more studies are required before any definite conclusion can be reached regarding the use of anisodamine as a potential substitute for high-dose atropine in cases of OP poisoning.

  5. Organophosphate and Pyrethroid Hydrolase Activities of Mutant Esterases from the Cotton Bollworm Helicoverpa armigera

    PubMed Central

    Li, Yongqiang; Farnsworth, Claire A.; Coppin, Chris W.; Teese, Mark G.; Liu, Jian-Wei; Scott, Colin; Zhang, Xing; Russell, Robyn J.; Oakeshott, John G.

    2013-01-01

    Two mutations have been found in five closely related insect esterases (from four higher Diptera and a hymenopteran) which each confer organophosphate (OP) hydrolase activity on the enzyme and OP resistance on the insect. One mutation converts a Glycine to an Aspartate, and the other converts a Tryptophan to a Leucine in the enzymes’ active site. One of the dipteran enzymes with the Leucine mutation also shows enhanced activity against pyrethroids. Introduction of the two mutations in vitro into eight esterases from six other widely separated insect groups has also been reported to increase substantially the OP hydrolase activity of most of them. These data suggest that the two mutations could contribute to OP, and possibly pyrethroid, resistance in a variety of insects. We therefore introduced them in vitro into eight Helicoverpa armigera esterases from a clade that has already been implicated in OP and pyrethroid resistance. We found that they do not generally enhance either OP or pyrethroid hydrolysis in these esterases but the Aspartate mutation did increase OP hydrolysis in one enzyme by about 14 fold and the Leucine mutation caused a 4–6 fold increase in activity (more in one case) of another three against some of the most insecticidal isomers of fenvalerate and cypermethrin. The Aspartate enzyme and one of the Leucine enzymes occur in regions of the H. armigera esterase isozyme profile that have been previously implicated in OP and pyrethroid resistance, respectively. PMID:24204917

  6. Refolded Recombinant Human Paraoxonase 1 Variant Exhibits Prophylactic Activity Against Organophosphate Poisoning.

    PubMed

    Bajaj, Priyanka; Tripathy, Rajan K; Aggarwal, Geetika; Datusalia, Ashok K; Sharma, Shyam S; Pande, Abhay H

    2016-09-01

    Organophosphate (OP) compounds are neurotoxic chemicals, and current treatments available for OP-poisoning are considered as unsatisfactory and inadequate. There is an urgent need for the development of more effective treatment(s) for OP-poisoning. Human paraoxonase 1 (h-PON1) is known to hydrolyze a variety of OP-compounds and is a leading candidate for the development of prophylactic and therapeutic agent against OP-poisoning in humans. Non-availability of effective system(s) for the production of recombinant h-PON1 (rh-PON1) makes it hard to produce improved variant(s) of this enzyme and analyze their in vivo efficacy in animal models. Production of recombinant h-PON1 (rh-PON1) using an Escherichia coli expression system is a key to develop variant(s) of h-PON1. Recently, we have developed a procedure to produce active rh-PON1 enzymes by using E. coli expression system. In this study, we have characterized the OP-hydrolyzing properties of refolded rh-PON1(wt) and rh-PON1(H115W;R192K) variant. Our results show that refolded rh-PON1(H115W;R192K) variant exhibit enhanced OP-hydrolyzing activity in in vitro and ex vivo assays and exhibited prophylactic activity in mouse model of OP-poisoning, suggesting that refolded rh-PON1 can be developed as a therapeutic candidate.

  7. 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.

  8. α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology.

    PubMed

    Piermartiri, Tetsade; Pan, Hongna; Figueiredo, Taiza H; Marini, Ann M

    2015-11-12

    α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders.

  9. Intravenous lipid emulsions combine extracorporeal blood purification: a novel therapeutic strategy for severe organophosphate poisoning.

    PubMed

    Zhou, Yaguang; Zhan, Chengye; Li, Yongsheng; Zhong, Qiang; Pan, Hao; Yang, Guangtian

    2010-02-01

    Organophosphorus (OP) pesticide self-poisoning is a major clinical problem in rural Asia and it results in the death of 200,000 people every year. At present, it is lack of effective methods to treat severe organophosphate poisoning. The high mortality rate lies on the amount of toxic absorption. Intravenous lipid emulsions can be used as an antidote in fat-soluble drug poisoning. The detoxification mechanism of intravenous lipid emulsions is "lipid sink", which lipid emulsions can dissolve the fat-soluble drugs and separate poison away from the sites of toxicity. Most of organophosphorus pesticides are highly fat-soluble. So, intravenous lipid emulsions have the potentially clinical applications in treatment of OP poisoning. Extracorporeal blood purification especially charcoal hemoperfusion is an efficient way to eliminate the poison contents from the blood. We hypothesize that the combination of intravenous lipid emulsions and charcoal hemoperfusion can be used to cure severe organophosphate poisoning. This novel protocol of therapy comprises two steps: one is obtained intravenous access to infuse lipid emulsions as soon as possible; another is that charcoal hemoperfusion will be used to clear the OP substances before the distribution of OP compounds in tissue is not complete. The advantages of this strategy lie in three points. Firstly, it will alleviate the toxic effect of OP pesticide in the patients by isolation and removal the toxic contents. Secondly, the dosage of antidotes can be reduced and its side-effects will be eased. Thirdly, a large bolus of fatty acids provide energy substrate for the patients who are nil by mouth. We consider that it would become a feasible, safe and efficient detoxification intervention in the alleviation of severe organophosphate poisoning, which would also improve the outcome of the patients.

  10. Organophosphates, serine esterase inhibition, and modeling of organophosphate toxicity.

    PubMed

    Chambers, Janice; Oppenheimer, Seth F

    2004-02-01

    The highlighted article in this issue (Ashani and Pistinner, "Estimation of the Upper Limit of Human Butyrylcholinesterase Dose Required for Protection against Organophosphates toxicity: A Mathematically Based Toxicokinetic Model") is an innovative approach to modeling the amount of protective enzyme, human butyrylcholinesterase, that could be administered to humans to protect them from the lethal effects of organophosphate nerve agents. The threat of nerve agent exposures at lethal level regrettably remains a threat to military as well civilian populations, and the authors of this article have used their previous experimental data along with new in vitro data to devise and calibrate a mathematical model that could have practical utility in the prophylaxis of military personnel against chemical warfare agents.

  11. 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

  12. Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers.

    PubMed

    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

    2015-06-23

    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 AChE 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.

  13. 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

  14. Organophosphate and carbamate intoxication in La Paz, Bolivia.

    PubMed

    Exner, Christopher J; Ayala, Guillermo Urquizo

    2009-05-01

    Intoxication with organophosphate (OP) and carbamate (CM) compounds is a common reason for presentation to the Emergency Department (ED) in La Paz, Bolivia. The objective of this study was to describe the demographics, presenting symptoms, and hospital course of patients presenting with OP or CM intoxication to the ED of the Hospital de Clinicas, La Paz, Bolivia, with the aim of determining which factors might predict a complicated hospital course. This was a retrospective chart review, using predefined criteria, of 300 patients who presented from January 1, 2003 to December 31, 2003. The intoxications were all oral, mostly intentional (97%), and in young patients (mean age 23.9 years, range 13-62 years). Females outnumbered males almost 2:1. The most common symptoms on presentation were abdominal pain (83%), nausea/vomiting (79%), miosis (72%), bronchorrhea (44%), diarrhea (41%), and fasciculations (31%). The most frequent complications were aspiration (18%), cardiopulmonary arrest (9%), and seizure (7%); mortality was 6%. Treatments included gastric lavage in 96% of patients, and atropine (median 5 mg per patient, range 0-48 mg). Miosis, bronchorrhea, diarrhea, and fasciculations at presentation were associated with a higher rate of complications. Although almost all intoxications were suicide attempts, less than half of patients received a psychiatric consultation. OP intoxication is a common cause of self-inflicted morbidity and mortality among young people in La Paz, Bolivia. Presence of miosis, bronchorrhea, diarrhea, and fasciculations at presentation suggest a higher likelihood of complications.

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

    SciTech Connect

    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 can 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.

  16. Comparison of wastewater treatment processes on the removal efficiency of organophosphate esters.

    PubMed

    Pang, Long; Yang, Peijie; Zhao, Jihong; Zhang, Hongzhong

    2016-10-01

    Organophosphate esters (OPs), widely used as flame retardants and plasticizers, are regarded as a class of emerging pollutants. The effluent of municipal wastewater treatment plants is generally considered to be the main contributor of OP pollution to the surface water. In this study, anoxic-oxic (AO) and University of Capetown (UCT) processes were selected to investigate the removal efficiency of OPs. The results indicated that the UCT process showed better removal efficiency than that of the AO process. For the chlorinated OPs, approximately 12.3% of tri(2-chloroethyl)phosphate and 11.8% of tri(chloropropyl)phosphate can be removed in the UCT process, which was 12% and 7.8% higher than that of the AO process. In contrast, non-chlorinated OPs, including tris(2-butoxyethyal)phosphate, triphenyl phosphate, and tributyl phosphate, were able to be removed in both processes, with the removal rate of 85.1%, 74.9%, and 29.1% in the AO process, and 88.4%, 63.6%, and 25.2% in the UCT process. Furthermore, linear correlation between the removal rate and logKow of OPs (r(2) = 0.539) was observed in the AO process, indicating that OPs with high Kow value (e.g. tri(dichloropropyl)phosphate and triphenyl phosphate) are prone to be removed by adsorption on the residual activated sludge.

  17. B-esterase determination and organophosphate insecticide inhibitory effects in JEG-3 trophoblasts.

    PubMed

    Espinoza, Marlon; Rivero Osimani, Valeria; Sánchez, Victoria; Rosenbaum, Enrique; Guiñazú, Natalia

    2016-04-01

    The placenta and trophoblasts express several B-esterases. This family includes acethylcholinesterase (AChE), carboxylesterase (CES) and butyrylcholinesterase (BChE), which are important targets of organophosphate insecticide (OP) toxicity. To better understand OP effects on trophoblasts, B-esterase basal activity and kinetic behavior were studied in JEG-3 choriocarcinoma cell cultures. Effects of the OP azinphos-methyl (Am) and chlorpyrifos (Cp) on cellular enzyme activity were also evaluated. JEG-3 cells showed measurable activity levels of AChE and CES, while BChE was undetected. Recorded Km for AChE and CES were 0.33 and 0.26 mM respectively. Native gel electrophoresis and RT-PCR analysis demonstrated CES1 and CES2 isoform expression. Cells exposed for 4 and 24 h to the OP Am or Cp, showed a differential CES and AChE inhibition profiles. Am inhibited CES and AChE at 4 h treatment while Cp showed the highest inhibition profile at 24 h. Interestingly, both insecticides differentially affected CES1 and CES2 activities. Results demonstrated that JEG-3 trophoblasts express AChE, CES1 and CES2. B-esterase enzymes were inhibited by in vitro OP exposure, indicating that JEG-3 cells metabolization capabilities include phase I enzymes, able to bioactivate OP. In addition, since CES enzymes are important for medicinal drug activation/deactivation, OP exposure may interfere with trophoblast CES metabolization, probably being relevant in a co-exposure scenario during pregnancy.

  18. 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...

  19. 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

  20. Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study

    PubMed Central

    Lerro, Catherine C.; Koutros, Stella; Andreotti, Gabriella; Friesen, Melissa C.; Alavanja, Michael C.; Blair, Aaron; Hoppin, Jane A.; Sandler, Dale P.; Lubin, Jay H.; Ma, Xiaomei; Zhang, Yawei; Beane Freeman, Laura E.

    2016-01-01

    Objectives Organophosphates (OP) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiologic studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. Methods At enrollment (1993–1997) spouses provided information about ever use of specific pesticides, including ten OPs, demographic information, reproductive health history, and other potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) for all cancers diagnosed through 2010 for North Carolina and 2011 for Iowa. Results Among 30,003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR = 1.20, 95% CI: 1.01, 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR = 2.04, 95% CI: 1.14, 3.63) and decreased risk of non-Hodgkin lymphoma (RR = 0.64, 95% CI: 0.41, 0.99). Diazinon use was associated with ovarian cancer (RR = 1.87, 95% CI: 1.02, 3.43). Conclusions We observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid, and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus a need for further evaluation. PMID:26150671

  1. 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.

  2. Is there a relationship between the WHO hazard classification of organophosphate pesticide and outcomes in suicidal human poisoning with commercial organophosphate formulations?

    PubMed

    Peter, John Victor; Jerobin, Jayakumar; Nair, Anupama; Bennett, Anjana

    2010-06-01

    The WHO classification of pesticides by hazard is based primarily on the acute oral and dermal toxicity to rats. In several Asian countries there is no legislation against the sale of Class I insecticides. We evaluated if there was an association between the WHO hazard Class I, II or III organophosphate compound and outcomes in human poisoning. Two-hundred and fifty-one patients with mean (SD) age of 30.4 (11.8) years, admitted with symptomatic poisoning and treated with atropine and supportive care, were followed up until death or hospital discharge. The admission pseudocholinesterase level of 818.8 (1368) IU/L indicated significant suppression of cholinesterase activity. Class I compounds were ingested by 126, Class II by 113 and Class III by 12 patients. The hospital mortality rate was 16.7%, 5.3% and 0% with Class I, II and III organophosphate compounds, respectively (P=0.01). Ventilatory requirements were higher with Class I compared with Class II poisoning (77.0% vs. 54.9%, P<0.001). Patients with Class I poisoning needed mechanical ventilation for a longer period (10.55 (7.4) vs. 7.0 (5.2) days, P=0.002). The linear relationship between the WHO hazard class and mortality in acute organophosphate poisoning mandates the restriction of the sale of organophosphate compounds associated with higher lethality amongst humans.

  3. Aquatic hazard assessment of the organophosphate insecticide fonofos

    USGS Publications Warehouse

    Fairchild, James F.; Little, Edward E.; Huckins, James N.

    1992-01-01

    This study determined the acute and chronic toxicity of the organophosphate insecticide fonofos to standard freshwater aquatic organisms under laboratory conditions. Fonofos was acutely toxic to bluegill (Lepomis macrochirus), Daphnia (D. magna), and midge (Chironomous riparius) at 5.3, 2.7, and 39 μg/L, respectively. Three fonofos formulations (technical, 94.8% A.I.; 20G, field granular 20% A.I.; and 4E, field liquid 4#/gal A.I.) exhibited similar acute toxicities to bluegill. Exposure to fonofos delayed reproduction and decreased the intrinsic rate of increase of Daphnia during 21-d chronic exposure at the lowest tested concentration (0.08 μg/L). The no observable effect concentration (NOEC) for Daphnia survival was 0.42 μg/L; 0% survival occurred at the lowest observable effect concentration (LOEC) of 1.45 μg/L. The NOEC for midge emergence was 3.42 μg/L; only 34% emergence occurred at the LOEC of 8.24 μg/L. Chronic 30-d exposure of juvenile bluegills decreased growth and survival at 5.65 μg/L (LOEC), but no effects occurred at 2.33 μg/L (NOEC). The relative hazard of fonofos to aquatic life is similar to other carbamate and organophosphate corn insecticides.

  4. Organophosphates and monocyte esterase deficiency.

    PubMed Central

    McClean, E; Mackey, H; Markey, G M; Morris, T C

    1995-01-01

    AIMS--To examine the possibility that monocyte esterase deficiency (MED) could be caused by exposure to organophosphates. METHODS--Pseudocholinesterase, paraoxonase and arylesterase activities were measured in the serum and acetylcholinesterase activity was measured in the red cells of a group of monocyte esterase deficient subjects and compared with the enzyme activities of a control group of monocyte esterase positive subjects. RESULTS--No significant difference was found between the enzyme activities of the monocyte esterase deficient group and the control group for any of the esterases investigated. CONCLUSION--Current or recent exposure to organophosphorus is not the cause of MED. PMID:7560207

  5. Oxidative stress indices in Nigerian pesticide applicators and farmers occupationally exposed to organophosphate pesticides

    PubMed Central

    Surajudeen, Yaqub A; Sheu, Rahamon K; Ayokulehin, Kosoko M; Olatunbosun, Arinola G

    2014-01-01

    Background: Reports have clearly indicated the role of oxidative stress in the pathogenesis of organophosphate pesticides (Op) toxicity. However, there is dearth of information on which group of the farm workers is more at risk of Op-induced oxidative stress. Aim: This study determined serum levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), myeloperoxidase (MPO), nitric oxide (NO), and serum activity of acetylcholinesterase (AChE) in farm workers exposed to Op. Subjects and Methods: A total of 60 (30 pesticide applicators and 30 farmers) and 30 apparently healthy non-farmers who were nonexposed to Op (controls) were recruited into this study. Serum activity of AChE was determined using high performance liquid chromatography (HPLC), while serum levels of MDA, GSH, and NO and serum activities of CAT, MPO, GPx, and superoxide dismutase (SOD) were determined colorimetrically. Results: Serum activities of AChE and CAT were significantly lower, whereas MPO activity was significantly higher in pesticide applicators compared with controls. Similarly, farmers had significantly reduced serum AChE activity and significantly raised MPO activity compared with controls. However, serum activities of AChE, CAT, and MPO were significantly lower, whereas mean level of MDA was significantly higher in pesticide applicators compared with farmers. Conclusion: This study shows that Op applicators are more exposed to oxidative stress than farmers, thus Op applicators require increased antioxidant supplements than farmers. PMID:25298941

  6. Occupational exposure limits for 30 organophosphate pesticides based on inhibition of red blood cell acetylcholinesterase.

    PubMed

    Storm, J E; Rozman, K K; Doull, J

    2000-09-07

    Toxicity and other relevant data for 30 organophosphate pesticides were evaluated to suggest inhalation occupational exposure limits (OELs), and to support development of a risk assessment strategy for organophosphates in general. Specifically, the value of relative potency analysis and the predictability of inhalation OELs by acute toxicity measures and by repeated oral exposure NOELs was assessed. Suggested OELs are based on the prevention of red blood cell (RBC) acetylcholinesterase (AChE) inhibition and are derived using a weight-of-evidence risk assessment approach. Suggested OEL values range from 0.002 to 2 mg/m(3), and in most cases, are less than current permissible exposure levels (PELs) or threshold limit values(R) (TLVs(R)). The available data indicate that experimental data for most organophosphates evaluated are limited; most organophosphates are equally potent RBC AChE inhibitors in different mammalian species; NOELs from repeated exposure studies of variable duration are usually equivalent; and, no particular grouping based on organophosphate structure is consistently more potent than another. Further, relative potency analyses have limited usefulness in the risk assessment of organophosphates. The data also indicated that equivalent relative potency relationships do not exist across either exposure duration (acute vs. repeated) or exposure route (oral vs. inhalation). Consideration of all variable duration and exposure route studies are therefore usually desirable in the development of an OEL, especially when data are limited. Also, neither acute measures of toxicity nor repeated oral exposure NOELs are predictive of weight-of-evidence based inhalation OELs. These deviations from what is expected based on the common mechanism of action for organophosphates across exposure duration and route - AChE inhibition - is likely due to the lack of synchrony between the timing of target tissue effective dose and the experimental observation of equivalent

  7. Longitudinal trends in organophosphate incidents reported to the National Pesticide Information Center, 1995–2007

    PubMed Central

    2009-01-01

    Background Regulatory decisions to phase-out the availability and use of common organophosphate pesticides among the general public were announced in 2000 and continued through 2004. Based on revised risk assessments, chlorpyrifos and diazinon were determined to pose unacceptable risks. To determine the impact of these decisions, organophosphate (OP) exposure incidents reported to the National Pesticide Information Center (NPIC) were analyzed for longitudinal trends. Methods Non-occupational human exposure incidents reported to NPIC were grouped into pre- (1995–2000) and post-announcement periods (2001–2007). The number of total OP exposure incidents, as well as reports for chlorpyrifos, diazinon and malathion, were analyzed for significant differences between these two periods. The number of informational inquiries from the general public was analyzed over time as well. Results The number of average annual OP-related exposure incidents reported to NPIC decreased significantly between the pre- and post-announcement periods (p < 0.001). A significant decrease in the number of chlorpyrifos and diazinon reports was observed over time (p < 0.001). No significant difference in the number of incident reports for malathion was observed (p = 0.4), which was not phased-out of residential use. Similar to exposure incidents, the number of informational inquiries received by NPIC declined over time following the phase-out announcement. Conclusion Consistent with other findings, the number of chlorpyrifos and diazinon exposure incidents reported to NPIC significantly decreased following public announcement and targeted regulatory action. PMID:19379510

  8. Coacervate Core Micelles for the Dispersion and Stabilization of Organophosphate Hydrolase in Organic Solvents

    NASA Astrophysics Data System (ADS)

    Mills, Carolyn; Obermeyer, Allie; Dong, Xuehui; Olsen, Bradley D.

    Bulk organophosphate (OP) nerve agents are difficult to decontaminate on site and dangerous to transport. The organophosphate hydrolase (OPH) enzyme is an efficient catalyst for hydrolyzing, and thus decontaminating, these compounds, but suffers from poor stability in the hydrophobic bulk OP environment. Here, we exploit the complex coacervation phase separation phenomenon to form complex coacervate core micelles (C3Ms) that can protect this OPH enzyme under these conditions. Stable C3Ms form when mixing a charged-neutral block copolymer methyl-quaternized poly(4-vinylpyridine)-block-poly(oligo(ethylene glycol) methacrylate) (Qp4vp- b-POEGMA), a homopolymer poly(acrylic acid) (PAA), and OPH under a certain conditions. The C3Ms are then transferred into two organic solvents, ethanol and dimethyl methylphosphonate (DMMP), which is a good simulant for the physical properties of the OP compounds. The C3Ms retain their nanostructures in the organic solvents. The activity test of OPH indicates that the C3Ms successfully protect OPH activity in organic solvents.

  9. Detection of trace levels of organophosphate pesticides using an electronic tongue based on graphene hybrid nanocomposites.

    PubMed

    Facure, Murilo H M; Mercante, Luiza A; Mattoso, Luiz H C; Correa, Daniel S

    2017-05-15

    Organophosphate (OP) compounds impose significant strains on public health, environmental/food safety and homeland security, once they have been widely used as pesticides and insecticides and also display potential to be employed as chemical warfare agents by terrorists. In this context, the development of sensitive and reliable chemical sensors that would allow in-situ measurements of such contaminants is highly pursued. Here we report on a free-enzyme impedimetric electronic tongue (e-tongue) used in the analysis of organophosphate pesticides comprising four sensing units based on graphene hybrid nanocomposites. The nanocomposites were prepared by reduction of graphene oxide in the presence of conducting polymers (PEDOT:PSS and polypyrrole) and gold nanoparticles (AuNPs), which were deposited by drop casting onto gold interdigitated electrodes. Impedance spectroscopy measurements were collected in triplicate for each sample analyzed, and the electrical resistance data were treated by Principal Component Analysis (PCA), revealing that the system was able to discriminate OPs at nanomolar concentrations. In addition, the electronic tongue system could detect OPs in real samples, where relations between the principal components and the variation of pesticides in a mixture were established, proving to be useful to analyze and monitor mixtures of OP pesticides. The materials employed provided sensing units with high specific surface area and high conductivity, yielding the development of a sensor with suitable stability, good reproducibility, and high sensitivity towards pesticide samples, being able to discriminate concentrations as low as 0.1nmolL(-1). Our results indicate that the e-tongue system can be used as a rapid, simple and low cost alternative in the analyses of OPs pesticide solutions below the concentration range permitted by legislation of some countries.

  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. 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.

  12. Optimization of Therapeutic Strategies for Organophosphate Poisoning

    DTIC Science & Technology

    2008-03-01

    reaction rate constants (Thiermann and others, 1999:234). In 2007, Bartling , Worek, Szinicz, and Thiermann investigated the reactions between...organophosphates and esterases ( Bartling and others 2007:166). In their article the researchers provided chemical kinetic rate constants for several...organophosphates, which proved useful for the work presented in this thesis ( Bartling and others, 2007:169). 31 III. Methodology Modeling Tool Model

  13. Immunomodulation by poly-YE reduces organophosphate-induced brain damage.

    PubMed

    Finkelstein, Arseny; Kunis, Gilad; Berkutzki, Tamara; Ronen, Ayal; Krivoy, Amir; Yoles, Eti; Last, David; Mardor, Yael; Van Shura, Kerry; McFarland, Emylee; Capacio, Benedict A; Eisner, Claire; Gonzales, Mary; Gregorowicz, Danise; Eisenkraft, Arik; McDonough, John H; Schwartz, Michal

    2012-01-01

    Accidental organophosphate poisoning resulting from environmental or occupational exposure, as well as the deliberate use of nerve agents on the battlefield or by terrorists, remain major threats for multi-casualty events, with no effective therapies yet available. Even transient exposure to organophosphorous compounds may lead to brain damage associated with microglial activation and to long-lasting neurological and psychological deficits. Regulation of the microglial response by adaptive immunity was previously shown to reduce the consequences of acute insult to the central nervous system (CNS). Here, we tested whether an immunization-based treatment that affects the properties of T regulatory cells (Tregs) can reduce brain damage following organophosphate intoxication, as a supplement to the standard antidotal protocol. Rats were intoxicated by acute exposure to the nerve agent soman, or the organophosphate pesticide, paraoxon, and after 24 h were treated with the immunomodulator, poly-YE. A single injection of poly-YE resulted in a significant increase in neuronal survival and tissue preservation. The beneficial effect of poly-YE treatment was associated with specific recruitment of CD4(+) T cells into the brain, reduced microglial activation, and an increase in the levels of brain derived neurotrophic factor (BDNF) in the piriform cortex. These results suggest therapeutic intervention with poly-YE as an immunomodulatory supplementary approach against consequences of organophosphate-induced brain damage.

  14. A rodent model of human organophosphate exposure producing status epilepticus and neuropathology.

    PubMed

    Pouliot, W; Bealer, S L; Roach, B; Dudek, F E

    2016-09-01

    Exposure to organophosphates (OPs) often results in seizures and/or status epilepticus (SE) that produce neural damage within the central nervous system (CNS). Early control of SE is imperative for minimizing seizure-related CNS neuropathology. Although standard therapies exist, more effective agents are needed to reduce OP-induced SE and neuronal loss, particularly therapies with efficacy when administered 10's of minutes after the onset of SE. To evaluate novel antiseizure compounds, animal models should simulate the CNS effects of OP exposure observed in humans. We characterized in rats the effects of the OP, diisopropyl flourophosphate (DFP) as a function of dose and route of administration of supporting agents (pyridostigmine, 2-PAM, atropine); outcome measures were mortality, electrographic seizure activity during SE, and subsequent CNS neuropathology. Doses of DFP between 3 and 7mg/kg consistently caused SE, and the latency to behavioral tremors and to subsequent initiation of SE were dose related. In distinction, all doses of DFP that resulted in electrographic SE (3-7mg/kg) produced seizures of similar intensity and duration, and similar CNS neuropathology (i.e., the effects were all-or-none). Although SE was similar across doses, mortality progressively increased with higher doses of DFP. Mortality was significantly lower when the route of administration of therapeutic agents was intramuscular compared to intraperitoneal. This rodent model of OP poisoning demonstrates pathological characteristics similar to those observed in humans, and thus begins to validate this model for investigating potential new therapeutic approaches.

  15. Construction of a genetically engineered microorganism that simultaneously degrades organochlorine and organophosphate pesticides.

    PubMed

    Yang, Jijian; Liu, Ruihua; Song, Wenli; Yang, Yao; Cui, Feng; Qiao, Chuanling

    2012-02-01

    Field contamination with pesticide mixtures of organophosphates (OPs) and organochlorines (OCs) is becoming global issues to be solved urgently. The strategy of utilizing engineered microorganisms that have an ability to simultaneously degrade OPs and OCs has increasingly received great interest. In this work, an OP degradation gene (mpd) and an OC degradation gene (linA) were simultaneously introduced into Escherichia coli by using two compatible plasmids, resulting in strains with both OP degradation and OC degradation capabilities. To overcome the potential substrate uptake limitation, MPH was displayed on the cell surface of Escherichia coli using the N- and C-terminal domains of ice nucleation protein (INPNC) as an anchoring motif. The surface localization of INPNC-MPH was verified by cell fractionation, Western blot, proteinase accessibility, and immunofluorescence microscopy. Furthermore, both LinA and green fluorescent protein (GFP) were functionally co-expressed in the MPH-displaying Escherichia coli. The engineered Escherichia coli degraded OPs as well as OCs rapidly, and it can be easily monitored by GFP fluorescence.

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

    SciTech Connect

    Wang, Liming; Du, Dan; Lu, Donglai; Lin, Chiann Tso; Smith, Jordan N.; Timchalk, Charles; Liu, Fengquan; Wang, Jun; Lin, Yuehe

    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. With 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.

  17. Metabonomic analysis of quercetin against the toxicity of chronic exposure to a mixture of four organophosphate pesticides in rat plasma.

    PubMed

    Cao, Can; Zeng, Yan; Shi, Haidan; Yang, Shuang; Bao, Wei; Qi, Lei; Liu, Ying; Zhao, Xiujun

    2016-09-01

    1. A metabonomics approach was performed to investigate the effect of quercetin on the toxicity of chronic exposure to a mixture of four organophosphate pesticides (OPs) at their corresponding no-observed-adverse-effect level (NOAEL). The rats were divided into six groups (n = 10/group): control, two different doses of quercetin, OPs mixture and different doses of quercetin plus OPs mixture-treated groups. 2. Nine metabolites, including two quercetin metabolites and seven endogenous metabolites were identified in plasma. The intensities of metabolites significantly changed in the OP mixture-treated group compared with the control group (p < 0.01), such as lysoPE (16:0/0:0), lysoPC (17:0/0:0), lysoPC (15:0/0:0) and 4-pyridoxic acid, significantly increased; by contrast, the intensities of arachidonic acid and citric acid significantly decreased. Anomalous intensity changes in aforementioned metabolites were alleviated in the OP mixture plus 50 mg/kgċbw/d quercetin-treated group compared with the OP mixture-treated group (p < 0.05). 3. The results indicated that quercetin elicited partial protective effects against the toxicity induced by a mixture of OPs, which include regulation of lipid metabolism, improvement of tricarboxylic acid (TCA) cycle disorders, enhancement of antioxidant defence system to protect the liver.

  18. Use of biomarkers to indicate exposure of children to organophosphate pesticides: implications for a longitudinal study of children's environmental health.

    PubMed Central

    Wessels, Denise; Barr, Dana B; Mendola, Pauline

    2003-01-01

    Because of their history of widespread use in the United States and unknown long-term health effects, organophosphate pesticides (OPs) are being considered as a chemical class of interest in planning for the National Children's Study, a longitudinal study of children's environmental health. The availability and appropriate use of biomarkers to determine absorbed doses of environmental chemicals such as OPs are critical issues. Biomarkers of OP exposure are typically measured in blood and urine; however, postpartum meconium has been shown to be a promising matrix for assessing cumulative in utero exposure to the fetus, and studies are currently in progress to determine the utility of using saliva and amniotic fluid as matrices. In this article, we discuss the advantages and disadvantages of the currently available OP exposure monitoring methods (cholinesterase inhibition in blood, pesticides in blood, metabolites in urine and alternative matrices); study design issues for a large, long-term study of children's environmental health; and current research and future research needs. Because OPs are rapidly metabolized and excreted, the utility of one-time spot measurements of OP biomarkers is questionable unless background exposure levels are relatively stable over time or a specific time frame of interest for the study is identified and samples are collected accordingly. Biomarkers of OP exposure can be a valuable tool in epidemiology of children's environmental health, as long as they are applied and interpreted appropriately. PMID:14644670

  19. 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

  20. Prophylaxis against organophosphate poisoning by an enzyme hydrolysing organophosphorus compounds in mice.

    PubMed

    Ashani, Y; Rothschild, N; Segall, Y; Levanon, D; Raveh, L

    1991-01-01

    Parathion hydrolase purified from Pseudomonas sp. was injected i.v. into mice to demonstrate the feasibility of using organophosphorus acid anhydride (OPA) hydrolases as pretreatment against organophosphates (OP) poisoning. Results show that exogenous administration of as low as 7 to 26 micrograms of parathion hydrolase conferred protection against challenge with multiple median lethal doses (LD50) of diethyl p-nitrophenyl phosphate (paraoxon; 3.8-7.3 x LD50) and diethylfluorophosphate (DEFP; 2.9 x LD50) without administration of supportive drugs. The extent of protection observed was consistent with blood-parathion hydrolase levels and the kinetic constants of the enzymatic hydrolysis of paraoxon and DEFP by parathion hydrolase. OPA hydrolases not only appear to be potential prophylactic drugs capable of increasing survival ratio following OP intoxication but also to alleviate post-exposure symptoms.

  1. Pharmacokinetic Potentiation of Mixed Organophosphate and Pyrethroid Poison Leading to Prolonged Delayed Neuropathy

    PubMed Central

    Srinivasan, Meenakshi; Amin, Ruhul; Nagiri, Shivashankar Kaniyoor; Kudru, Chandrashekar Udyavara

    2016-01-01

    Organophosphate (OP) and mixed pesticide poisoning remains an important cause of hospital admission. Therefore, physician must be aware of atypical presentations of delayed neurological complications of poisoning by taking proper patient history. We report a case of a 23-year-old female who presented with high stepping gait and muscle wasting in hands. Patient history revealed consumption of approximately 4ml of mixed pesticide, consisting of 50% chlorpyrifos with synthetic pyrethroid, 5% cypermethrin. The prolonged and severe nature of delayed peripheral neuropathy, persisting at two years of follow-up, suggests that even small quantities of OP taken in combination with a pyrethroid can result in significant morbidity and is irreversible. PMID:28050396

  2. An organophosphate sensor based on photo-crosslinked hydrogel-entrapped E. coli.

    PubMed

    Fleischauer, Valerie; Heo, Jinseok

    2014-01-01

    This paper describes a whole cell sensor using E. coli entrapped within photocrosslinked hydrogel beads. Hydrogel beads containing organophosphorus hydrolase (OPH)-expressed E. coli were prepared by adding a hydrogel precursor solution containing the E. coli to an oil phase using a precision syringe pump, forming droplets, and photopolymerizing them. The beads showed good monodispersity with an average size of 1.2 mm. We detected organophosphates (OPs) using the beads. The detection relied on a pH-sensitive fluorescence dye that responds to protons produced from the intracellular OPH reaction with the OPs. This sensor could detect up to 80 μM of paraoxon with a detection limit of 3 μM. The enzyme activity of E. coli entrapped within the hydrogel beads showed stable enzyme activity for at least two weeks. This whole cell sensor will be implemented in a microfluidic system by directly photopolymerizing the hydrogel precursor solution within microfluidic channels.

  3. 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

  4. 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.

  5. 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

  6. Co-op

    SciTech Connect

    Nathan Barton, LLNL; Richard Becker, LLNL; Robert Chen, LLNL; Richard Hornung, LLNL; Jaroslaw Knap, LLNL; Gary Kumfert, LLNL; James Leek, LLNL; John May, LLNL; Miller, Patrick; Morrone, Chris; Tannahill, John

    2007-05-25

    Co-op is primarily middleware software, a runtime system for the support of the Cooperative Parallel Programming model. This model is based on using whole SPMD applications as components in a scalable programming, and having them treat one another as single objects and communicate via remote method invocation. Also included is some application level software: (1) a metric space database library for managing data items located in an arbitrary metric space and retrieving based on nearest neighbor queries; and (2) a Krieging extrapolation library for use in implementing adaptive sampling for generic multiscale simulations.

  7. A Model of Medical Countermeasures for Organophosphates

    DTIC Science & Technology

    2015-10-01

    Animal Data ................................................................. 51 6.2.1. Verifying AChE Activity...28 Table 5-2. Rate Constants for Three OPs Considered in the Animal Injury Model ..................... 29 Table 5...model OP injury and to be able to compare output to available animal data, we modeled the route of exposure for the OP. We account for three different

  8. 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

  9. Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999–2002

    PubMed Central

    Omoike, Ogbebor; Lewis, Ryan C.; Meeker, John D.

    2015-01-01

    Exposure to organophosphate (OP) insecticides may alter reproductive hormone levels in men and increase the risk for poor reductive health and other adverse health outcomes. However, relevant epidemiology studies in men are limited. We evaluated urinary concentrations of OP metabolites (3,5,6-trichloro-2-pyridinol and six dialkyl phosphates) in relation to serum concentrations of testosterone (T) and estradiol among 356 men aged 20–55 years old from the U.S. National Health and Nutrition Examination Survey. Biomarkers were detected in greater than 50% of the samples, except for diethyldithiophosphate, dimethylphosphate, and dimethyldithiophosphate. In adjusted regression models, we observed a statistically significant inverse relationship between diethyl phosphate (DEP) and T when DEP was modeled as either a continuous or categorical variable. These findings add to the limited evidence that exposure to certain OP insecticides is linked to altered T in men, which may have important implications for male health. PMID:25908234

  10. Novel nucleophiles enhance the human serum paraoxonase 1 (PON1)-mediated detoxication of organophosphates.

    PubMed

    Chambers, Janice E; Chambers, Howard W; Meek, Edward C; Funck, Kristen E; Bhavaraju, Manikanthan H; Gwaltney, Steven R; Pringle, Ronald B

    2015-01-01

    Paraoxonase 1 (PON1) is a calcium-dependent hydrolase associated with serum high-density lipoprotein particles. PON1 hydrolyzes some organophosphates (OPs), including some nerve agents, through nucleophilic attack of hydroxide ion (from water) in the active site. Most OPs are hydrolyzed inefficiently. This project seeks to identify nucleophiles that can enhance PON1-mediated OP degradation. A series of novel nucleophiles, substituted phenoxyalkyl pyridinium oximes, has been synthesized which enhance the degradation of surrogates of sarin (nitrophenyl isopropyl methylphosphonate; NIMP) and VX (nitrophenyl ethyl methylphosphonate; NEMP). Two types of in vitro assays have been conducted, a direct assay using millimolar concentrations of substrate with direct spectrophotometric quantitation of a hydrolysis product (4-nitrophenol) and an indirect assay using submicromolar concentrations of substrate with quantitation by the level of inhibition of an exogenous source of acetylcholinesterase from non-hydrolyzed substrate. Neither NIMP nor NEMP is hydrolyzed effectively by PON1 if one of these novel oximes is absent. However, in the presence of eight novel oximes, PON1-mediated degradation of both surrogates occurs. Computational modeling has created a model of PON1 embedded in phospholipid and has indicated general agreement of the binding enthalpies with the relative efficacy as PON1 enhancers. PON1 enhancement of degradation of OPs could be a unique and unprecedented mechanism of antidotal action.

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

    PubMed

    Golderman, Valery; Shavit-Stein, Efrat; Tamarin, Ilia; Rosman, Yossi; Shrot, Shai; Rosenberg, Nurit; Maggio, Nicola; Chapman, Joab; Eisenkraft, Arik

    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.

  12. 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.

  13. 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

  14. Creation of a protective pulmonary bioshield against inhaled organophosphates using an aerosolized bioscavenger.

    PubMed

    Rosenberg, Yvonne J; Fink, James B

    2016-06-01

    In addition to the global use of organophosphate (OP) pesticides for agriculture, OP nerve agents and pesticides have been employed on battlefields and by terrorists (e.g., a recent sarin attack in Syria). These occurrences highlight the need for an effective countermeasure against OP exposure. Human butyrylcholinesterase (HuBChE) is a leading candidate, but injection of the high doses required for protection present pharmacokinetic challenges. An aerosolized recombinant form (aer-rHuBChE) that can neutralize inhaled OPs at the portal of entry has been assessed for its efficacy in protecting macaques against respiratory toxicity following inhalation exposure to the pesticide paraoxon (aer-Px). While protection in macaques has been demonstrated using the MicroSprayer® delivery device, administration to humans will likely employ a vibrating mesh nebulizer (VMN). Compared to the 50-70% lung deposition achieved in adult humans with a VMN, deposition in macaques is <5%, an initial major obstacle to demonstrating protection. Such problems have been partly overcome by using a more efficient modified VMN and proportionally higher doses, which together generate an effective rHuBChE pulmonary bioshield and protect against high levels of inhaled Px.

  15. High-throughput screening system based on phenolics-responsive transcription activator for directed evolution of organophosphate-degrading enzymes.

    PubMed

    Jeong, Young-Su; Choi, Su-Lim; Kyeong, Hyun-Ho; Kim, Jin-Hyun; Kim, Eui-Joong; Pan, Jae-Gu; Rha, Eugene; Song, Jae Jun; Lee, Seung-Goo; Kim, Hak-Sung

    2012-11-01

    Synthetic organophosphates (OPs) have been used as nerve agents and pesticides due to their extreme toxicity and have caused serious environmental and human health problems. Hence, effective methods for detoxification and decontamination of OPs are of great significance. Here we constructed and used a high-throughput screening (HTS) system that was based on phenolics-responsive transcription activator for directed evolution of OP-degrading enzymes. In the screening system, phenolic compounds produced from substrates by OP-degrading enzymes bind a constitutively expressed transcription factor DmpR, initiating the expression of enhanced green fluorescent protein located at the downstream of the DmpR promoter. Fluorescence intensities of host cells are proportional to the levels of phenolic compounds, enabling the screening of OP-degrading enzymes with high catalytic activities by fluorescence-activated cell sorting. Methyl parathion hydrolase from Pseudomonas sp. WBC-3 and p-nitrophenyl diphenylphosphate were used as a model enzyme and an analogue of G-type nerve agents, respectively. The utility of the screening system was demonstrated by generating a triple mutant with a 100-fold higher k(cat)/K(m) than the wild-type enzyme after three rounds of directed evolution. The contributions of individual mutations to the catalytic efficiency were elucidated by mutational and structural analyses. The DmpR-based screening system is expected to be widely used for developing OP-degrading enzymes with greater potential.

  16. Cholinesterase reactivators: the fate and effects in the organism poisoned with organophosphates/nerve agents.

    PubMed

    Bajgar, J; Kuca, K; Jun, D; Bartosova, L; Fusek, J

    2007-12-01

    Understanding the mechanism of action of organophosphates (OP)/nerve agents -- irreversible acetylcholinesterase (AChE, EC 3.1.1.7) inhibition at the cholinergic synapses followed by metabolic dysbalance of the organism -- two therapeutic principles for antidotal treatment are derived. The main drugs are anticholinergics that antagonize the effects of accumulated acetylcholine at the cholinergic synapses and cholinesterase reactivators (oximes) reactivating inhibited AChE. Anticonvulsants such as diazepam are also used to treat convulsions. Though there are experimental data on a good therapeutic effects of reactivators, some attempts to underestimate the role of reactivators as effective antidotes against OP poisoning have been made. Some arguments on the necessity of their administration following OP poisoning are discussed. Their distribution patterns and some metabolic and pharmacological effects are described with the aim to resolve the question on their effective use, possible repeated administration in the treatment of OP poisoning, their peripheral and central effects including questions on their penetration through the blood brain barrier as well as a possibility to achieve their effective concentration for AChE reactivation in the brain. Reactivation of cholinesterases in the peripheral and central nervous system is described and it is underlined its importance for the survival or death of the organism poisoned with OP. Metabolization and some other effects of oximes (not connected with AChE reactivation) are discussed (e.g. forming of the phosphonylated oxime, parasympatholytic action, hepatotoxicity, behavioral changes etc.). An universality of oximes able to reactivate AChE inhibited by all OP is questioned and therefore, needs of development of new oximes is underlined.

  17. In vivo metabolism of organophosphate flame retardants and distribution of their main metabolites in adult zebrafish.

    PubMed

    Wang, Guowei; Chen, Hanyan; Du, Zhongkun; Li, Jianhua; Wang, Zunyao; Gao, Shixiang

    2017-07-15

    Understanding the metabolism of chemicals as well as the distribution and depuration of their main metabolites in tissues are essential for evaluating their fate and potential toxicity in vivo. Herein, we investigated the metabolism of six typical organophosphate (OP) flame retardants (tripropyl phosphate (TPRP), tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tri-p-cresyl phosphate (p-TCP)) in adult zebrafish in laboratory at three levels (0, 1/150 LC50 (environmentally relevant level), and 1/30 LC50 per OP analog). Twenty main metabolites were detected in the liver of OPs-exposed zebrafish using high resolution mass spectrometry (Q-TOF). The reaction pathways involving scission of the ester bond (hydrolysis), cleavage of the ether bond, oxidative hydroxylation, dechlorination, and coupling with glucuronic acid were proposed, and were further confirmed by the frontier electron density and point charge calculations. Tissue distribution of the twenty metabolites revealed that liver and intestine with the highest levels of metabolites were the most active organs for OPs biotransformation among the studied tissues of intestine, liver, roe, brain, muscle, and gill, which showed the importance of hepatobiliary system (liver-bile-intestine) in the metabolism and excretion of OPs in zebrafish. Fast depuration of metabolites from tissues indicated that the formed metabolites might be not persistent in fish, and easily released into water. This study provides comprehensive information on the metabolism of OPs in the tissue of zebrafish, which might give some hints for the exploration of their toxic mechanism in aquatic life.

  18. Acetylcholinesterase activity in Corbicula fluminea Mull., as a biomarker of organophosphate pesticide pollution in Pinacanauan River, Philippines.

    PubMed

    Beltran, Kimberly S; Pocsidio, Glorina N

    2010-06-01

    Organophosphates are known to inhibit the enzyme acetylcholinesterase. In this study, the AChE activity from the total soft tissues of Corbicula fluminea Mull. was used as a biomarker of organophosphate pollution in Pinacanauan River. Clams were collected from two different sites and at different seasons of the year. A colorimetric assay on the total soft tissues of the clams showed a directly proportional relationship between enzyme activity and condition of the riverine system. In vitro experiments on the total soft tissue, adductor muscles, digestive glands, and gills were conducted to assess the degree of localization of AChE as well as the sensitivity and tolerance of the enzymes in these tissues to varying concentrations of malathion. The degree of enzyme localization from highest to lowest is as follows: adductor muscle > gills > digestive gland whereas sensitivity to OP from greatest to least is: gills > adductor muscles > digestive gland.

  19. Recovery from ultra-high dose organophosphate poisoning after "in-the-field" antidote treatment: potential lessons for civil defense.

    PubMed

    Schrickel, Jan Wilko; Lewalter, Thorsten; Lüderitz, Berndt; Nickenig, Georg; Klehr, Hans-Ulrich; Rabe, Christian

    2009-10-01

    Organophosphate poisoning is associated with a high mortality rate due to respiratory failure, dysrhythmias, and multi-organ failure. We report two cases of survival after "in-the field" antidote treatment of very severe organophosphate poisonings. Two patients orally ingested large amounts of the organophosphorous agent oxydemeton-methyl in suicide attempts, resulting in the hypercholinergic syndrome in both. Resuscitation included early administration of antidote by emergency medical personnel as well as high-dose atropine. Plasma levels of pseudo cholinesterase were initially very low in both patients. Long-term mechanical ventilation was necessary, and both patients developed aspiration pneumonia. At discharge, no major neurological deficits were present. Prompt antidote treatment and aggressive supportive emergency and intensive care unit therapy contribute to improved survival after acute organophosphate poisoning. We believe that in cases of mass poisonings--for example, terrorist activity--therapy must be available on the scene as soon as possible. This also may require decentralized antidote storage.

  20. 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.

  1. Organophosphate nerve agent toxicity in Hydra attenuata.

    PubMed

    Lum, Karin T; Huebner, Henry J; Li, Yingchun; Phillips, Timothy D; Raushel, Frank M

    2003-08-01

    The toxicity for analogues of sarin (GB), soman (GD), and VX was evaluated using Hydra attenuata as a model organism. The organophosphate nerve agent analogue simulants used in this investigation included the following: isopropyl p-nitrophenyl methylphosphonate (for GB); pinacolyl p-nitrophenyl methylphosphonate (for GD); and diisopropyl S-(2-diisopropylaminoethyl)phosphorothioate, diethyl S-(2-diisopropylaminoethyl)phosphorothioate, and diethyl S-(2-trimethylaminoethyl)phosphorothioate (for VX). The toxicity of each organophosphate nerve agent was assessed quantitatively by measuring the minimal effective concentration within 92 h in H. attenuata. There is a positive correlation between the molecular hydrophobicity of the compound and its ability to cause toxicity. Results from this study indicate the potential for application of this assay in the field of organophosphate chemical warfare agent detection, as well as for the prediction of toxicity of structurally similar organophosphate compounds. The minimal effective concentration for two of the VX analogues was 2 orders of magnitude more toxic than the analogue for GD and 4 orders of magnitude more toxic than the analogue for GB.

  2. 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

  3. 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.

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

    PubMed

    Schmidt, Hayden R; Radić, Zoran; Taylor, Palmer; Fradinger, Erica A

    2015-04-15

    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 ki 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, kr, in both zebrafish and human AChE. However, differences between the Kox and k2 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, Ki and αKi, 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.

  5. Prenatal Exposure to Organophosphate Pesticides and Reciprocal Social Behavior in Childhood

    PubMed Central

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

    2014-01-01

    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 7–9 year 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 amongst 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. PMID:24934853

  6. Distribution and determinants of urinary biomarkers of exposure to organophosphate insecticides in Puerto Rican pregnant women

    PubMed Central

    Lewis, Ryan C.; Cantonwine, David E.; Anzalota Del Toro, Liza V.; Calafat, Antonia M.; Valentin-Blasini, Liza; Davis, Mark D.; Montesano, M. Angela; Alshawabkeh, Akram N.; Cordero, José F.

    2015-01-01

    Globally, human exposures to organophosphate (OP) insecticides may pose a significant burden to the health of mothers and their developing fetuses. Unfortunately, relevant data is limited in certain areas of the world concerning sources of exposure to OP insecticides in pregnant populations. To begin to address this gap in information for Puerto Rico, we studied repeated measures of urinary concentrations of 10 OP insecticide metabolites among 54 pregnant women from the northern karst region of the island. We also collected demographic data and self-reported information on the consumption of fruits, vegetables, and legumes in the past 48-hr before urine collection and home pest-related issues. We calculated the distributions of the urinary biomarkers and compared them to women of reproductive age from the general U.S. population. We also used statistical models accounting for correlated data to assess within-subject temporal variability of the urinary biomarkers and to identify predictors of exposure. We found that for all but two metabolites (para-nitrophenol [PNP], diethylthiophosphate [DETP]), 50th or 95th percentile urinary concentrations (the metric that was used for comparison was based on the biomarker’s detection frequency) of the other eight metabolites (3,5,6-trichloro-2-pyridinol [TCPY], 2-isopropyl-4-methyl-6-hydroxy-pyrimidine, malathion dicarboxylic acid, diethylphosphate, diethyldithiophosphate, dimethylphosphate, dimethylthiophosphate [DMTP], dimethyldithiophosphate) were somewhat lower in our cohort compared with similarly aged women from the continental United States. TCPY, PNP, DETP, and DMTP, which were the only urinary metabolites detected in greater than 50% of the samples, had poor reproducibility (intraclass correlation coefficient range: 0.19–0.28) during pregnancy. Positive predictors of OP insecticide exposure included: age; marital or employment status; consumption of cherries, grape juice, peanuts, peanut butter, or raisins; and

  7. Occurrence and distribution of organophosphate flame retardants/plasticizers in wastewater treatment plant sludges from the Pearl River Delta, China.

    PubMed

    Zeng, Xiangying; He, Lixiong; Cao, Shuxia; Ma, Shengtao; Yu, Zhiqiang; Gui, Hongyan; Sheng, Guoying; Fu, Jiamo

    2014-08-01

    Organophosphate esters (OPs) are widely used as flame retardants or plasticizers and are ubiquitously distributed in the environment. In the present study, the occurrence and distribution of 7 widely used OPs were analyzed in sludge samples collected from 19 municipal wastewater treatment plants in the Pearl River Delta, South China. All analytes were detected in these samples, and the total concentration of OPs ranged from 96.7 µg/kg to 1312.9 µg/kg dry weight, with a mean value of 420.1 µg/kg dry weight. In most sludge samples OPs exhibited a similar distribution pattern, for example, tris(2-butoxyethyl) phosphate (TBEP) and triphenyl phosphate (TPhP) were identified as the dominant compounds. However, the results also indicated significantly higher levels of OPs in specific sludges, such as tri-n-butyl phosphate (804.9 µg/kg), TBEP (783.7 µg/kg), TPhP (656.7 µg/kg), and tritolyl phosphate (265.0 µg/kg), which implied different discharge sources in the studied areas.

  8. 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

  9. Case report: an unusual heart rhythm associated with organophosphate poisoning.

    PubMed

    Gul, Enes Elvin; Can, Ilknur; Kusumoto, Fred M

    2012-09-01

    Organophosphate pesticides have emerged as a common cause of poisoning, particularly in developing countries. The most common electrocardiographic abnormalities observed in organophosphate poisoning are sinus tachycardia, QT interval prolongation, and, very rarely, ventricular arrhythmias. We report a case of organophosphate poisoning associated with atrial fibrillation, right bundle branch block, QT interval prolongation, and intermittent narrow QRS complexes that were most likely due to automaticity from the region of the left posterior fascicle.

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

    PubMed Central

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

    2012-01-01

    Background 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. Methods 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. Results Diethylalkylphosphates (DEAP) and dimethylalkylphosphates (DMAP) were detected in urine in 76% and 27% of 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). Conclusions Urinary DAP levels in Chilean school children were high compared previously reported studies. The presence of chlorpyrifos and phosmet residues in fruits was the major factor predicting urinary DAP metabolite concentrations in children. PMID:22732215

  11. Detection and classification of organophosphate nerve agent simulants using support vector machines with multiarray sensors.

    PubMed

    Sadik, Omowunmi; Land, Walker H; Wanekaya, Adam K; Uematsu, Michiko; Embrechts, Mark J; Wong, Lut; Leibensperger, Dale; Volykin, Alex

    2004-01-01

    The need for rapid and accurate detection systems is expanding and the utilization of cross-reactive sensor arrays to detect chemical warfare agents in conjunction with novel computational techniques may prove to be a potential solution to this challenge. We have investigated the detection, prediction, and classification of various organophosphate (OP) nerve agent simulants using sensor arrays with a novel learning scheme known as support vector machines (SVMs). The OPs tested include parathion, malathion, dichlorvos, trichlorfon, paraoxon, and diazinon. A new data reduction software program was written in MATLAB V. 6.1 to extract steady-state and kinetic data from the sensor arrays. The program also creates training sets by mixing and randomly sorting any combination of data categories into both positive and negative cases. The resulting signals were fed into SVM software for "pairwise" and "one" vs all classification. Experimental results for this new paradigm show a significant increase in classification accuracy when compared to artificial neural networks (ANNs). Three kernels, the S2000, the polynomial, and the Gaussian radial basis function (RBF), were tested and compared to the ANN. The following measures of performance were considered in the pairwise classification: receiver operating curve (ROC) Az indices, specificities, and positive predictive values (PPVs). The ROC Az) values, specifities, and PPVs increases ranged from 5% to 25%, 108% to 204%, and 13% to 54%, respectively, in all OP pairs studied when compared to the ANN baseline. Dichlorvos, trichlorfon, and paraoxon were perfectly predicted. Positive prediction for malathion was 95%.

  12. Creation of catalytic antibodies metabolizing organophosphate compounds.

    PubMed

    Kurkova, I N; Smirnov, I V; Belogurov, A A; Ponomarenko, N A; Gabibov, A G

    2012-10-01

    Development of new ways of creating catalytic antibodies possessing defined substrate specificity towards artificial substrates has important fundamental and practical aspects. Low immunogenicity combined with high stability of immunoglobulins in the blood stream makes abzymes potent remedies. A good example is the cocaine-hydrolyzing antibody that has successfully passed clinical trials. Creation of an effective antidote against organophosphate compounds, which are very toxic substances, is a very realistic goal. The most promising antidotes are based on cholinesterases. These antidotes are now expensive, and their production methods are inefficient. Recombinant antibodies are widely applied in clinics and have some advantage compared to enzymatic drugs. A new potential abzyme antidote will combine effective catalysis comparable to enzymes with high stability and the ability to switch on effector mechanisms specific for antibodies. Examples of abzymes metabolizing organophosphate substrates are discussed in this review.

  13. 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.

  14. The occurrence and removal of organophosphate ester flame retardants/plasticizers in a municipal wastewater treatment plant in the Pearl River Delta, China.

    PubMed

    Zeng, Xiangying; Liu, Zhiyang; He, Lixiong; Cao, Shuxia; Song, Han; Yu, Zhiqiang; Sheng, Guoying; Fu, Jiamo

    2015-01-01

    The occurrence, distribution and main removal pathway of seven widely used organophosphate esters (OPs) in a municipal wastewater treatment plant (WWTP) located in the Pearl River Delta were investigated. Their daily discharge load into the Pearl River via effluent was also estimated. All the target analytes were detected in wastewater, suspended particle and dewatered sludge, with tri-n-butyl phosphate (TBP) and tris(2-butoxyethyl) phosphate (TBEP) as the main components. The total concentrations of TBP and TBEP were 21271.8 ng L(-1) and 4349.4 ng L(-1), 3105.1 ng L(-1) and 494.5 ng L(-1) in influent wastewater and final effluent, respectively. These results indicated that non-chlorinated OPs were removed efficiently in the WWTP, while chlorinated OPs passed through the WWTP unchanged due to their resistance to current wastewater treatment technology. Approximate 91.4 g of non-chlorinated OPs and 23.4 g of chlorinated OPs per day were discharged into the Pearl River via effluent, 2.4 g of non-chlorinated OPs and 0.6 g of chlorinated OPs entered the environment following sludge disposal.

  15. Organophosphate nerve agent detection with europium complexes.

    PubMed

    Schwierking, Jake R; Menzel, Laird W; Menzel, E Roland

    2004-11-05

    We explore the detection of paraoxon, a model compound for nonvolatile organophosphate nerve agents such as VX. The detection utilizes europium complexes with 1,10 phenanthroline and thenoyltrifluoroacetone as sensitizing ligands. Both europium luminescence quenching and luminescence enhancement modalities are involved in the detection, which is simple, rapid, and sensitive. It is adaptable as well to the more volatile fluorophosphate nerve agents. It involves nothing more than visual luminescence observation under sample illumination by an ordinary hand-held ultraviolet lamp.

  16. Relationship Between Organophosphate Toxicity and Choline Metabolism

    DTIC Science & Technology

    1986-06-06

    Effects of the Organophosphates on the Activity of Phospholipase A2 in a Crude Mitochondrial Fraction from Striatumn 43 LIST OF FIGURES Figure I...Activity of Phospholipase A2 in a Crude Mitochondrial Fraction from Rat Striatum 41 8 1I Figure 7. Effects of DFP on the Postmortem Accumulation of...Accumulation of Choline in the Siaitu and Hippocampus 47 Figure 11. Effects of Chronic Paraoxon Adrninis,,ation on the Development of a Myopathy in Rat

  17. Does organophosphate poisoning cause cardiac injury?

    PubMed

    Aghabiklooei, Abbas; Mostafazadeh, Babak; Farzaneh, Esmaeil; Morteza, Afsaneh

    2013-11-01

    Organophosphates are insecticides which are widely used as a suicidal agent in Iran. They are associated with different types of cardiac complications including cardiac arrest and arrhythmia, however their role in cardiac injury is not known yet. The aim of this study was to investigate the presence of myocardial damage in patients with cholinesterase poisoning.It was a prospective study conducted from January 2008 to March 2010. Cohorts of patients with cholinesterase poisoning due to suicidal attempt who have been referred to Loghman hospital were selected. Patients who have taken more than one poison or were used concomitant drugs were excluded. Physical examination was performed on admission to discover warning sign. Peripheral arterial blood gases, creatine kinase, creatine kinase-myocardial band, troponin-T measurements were performed in all cases. There were 24 patients, 7 of them women, with the mean age of 41.2±15.05 who were included in this study. Non-survivors had significantly higher levels of systolic blood pressure, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide, bicarbonate Glasgow Coma Scale scoring and longer duration of mechanical ventilation. Our findings showed that cardiac injury is an important cause of death in organophosphate poisoning. It could be hypothesized that cardiac injury is a strong predictor of death in patients with organophosphate poisoning.

  18. [Interest in an glutamate antagonistic compound for the treatment of organophosphate poisoning].

    PubMed

    Lallement, G

    2000-01-01

    Classical emergency treatment of organophosphate poisoning includes the combined administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). In subjects taking pyridostigmine and trained to autoadminister at least one autoinjector at the first signs of poisoning, classical emergency treatment ensures survival but only an antiglutamatergic compound like gacyclidine appears to be able to ensure optimal management of nerve agent poisoning in terms of rapid normalization of EEG activity, clinical recovery and total neuroprotection. All of this reinforces the therapeutical value of gacyclidine, which is in the process of approval for human use in France for treatment of head injury, as a central nervous system protective agent for the treatment of OP poisoning.

  19. Application of graphene for preconcentration and highly sensitive stripping voltammetric analysis of organophosphate pesticide.

    PubMed

    Wu, Shuo; Lan, Xiaoqin; Cui, Lijun; Zhang, Lihui; Tao, Shengyang; Wang, Hainan; Han, Mei; Liu, Zhiguang; Meng, Changgong

    2011-08-12

    Electrochemical reduced β-cyclodextrin dispersed graphene (β-CD-graphene) was developed as a sorbent for the preconcentration and electrochemical sensing of methyl parathion (MP), a representative nitroaromatic organophosphate pesticide with good redox activity. Benefited from the ultra-large surface area, large delocalized π-electron system and the superconductivity of β-CD-graphene, large amount of MP could be extracted on β-CD-graphene modified electrode via strong π-π interaction and exhibited fast accumulation and electron transfer rate. Combined with differential pulse voltammetric analysis, the sensor shows ultra-high sensitivity, good selectivity and fast response. The limit of detection of 0.05 ppb is more than 10 times lower than those obtained from other sorbent based sensors. The method may open up a new possibility for the widespread use of electrochemical sensors for monitoring of ultra-trace OPs.

  20. Developments in alternative treatments for organophosphate poisoning.

    PubMed

    Iyer, Rupa; Iken, Brian; Leon, Alex

    2015-03-04

    Organophosphosphates (OPs) are highly effective acetylcholinesterase (AChE) inhibitors that are used worldwide as cheap, multi-purpose insecticides. OPs are also used as chemical weapons forming the active core of G-series and V-series chemical agents including tabun, sarin, soman, cyclosarin, VX, and their chemical analogs. Human exposure to any of these compounds leads to neurotoxic accumulation of the neurotransmitter acetylcholine, resulting in abnormal nerve function and multiple secondary health complications. Suicide from deliberate exposure to OPs is particularly prevalent in developing countries across the world and constitutes a major global health crisis. The prevalence and accessible nature of OP compounds within modern agricultural spheres and concern over their potential use in biochemical weapon attacks have incentivized both government agencies and medical researchers to enact stricter regulatory policies over their usage and to begin developing more proactive medical treatments in cases of OP poisoning. This review will discuss the research undertaken in recent years that has investigated new supplementary drug options for OP treatment and support therapy, including progress in the development of enzymatic prophylaxis.

  1. 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...

  2. Abnormal Spontaneous Eye Movements as Initial Presentation of Organophosphate Poisoning

    PubMed Central

    De Lima Teixeira, Igor; Bazan, Silméia Garcia Zanati; Schelp, Arthur Oscar; Luvizutto, Gustavo José; De Lima, Fabrício Diniz; Bazan, Rodrigo

    2017-01-01

    Background Atypical ocular bobbing may result from an intentional poisoning from an organophosphate compound. Phenomenology Shown The patient exhibited conjugated, slow, arrhythmic, unpredictable eye movements in all directions, diagnosed as atypical ocular bobbing. Educational Value This is a rare, well‐documented, clinically relevant case for medical students for correct diagnosis and appropriate treatment of organophosphate intoxication. PMID:28243486

  3. 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.

  4. A Novel Fluorine-18 β-Fluoroethoxy Organophosphate Positron Emission Tomography Imaging Tracer Targeted to Central Nervous System Acetylcholinesterase

    PubMed Central

    2014-01-01

    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 [18F]prosthetic group coupling approach. The imaging utility of the [18F]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 [18F]tracer studies are ongoing to exploit the technology to dynamically probe organophosphate mechanisms of action in mammalian live tissues. PMID:24716794

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

    PubMed Central

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

    2017-01-01

    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. PMID:28195202

  6. Organophosphate Hydrolase in Conductometric Biosensor for the Detection of Organophosphate Pesticides

    PubMed Central

    Mulyasuryani, Ani; Prasetyawan, Sasangka

    2015-01-01

    The research has developed an enzyme biosensor for the detection organophosphate pesticide residues. The biosensor consists of a pair of screen-printed carbon electrode (SPCEs). One of electrodes contains immobilized organophosphate hydrolase (OPH) on a chitosan membrane by cross-linking it with glutaraldehyde. The area of the electrodes was optimized to 3, 5, and 7 mm2. The OPH was isolated from Pseudomonas putida, and was purified by the ammonium sulfate precipitation method, with 6444 ppm (A) and 7865 ppm (B). The organophosphate pesticide samples were 0–100 ppb in tris-acetate buffer 0.05 M, pH 8.5. The results showed that the best performance of the biosensor was achieved by the enzyme A with an electrode area of 5 mm2. The sensitivity of the biosensor was between 3 and 32 µS/ppb, and the detection limit for the organophosphate pesticides was 40 ppb (diazinon), 30 ppb (malathion), 20 ppb (chlorpyrifos), and 40 ppm (profenofos). PMID:26483607

  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. 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

  9. The organophosphate sarin, at low concentrations, inhibits the evoked release of GABA in rat hippocampal slices.

    PubMed

    Chebabo, S R; Santos, M D; Albuquerque, E X

    1999-12-01

    In the present study, the whole-cell mode of the patch-clamp technique was applied to neurons of the CA1 pyramidal layer of rat hippocampal slices to investigate the effects of the organophosphate (OP) sarin on field stimulation-evoked and on tetrodotoxin (TTX)-insensitive postsynaptic currents (PSCs) mediated by activation of type A gamma-aminobutyric acid (GABA) receptors or AMPA-type glutamate receptors. At 0.3-1 nM, sarin reduced the amplitude of GABA-mediated PSCs and had no effect on the amplitude of glutamatergic PSCs evoked by field stimulation of neurons synaptically connected to the neuron under study. The effect of sarin on evoked GABAergic PSCs was unrelated to cholinesterase inhibition, was partially reversed upon washing of the neurons with sarin-free external solution, and was mediated by a direct interaction of the OP with muscarinic acetylcholine receptors present on presynaptic GABAergic neurons. Sarin had no effect on the amplitude or kinetics of GABA- or glutamate-mediated miniature postsynaptic currents (MPSCs) recorded in the presence of the Na+-channel blocker TTX (300 nM), indicating that the OP does not interact with GABA(A) or glutamate receptors. Further, sarin did not alter the frequency of GABAergic or glutamatergic MPSCs, a finding that led to the conclusion that this OP does not affect the TTX-insensitive release of neurotransmitters. A selective reduction by sarin of the action potential-dependent release of GABA in the hippocampus can account for the occurrence of seizures in intoxicated subjects.

  10. CATALYTIC DETOXIFICATION OF NERVE AGENT AND PESTICIDE ORGANOPHOSPHATES BY BUTYRYLCHOLINESTERASE ASSISTED WITH NON-PYRIDINIUM OXIMES

    PubMed Central

    Radić, Zoran; Dale, Trevor; Kovarik, Zrinka; Berend, Suzana; Garcia, Edzna; Zhang, Limin; Amitai, Gabriel; Green, Carol; Radić, Božica; Duggan, Brendan M.; Ajami, Dariush; Rebek, Julius; Taylor, Palmer

    2016-01-01

    SYNOPSIS We present here a comprehensive in vitro, ex vivo and in vivo study on hydrolytic detoxification of nerve agent and pesticide organophosphates (OPs) catalyzed by purified human butyrylcholinesterase (hBChE) in combination with novel non-pyridinium oxime reactivators. We identified 2-trimethylammonio-6-hydroxybenzaldehyde oxime (TAB2OH) as an efficient reactivator of OP-hBChE conjugates formed by the nerve agents, VX and cyclosarin, and the pesticide, paraoxon. It was also functional in reactivation of sarin and tabun inhibited hBChE. A three to five-fold enhancement of in vitro reactivation of VX, cyclosarin and paraoxon inhibited hBChE was observed, when compared to the commonly used N-methylpyridinium aldoxime reactivator, 2PAM. Kinetic analysis showed the enhancement resulted from improved molecular recognition of corresponding OP-hBChE conjugates by TAB2OH. The unique features of TAB2OH stem from an exocyclic quaternary nitrogen and a hydroxyl, both ortho to an oxime group on a benzene ring. pH dependences reveal participation of the hydroxyl (pKa=7.6) forming an additional ionizing nucleophile to potentiate the oxime (pKa=10) at physiological pH. The TAB2OH protective indices in therapy of sarin and paraoxon exposed mice were enhanced by 30% – 60% when they were treated with a combination of TAB2OH and sub-stoichiometric hBChE. These results establish that oxime-assisted catalysis is feasible for OP bioscavenging. PMID:23216060

  11. 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

  12. 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.

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

    SciTech Connect

    Liu, Guodong; Wang, Jun; Barry, Richard C.; Petersen, Catherine E.; Timchalk, Charles; Gassman, Paul L.; Lin, Yuehe

    2008-11-01

    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 electrochemical 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.

  14. Detoxification of organophosphate nerve agents by bacterial phosphotriesterase

    SciTech Connect

    Ghanem, Eman; Raushel, Frank M. . E-mail: raushel@tamu.edu

    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 utilized 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.

  15. Occurrence and distribution of organophosphate triesters and diesters in sludge from sewage treatment plants of Beijing, China.

    PubMed

    Gao, Lihong; Shi, Yali; Li, Wenhui; Liu, Jiemin; Cai, Yaqi

    2016-02-15

    The occurrence and distribution of 14 organophosphate (OP) triesters and 5 diesters were investigated in sludge from eight sewage treatment plants (STPs) in Beijing, China, during 2008-2014. Tri(2-ethylhexyl) phosphate (TEHP) and tri-m-cresyl phosphate (TCrP) were the predominant triesters with the average concentration of 233-137 μg/kg, respectively. Also, the polar and hydrophilic trimethyl phosphate (TMP) and triethyl phosphate (TEP) were detected in 19% and 74% of sludge samples, respectively. Three of five diesters were detected in sludge samples, and di(2-ethylhexyl) phosphate (DEHP) revealed the highest average concentration of 96.0 μg/kg, followed by diphenyl phosphate (DPhP, 18.0 μg/kg). The levels of OP triesters in sludge varied with the compositions of the sewage and treatment capacity of STPs, as well as the adjacent sources. In comparison with that in the former years, relatively higher concentration of total OP triesters in sludge was observed in 2014, which is consistent with the rapid growth in consumption of these chemicals in China. Finally, environmental risk assessment indicated potential harmful effects of OP triesters on soil microorganisms after sludge landfill or fertilization.

  16. Organophosphate Pesticide Exposure in School-Aged Children Living in Rice and Aquacultural Farming Regions of Thailand

    PubMed Central

    Rohitrattana, Juthasiri; Siriwong, Wattasit; Tunsaringkarn, Tanasorn; Panuwet, Parinya; Ryan, P. Barry; Barr, Dana Boyd; Robson, Mark G.; Fiedler, Nancy

    2015-01-01

    Organophosphate pesticides (OPs) are widely used in agricultural sectors in Thailand. Previous studies have documented that children residing in agricultural areas have higher exposure to OPs than children living in other residential areas. The objective of this study was to quantify urinary biomarkers of OP exposure and determine the environmental conditions and activities that predict their levels among children living in Central Thailand farming regions. In October 2011, 53 6–8-year-old participants were recruited from Pathum Thani Province, Thailand. Twenty-four lived in rice farming communities at Khlong Luang District where OPs are the pesticides used frequently. Twenty-nine participants, living in aquacultural farming communities at Lum Luk Ka District where OPs are not used, were recruited to serve as controls for pathways of exposure (e.g., residential, dietary) other than occupational/paraoccupational exposures encountered in rice farming. Household environments and participants’ activities were assessed using a parental structured interview. Urine samples (first morning voids) were collected from participants for OP urinary metabolite (i.e., dialkylphosphates [DAPs] and 3,5,6-trichloro-2-pyridinol [TCPy]) measurements. The levels of most urinary OP metabolites were significantly higher in participants who lived in a rice farming community than those who lived in an aquacultural farming community (P < .05). The results from linear regression analysis revealed that the frequency of OP application on rice farms (}.DAP: P = .001; TCPy: P = .001) and living in a rice farming community (}.DAP: P = .009; TCPy: P < .001) were significant predictors of urinary DAP metabolite levels in participants. Increasing TCPy levels were significantly related to proximity to rice farm (P = .03), being with parent while working on a farm (P = .02), playing on a farm (P = .03), and the presence of observable dirt accumulated on the child's body (P = .02). In conclusion, OP

  17. Organophosphate pesticide exposure in school-aged children living in rice and aquacultural farming regions of Thailand.

    PubMed

    Rohitrattana, Juthasiri; Siriwong, Wattasit; Tunsaringkarn, Tanasorn; Panuwet, Parinya; Ryan, P Barry; Barr, Dana Boyd; Robson, Mark G; Fiedler, Nancy

    2014-01-01

    Organophosphate pesticides (OPs) are widely used in agricultural sectors in Thailand. Previous studies have documented that children residing in agricultural areas have higher exposure to OPs than children living in other residential areas. The objective of this study was to quantify urinary biomarkers of OP exposure and determine the environmental conditions and activities that predict their levels among children living in Central Thailand farming regions. In October 2011, 53 6-8-year-old participants were recruited from Pathum Thani Province, Thailand. Twenty-four lived in rice farming communities at Khlong Luang District where OPs are the pesticides used frequently. Twenty-nine participants, living in aquacultural farming communities at Lum Luk Ka District where OPs are not used, were recruited to serve as controls for pathways of exposure (e.g., residential, dietary) other than occupational/paraoccupational exposures encountered in rice farming. Household environments and participants' activities were assessed using a parental structured interview. Urine samples (first morning voids) were collected from participants for OP urinary metabolite (i.e., dialkylphosphates [DAPs] and 3,5,6-trichloro-2-pyridinol [TCPy]) measurements. The levels of most urinary OP metabolites were significantly higher in participants who lived in a rice farming community than those who lived in an aquacultural farming community (P < .05). The results from linear regression analysis revealed that the frequency of OP application on rice farms (∑DAP: P = .001; TCPy: P = .001) and living in a rice farming community (∑DAP: P = .009; TCPy: P < .001) were significant predictors of urinary DAP metabolite levels in participants. Increasing TCPy levels were significantly related to proximity to rice farm (P = .03), being with parent while working on a farm (P = .02), playing on a farm (P = .03), and the presence of observable dirt accumulated on the child's body (P = .02). In conclusion, OP

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

    SciTech Connect

    Read, David J.; Li Yong; Chao, Moses V.; Cavanagh, John B.; Glynn, Paul

    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 may 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.

  19. Interethnic variability of plasma paraoxonase (PON1) activity towards organophosphates and PON1 polymorphisms among Asian populations--a short review.

    PubMed

    Mohamed Ali, Safiyya; Chia, Sin Eng

    2008-08-01

    Organophosphate (OP) poisoning is a progressively worrying phenomenon as worldwide pesticide production and consumption has doubled. On average, WHO estimates that 3% of agricultural workers in developing Asian countries suffer an episode of pesticide poisoning every year. Furthermore, the threat of OP usage in terrorism is existent, as seen by the subway tragedy in Tokyo in 1995 where sarin was used. Despite these alarming facts, there is currently no global system to track poisonings related to pesticide use. Human serum paraoxonase (PON1) is the enzyme that hydrolyses OP compounds. Serum PON1 levels and activity vary widely among different ethnic populations. Two commonly studied polymorphisms of PON1 are PON1Q192R and PON1L55M. PON1R192 hydrolyses paraoxon faster than PON1Q192 but hydrolyses diazoxon, sarin and soman eight times slower, and vice versa. PON1M55 has lower plasma levels of PON1 than PON1L55. As the prevalence of the different alleles and genotypic distribution vary between the Asian populations we studied, we propose the necessity to study PON1 polymorphisms and its role in OP toxicity in Asian populations. This would help safeguard the proper care of agricultural workers who might be affected by OP poisoning, and alert relevant anti biological terrorism agencies on possible risks involved in the event of an OP attack and provide effective counter measures.

  20. 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.

  1. 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.

  2. 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).

  3. Development of enzyme-based biosensors for the detection of organophosphate neurotoxins

    NASA Astrophysics Data System (ADS)

    Paliwal, Sheetal

    Elevated concerns of ecological safety and environmental pollution have facilitated massive research in the area of chemical and biological agent detection. Large numbers of anthropogenic chemicals were introduced in the environment within last 50 years, which posed a serious threat to the natural ecological balance. The series of unfortunate events in the past could have been avoided or minimized by the availability of adequately selective and sensitive detectors, capable of discriminating between common use pesticides and chemical warfare agents. Organophosphates (OPs) in particular are more of a concern because of their toxicity and inhibition of esterase enzymes which are involved in nerve transmission. They have been an integral part of agricultural industry for past decades owing to their specificity. In addition, to their wide usage, they have also been exploited for the development of chemical warfare agents. Consequently, there is an emergent need for rapid and sensitive detection methods. Enzyme-based studies have been investigated in an effort to develop simple, rapid, user-friendly and sensitive detection of OPs. The methods described have been developed using OPH, an enzyme capable of hydrolyzing OPs. A rapid detection method using a fiber-optic waveguide and a portable fluorimeter Analyte 2000 was developed. Immobilization of OPH was accomplished using avidin-biotin chemistry. Change in fluorescence intensity was observed upon hydrolysis of substrate by OPH, concentration as low as 0.05 muM paraoxon (PX) was qualitatively measured. A novel detection method for p-nitrophenol and p-nitrophenyl substituent OPs based on fluorescence quenching of coumarin1, a dye similar in structure to some OPs have also been developed. Decrease in fluorescence intensity of coumarin1 was proportional to paraoxon concentration in the range of 0.7--170 muM. To preserve OPH activity and stability, encapsulation using lysozyme-mediated silica nanoparticles was accomplished

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

    SciTech Connect

    Schmidt, Hayden R.; Radić, Zoran; Taylor, Palmer; Fradinger, Erica A.

    2015-04-15

    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 the 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 and not

  5. 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.

  6. 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.

  7. 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

    2016-10-06

    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.

  8. 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.

  9. Organophosphate Pesticide Exposure and Work in Pome Fruit: Evidence for the Take-Home Pesticide Pathway

    PubMed Central

    Coronado, Gloria D.; Vigoren, Eric M.; Thompson, Beti; Griffith, William C.; Faustman, Elaine M.

    2006-01-01

    Organophosphate (OP) pesticides are commonly used in the United States, and farmworkers are at risk for chronic exposure. Using a sample of 218 farmworkers in 24 communities and labor camps in eastern Washington State, we examined the association between agricultural crop and OP pesticide metabolite concentrations in urine samples of adult farmworkers and their children and OP pesticide residues in house and vehicle dust samples. Commonly reported crops were apples (71.6%), cherries (59.6%), pears (37.2%), grapes (27.1%), hops (22.9%), and peaches (12.4%). Crops were grouped into two main categories: pome fruits (apples and pears) and non-pome fruits. Farmworkers who worked in the pome fruits had significantly higher concentrations of dimethyl pesticide metabolites in their urine and elevated azinphos-methyl concentrations in their homes and vehicles than workers who did not work in these crops. Among pome-fruit workers, those who worked in both apples and pears had higher urinary metabolites concentrations and pesticide residue concentrations in dust than did those who worked in a single pome fruit. Children living in households with pome-fruit workers were found to have higher concentrations of urinary dimethyl metabolites than did children of non-pome-fruit workers. Adult urinary concentrations showed significant correlations with both the vehicle and house-dust azinphos-methyl concentrations, and child urinary concentrations were correlated significantly with adult urinary concentrations and with the house-dust azinphos-methyl concentration. The results provide support for the take-home pathway of pesticide exposure and show an association between measures of pesticide exposure and the number of pome-fruit crops worked by farmworkers. PMID:16835050

  10. 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

  11. 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

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

    SciTech Connect

    Nomura, Daniel K.; Fujioka, Kazutoshi; Issa, Roger S.; Ward, Anna M.; Cravatt, Benjamin F.; Casida, John E.

    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 there 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.

  13. Amitraz: a mimicker of organophosphate poisoning.

    PubMed

    Dhooria, Sahajal; Behera, Digambar; Agarwal, Ritesh

    2015-10-01

    Amitraz is used as an ectoparasiticide for dogs and cattle. Human poisoning due to amitraz may be misdiagnosed as organophosphate/carbamate (OPC) toxicity, since amitraz poisoning shares several clinical features (miosis, bradycardia and hypotension) encountered with OPC poisoning. A 19-year-old man with an alleged history of suicidal ingestion of a pesticide presented with drowsiness and was found to have constricted pupils, hypotension and bradycardia. He was diagnosed as a case of OPC poisoning and was treated with atropine and pralidoxime prior to presentation to our centre. Absence of a hypersecretory state, and the presence of hyperglycaemia and hypothermia along with a normal serum cholinesterase level suggested an alternate possibility. Retrieval of the poison container confirmed the diagnosis of amitraz poisoning. The patient made a rapid recovery with supportive management. Clinician awareness is key to successful management of this poisoning, which carries a good prognosis.

  14. Transient Distal Renal Tubular Acidosis in Organophosphate Poisoning

    PubMed Central

    Narayan, Ram; Abdulla, Mansoor C.; Alungal, Jemshad

    2017-01-01

    Renal complications due to organophosphate poisoning are very rare. We are presenting a unique case of transient distal renal tubular acidosis due to organophosphate poisoning, which to the best of our knowledge is the first of its kind. An elderly female after deliberate self-harm with ingestion of chlorpyrifos had multiple ventricular arrhythmias due to hypokalemia secondary to distal renal tubular acidosis which improved completely after treatment.

  15. Biosensor for Continuous Monitoring of Organophosphate Aerosols (Preprint)

    DTIC Science & Technology

    2006-12-01

    of a range of organophosphates inclnding paraoxon, demeton-S and malathion . The detection limits ofthe Ev1ERs for specific organophosphates are...pesticides such as parathion and malathion and chemical warfare agents such as soman, sarin and VX (Dumas et al., 1989; Di Sioudi et cl.. 1Q99...continuously at 412 run for malathion and demeton-S and 400 11m for paraoxon. Ellman’s reagent within the mobile phase reacts with free thiols generated

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

    SciTech Connect

    Singh, Satyender; Kumar, Vivek; Thakur, Sachin; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Ichhpujani, Rattan Lal; Rai, Arvind

    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 results 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 (p < 0

  17. Exposure characterization of three major insecticide lines in urine of young children in Japan-neonicotinoids, organophosphates, and pyrethroids.

    PubMed

    Osaka, Aya; Ueyama, Jun; Kondo, Takaaki; Nomura, Hiroshi; Sugiura, Yuka; Saito, Isao; Nakane, Kunihiko; Takaishi, Ayuko; Ogi, Hiroko; Wakusawa, Shinya; Ito, Yuki; Kamijima, Michihiro

    2016-05-01

    The use of neonicotinoid (NEO) insecticides has increased over the past decade not only in Japan but also worldwide, while organophosphate (OP) and pyrethroid (PYR) insecticides are still conventionally used in agriculture and domestic pest control. However, limited data are currently available on the NEO exposure levels, especially in children, who are particularly vulnerable to environmental toxicants. Thus, the purpose of this study was to characterize the exposure to NEOs, as well as OPs and PYRs, in three-year-old Japanese children by assessing the range, distribution, and seasonal differences of the urinary concentrations of seven NEOs (acetamiprid, clothianidin, dinotefuran, thiacloprid, thiamethoxam, imidacloprid, and nitenpyram); four OP metabolites (dialkylphosphates [DAPs]), including dimethylphosphate, dimethylthiophosphate, diethylphosphate, and diethylthiophosphate; and three PYR metabolites (3-phenoxybenzoic acid, trans-chrysanthemumdicarboxylic acid, and 3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid). Urine samples were collected from 223 children (108 males and 115 females) in the summer and winter months. The detection rates of NEOs were 58% for dinotefuran, 25% for thiamethoxam, 21% for nitenpyram, and <16% for all other NEOs. The median and maximum concentrations of the sum of the seven NEOs (ΣNEO) were 4.7 and 370.2nmol/g creatinine, respectively. Urinary ΣNEO, dimethylphosphate, and all PYR metabolite concentrations were significantly higher in the summer than in the winter (p<0.05). The creatinine-adjusted concentration of ΣNEO significantly correlated with those of all DAPs (p<0.05) but not with those of the PYR metabolites. Moreover, the NEO-detected group showed higher urinary ΣDAP (sum of four OP metabolites) concentrations than the group without NEO detection. These findings suggest that children in Japan are environmentally exposed to the three major insecticide lines, and that the daily exposure sources of NEOs

  18. QSAR analyses of organophosphates for insecticidal activity and its in-silico validation using molecular docking study.

    PubMed

    Niraj, Ravi Ranjan Kumar; Saini, Vandana; Kumar, Ajit

    2015-11-01

    The present work was carried out to design and develop novel QSAR models using 2D-QSAR and 3D-QSAR with CoMFA methodology for prediction of insecticidal activity of organophosphate (OP) molecules. The models were validated on an entirely different external dataset of in-house generated combinatorial library of OPs, by completely different computational approach of molecular docking against the target AChE protein of Musca domestica. The dock scores were observed to be in good correlation with 2D-QSAR and 3D-QSAR with CoMFA predicted activities and had the correlation coefficients (r(2)) of -0.62 and -0.63, respectively. The activities predicted by 2D-QSAR and 3D-QSAR with CoMFA were also observed to be highly correlated with r(2)=0.82. Also, the combinatorial library molecules were screened for toxicity in non-target organisms and degradability using USEPA-EPI Suite. The work was first step towards computer aided design and development of novel OP pesticide candidates with good insecticidal property but lower toxicity in non-targeted organisms and having biodegradation potential.

  19. Organophosphate agents induce plasma hypertriglyceridemia in mouse via single or dual inhibition of the endocannabinoid hydrolyzing enzyme(s).

    PubMed

    Suzuki, Himiko; Ito, Yuki; Noro, Yuki; Koketsu, Mamoru; Kamijima, Michihiro; Tomizawa, Motohiro

    2014-02-10

    Diverse serine hydrolases including endocannabinoid metabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have been suggested as secondary targets for organophosphate (OP) agents to exert adverse toxic effects such as lipid homeostasis disruption. The goal of this investigation is to verify that a major OP insecticide fenitrothion (FNT) induces plasma hypertriglyceridemia through the inhibition of FAAH and/or MAGL in comparison with that elicited by isopropyl dodecylfluorophosphonate (IDFP), a potent FAAH/MAGL inhibitor. Fasted mice were treated intraperitoneally with FNT or IDFP and were subsequently sacrificed for evaluations of plasma triglyceride (TG) levels and liver FAAH/MAGL activities. Plasma TG levels were significantly enhanced by the FNT or IDFP treatment (1.7- or 4.8-fold, respectively) compared with that of vehicle control. The IDFP exposure reduced the liver FAAH and MAGL activities, whereas the FNT exposure led to the preferential FAAH inhibition. The brain acetylcholinesterase was almost unaffected by the FNT or IDFP treatment, thus leading to no neurotoxic sign. Intriguingly, the TG elevations were averted by concomitant administration with the cannabinoid receptor antagonist AM251. The present findings suggest that OP agents induce plasma hypertriglyceridemia in mouse through single or dual inhibition of FAAH or/and MAGL, apparently leading to overstimulation of cannabinoid signal regulating energy metabolism.

  20. 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.

  1. 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.

  2. Probabilistic acute risk assessment of cumulative exposure to organophosphorus and carbamate pesticides from dietary vegetables and fruits in Shanghai populations.

    PubMed

    Li, Fan; Yuan, Yaqun; Meng, Pai; Wu, Min; Li, Shuguang; Chen, Bo

    2017-02-03

    Organophosphorus pesticides (OPs) and carbamate pesticides (CPs) are among the most widely used pesticides in China, playing a major role in protecting agricultural commodities. In this study, we determined the cumulative acute exposure to OPs and CPs of Shanghai residents from vegetables and fruits (VFs). The food consumption data were obtained from the Shanghai Food Consumption Survey (SHFCS) of 2012-14 including a total of 1973 participants aged 2-90 years. The pesticide residue data were obtained from the Shanghai monitoring programme during 2008-11 with 34 organophosphates and 11 carbamates analysed in a total of 5335 samples of VFs. A probabilistic approach was performed as recommended by the EFSA, using the optimistic model with non-detects set as zero and with processing factors (PFs) being used and the pessimistic model with non-detects replaced by limit of detection (LOD) and without PFs. We used the relative potency factor (RPF) method to normalise the various pesticides to the index compound (IC) of methamidophos and chlorpyrifos separately. Only in the pessimistic model using methamidophos as the IC was there was small risk of exposure exceeding the ARfD (3 µg kg(-)(1) bw day(-)(1)) in the populations of preschool children (0.029%), school-age children (0.022%) and adults (0.002%). There were no risk of exposure exceeding the ARfD of methamidophos in the optimistic model and of chlorpyrifos (100 µg kg(-)(1) bw day(-)(1)) in both optimistic and pessimistic models in all three populations. Considering the Chinese habits of overwhelmingly eating processed food (vegetables being cooked, and fruits being washed or peeled), we conclude that little acute risk was found for the exposure to VF-sourced OPs and CPs in Shanghai.

  3. Highly sensitive and selective amperometric microbial biosensor for direct determination of p-nitrophenyl-substituted organophosphate nerve agents.

    PubMed

    Lei, Yu; Mulchandani, Priti; Wang, Joseph; Chen, Wilfred; Mulchandani, Ashok

    2005-11-15

    We report herein a whole cell-based amperometric biosensor for highly selective, highly sensitive, direct, single-step, rapid, and cost-effective determination of organophosphate pesticides with a p-nitrophenyl substituent. The biosensor was comprised of a p-nitrophenol degrader, Pseudomonas putida JS444, genetically engineered to express organophosphorus hydrolase (OPH) on the cell surface immobilized on the carbon paste electrode. Surface-expressed OPH catalyzed hydrolysis of the p-nitrophenyl substituent organophosphorus pesticides such as paraoxon, parathion, and methyl parathion to release p-nitrophenol, which was subsequently degraded by the enzymatic machinery of P. putida JS444. The electrooxidization current of the intermediates was measured and correlated to the concentration of organophosphates. The best sensitivity and response time were obtained using a sensor constructed with 0.086 mg dry weight of cells operating at 600 mV applied potential (vs Ag/AgCl reference) in 50 mM citrate--phosphate pH 7.5 buffer with 50 microM CoCl2 at room temperature. Under optimum operating conditions the biosensor measured as low as 0.28 ppb of paraoxon, 0.26 ppb of methyl parathion, and 0.29 ppb parathion. These detection limits are comparable to cholinesterase inhibition-based biosensors. Unlike the inhibition-based format, this biosensor manifests a selective response to organophosphate pesticides with a p-nitrophenyl substituent only, has a simplified single-step protocol with short response time, and can be used for repetitive/multiple and on-line analysis. The service life of the microbial amperometric biosensor was 5 days when stored in the operating buffer at 4 degrees C. The new biosensor offers great promise for rapid environmental monitoring of OP pesticides with nitrophenyl substituent.

  4. Oxidative stress related to chlorpyrifos exposure in rainbow trout: Acute and medium term effects on genetic biomarkers.

    PubMed

    Benedetto, A; Brizio, P; Squadrone, S; Scanzio, T; Righetti, M; Gasco, L; Prearo, M; Abete, M C

    2016-05-01

    Organophosphates (OPs) are derivatives of phosphoric acid widely used in agriculture as pesticides. Chlorpyrifos (CPF) is an OP that is extremely toxic to aquatic organisms. Rainbow trout (Oncorhynchus mykiss) is considered as a sentinel model species for ecotoxicology assessment in freshwater ecosystems. An exposure study was carried out on rainbow trout to investigate genetic responses to CPF-induced oxidative stress by Real-Time PCR, and to determine the accumulation dynamics of CPF and toxic metabolite chlorpyrifos-oxon (CPF-ox) in edible parts, by HPLC-MS/MS. Among the genes considered to be related to oxidative stress, a significant increase in HSP70 mRNA levels was observed in liver samples up to 14 days after CPF exposure (0.05 mg/L). CPF concentrations in muscle samples reach mean values of 285.25 ng/g within 96 hours of exposure, while CPF-ox concentrations were always under the limit of quantification (LOQ) of the applied method. Our findings lead us to consider HSP70 as a suitable genetic marker in rainbow trout for acute and medium-term monitoring of CPF exposure, complementary to analytical determinations.

  5. Effect of paraoxonase 1 192 Q/R polymorphism on paraoxonase and acetylcholinesterase enzyme activities in a Turkish population exposed to organophosphate.

    PubMed

    Sunay, Seda Zengin; Kayaaltı, Zeliha; Bayrak, Tülin; Söylemezoğlu, Tülin

    2015-12-01

    Organophosphate (OP) compounds are the most commonly used pesticide groups and they are commercially used in the market for local and industrial purposes. Paraoxonase 1 (PON1) enzyme plays an important role in biotransformation of OP compounds, which shows toxic effects via inhibiting the acetylcholinesterase (AChE). The aim of this study was to determine the effects of PON1 gene polymorphism and its effects on PON and AChE enzyme activities in individuals who were exposed to organophosphorus insecticides due to occupational reasons, and to profile the probability of susceptibility to organophosphorus compounds. For this purpose, 54 individuals who were exposed to OPs and 54 healthy unrelated controls were studied. First, PON1 and AChE enzyme activities were measured. Second, PON1 192 Q/R polymorphism was determined by standard polymerase chain reaction-restriction fragment length polymorphism technique. When the PON1 192 Q/R polymorphism was compared with PON1 enzyme activities, statistically significant association was found in both OP-exposed and control groups (p < 0.05). PON1 192 R(+) (QR + RR genotypes) genotype carriers had higher PON1 activities than 192 R(-) (QQ) genotype carriers. On the other hand, results were statistically analyzed in terms of AChE enzyme activities and there were statistically significant differences only in the OP-exposed group (p < 0.05). The mean AChE concentration in the OP-exposed group was determined as 33.79 ± 6.84 U/g haemoglobin (Hb) for PON1 192 R(+) carriers and 30.37 ± 7.62 U/g Hb for PON1 192 R(+) carriers. As a conclusion, PON1 and AChE activities were increasing according to the genotypes found in individuals having been exposed to OPs at a chronic level; 192 R(+) > 192 R(-), respectively.

  6. Comparative Kinetics and Distribution to Target Tissues of Organophosphates Using Physiologically - Based Pharmacokinetic Modeling

    DTIC Science & Technology

    2008-03-01

    COMPARATIVE KINETICS AND DISTRIBUTION TO TARGET TISSUES OF ORGANOPHOSPHATES USING PHYSIOLOGICALLY...Department of Defense, or the U.S. Government. AFIT/GEM/ENV/08-M20 COMPARATIVE KINETICS AND DISTRIBUTION TO TARGET TISSUES OF ORGANOPHOSPHATES...APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED AFIT/GEM/ENV/08-M20 COMPARATIVE KINETICS AND DISTRIBUTION TO TARGET TISSUES OF ORGANOPHOSPHATES

  7. Associations of Prenatal Exposure to Organophosphate Pesticide Metabolites with Gestational Age and Birth Weight

    PubMed Central

    Rauch, Stephen A.; Braun, Joe M.; Barr, Dana Boyd; Calafat, Antonia M.; Khoury, Jane; Montesano, M. Angela; Yolton, Kimberly

    2012-01-01

    Background: Prenatal exposure to organophosphate (OP) insecticides, a widely used class of pesticides, may be associated with decreased gestational age and lower birth weight. Single nucleotide polymorphisms in paroxanase (PON1) enzyme genotypes may modify the relationships between OP exposure and perinatal outcomes. Objective: We examined the relationship of prenatal OP insecticide exposure, measured using urinary dialkyl phosphate (DAP) metabolite concentrations, with gestational age and birth weight. Methods: We measured the concentrations of six nonspecific DAP metabolites of OP insecticides in two maternal spot urine samples collected in a prospective birth cohort. We performed multivariable regression to examine associations between the sum of six DAP concentrations (ΣDAP) with gestational age and birth weight. We also examined whether these associations differed according to infant PON1192 and PON1–108 genotypes. Results: Among 306 mother–infant dyads, a 10-fold increase in ΣDAP concentrations was associated with a decrease in covariate-adjusted gestational age [–0.5 weeks; 95% confidence interval (CI): –0.8, –0.1] and birth weight (–151 g; CI: –287, –16); the decrements in birth weight were attenuated after adjusting for gestational age. The relationship between ΣDAP concentrations and gestational age was stronger for white (–0.7 weeks; CI: –1.1, –0.3) than for black (–0.1 weeks; 95% CI: –0.9, 0.6) newborns. In contrast, there was a greater decrease in birth weight with increasing urinary ΣDAP concentrations for black (–188 g; CI: –395, 19) than for white (–118 g; CI: –296, 60) newborns. Decrements in birth weight and gestational age associated with ΣDAP concentrations were greatest among infants with PON1192QR and PON–108CT genotypes. Conclusions: Prenatal urinary ΣDAP concentrations were associated with shortened gestation and reduced birth weight in this cohort, but the effects differed by race/ethnicity and PON

  8. Modulation of dopaminergic neurotransmission induced by sublethal doses of the organophosphate trichlorfon in cockroaches.

    PubMed

    Stürmer, Graziele Daiane; de Freitas, Thiago Carrazoni; Heberle, Marines de Avila; de Assis, Dênis Reis; Vinadé, Lúcia; Pereira, Antônio Batista; Franco, Jeferson Luis; Dal Belo, Cháriston André

    2014-11-01

    Organophosphate (OP) insecticides have been used indiscriminately, based on their high dissipation rates and low residual levels in the environment. Despite the toxicity of OPs to beneficial insects is principally devoted to the acetylcholinesterase (AChE) inhibition, the physiological mechanisms underlying this activity remain poorly understood. Here we showed the pharmacological pathways that might be involved in severe alterations in the insect locomotion and grooming behaviors following sublethal administration of the OP Trichlorfon (Tn) (0.25, 0.5 and 1 µM) in Phoetalia pallida. Tn inhibited the acetylcholinesterase activity (46±6, 38±3 and 24±6 nmol NADPH/min/mg protein, n=3, p<0.05), respectively. Tn (1 µM) also increased the walking maintenance of animals (46±5 s; n=27; p<0.05). Tn caused a high increase in the time spent for this behavior (344±18 s/30 min, 388±18 s/30 min and 228±12 s/30 min, n=29-30, p<0.05, respectively). The previous treatment of the animals with different cholinergic modulators showed that pirenzepine>atropine>oxotremorine>d-tubocurarine>tropicamide>methoctramine induced a decrease on Tn (0.5 µM)-induced grooming increase, respectively in order of potency. Metoclopramide (0.4 µM), a DA-D2 selective inhibitor decreased the Tn-induced grooming activity (158±12 s/30 min; n=29; p<0.05). Nevertheless, the effect of the selective DA-D1 receptor blocker SCH 23390 (1.85 µM) on the Tn (0.5 µM)-induced grooming increase was significative and more intense than that of metoclopramide (54±6 s/30 min; n=30; p<0.05). Taken together the results suggest that a cross-talking between cholinergic M1/M3 and dopaminergic D1 receptors at the insect nervous system may play a role in the OP-mediated behavioral alterations.

  9. OPS83: Style Guide for High Performance.

    DTIC Science & Technology

    1987-06-01

    er and ,de,,l U by Sc Mor,o’ - FIEL GRUP SB-GOUP Artificial intelligence, rule-based systems, OPS83, Rete algorithm, program optimization 19 ABTAC Coot...OPS83....................................................... I Rete Match Algorithm ....................................................... Function ...implementation of the Rete algorithm reported here. RETE MATCH ALGORITHM Function /Overview The function of the Rete match algorithm is to compute the

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

    PubMed

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

    2016-07-01

    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 1.6-10ngmL(-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 0.09-2.66ngmL(-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 in those

  11. Reprint of 'Evaluating organophosphate poisoning in human serum with paper'.

    PubMed

    Yen, Tzung-Hai; Chen, Kuan-Hung; Hsu, Min-Yen; Fan, Shu-Ting; Huang, Yu-Fen; Chang, Chia-Ling; Wang, Yu-Ping; Cheng, Chao-Min

    2015-12-01

    This manuscript describes the development and clinical testing of a paper-based, metabolic assay designed for rapid, semi-quantitative measurement of organophosphate poisoning. Paper-based platforms, including point-of-care devices and 96-well plates, provided semi-quantitative information regarding the concentration of AchE (a biomarker for organophosphate poisoning). The paper-based 96-well-plate developed and implemented in this study was used to measure the level of organophosphate poisoning in three different clinical patients. Results were comparable to those obtained using conventional hospital methods currently considered the "gold standard". This diagnostic device offers several advantages over conventional methods, including short operating time (twice as fast as conventional methods), procedure simplicity, and reduced fabrication cost. With further commercialization efforts, the methods described in this manuscript could be applied to a wide range of potential diagnostic applications in the field.

  12. Evaluating organophosphate poisoning in human serum with paper.

    PubMed

    Yen, Tzung-Hai; Chen, Kuan-Hung; Hsu, Min-Yen; Fan, Shu-Ting; Huang, Yu-Fen; Chang, Chia-Ling; Wang, Yu-Ping; Cheng, Chao-Min

    2015-11-01

    This manuscript describes the development and clinical testing of a paper-based, metabolic assay designed for rapid, semi-quantitative measurement of organophosphate poisoning. Paper-based platforms, including point-of-care devices and 96-well plates, provided semi-quantitative information regarding the concentration of AchE (a biomarker for organophosphate poisoning). The paper-based 96-well-plate developed and implemented in this study was used to measure the level of organophosphate poisoning in three different clinical patients. Results were comparable to those obtained using conventional hospital methods currently considered the "gold standard". This diagnostic device offers several advantages over conventional methods, including short operating time (twice as fast as conventional methods), procedure simplicity, and reduced fabrication cost. With further commercialization efforts, the methods described in this manuscript could be applied to a wide range of potential diagnostic applications in the field.

  13. 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

  14. 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.

  15. Histopathological alterations, biochemical responses and acetylcholinesterase levels in Clarias gariepinus as biomarkers of exposure to organophosphates pesticides.

    PubMed

    Doherty, V F; Ladipo, M K; Aneyo, I A; Adeola, A; Odulele, W Y

    2016-05-01

    Organophosphate pesticides, commonly used in large scale farming, have been found to be major contaminants in aquatic environment. Clarias gariepinus was exposed to acute and sublethal concentrations of phostoxin and DD Force to evaluate single and joint action toxicity of the organophosphates. Effects of phostoxin and DD force on antioxidant enzymes, fish organs and acetylcholinesterase levels in fingerlings and juveniles of C. gariepinus were also investigated. The lethal concentrations (96 h LC50) for phostoxin and DD Force were 0.631 and 1.759 mg/l, respectively. The results obtained from the bioassay showed that phostoxin was 2.8× more toxic than DD Force after exposure of C. gariepinus. Joint action toxicity evaluations of phostoxin and DD Force showed that the interaction between the chemicals was synergistic (RTU >1). The biochemical responses in the exposed fish differed significantly (P < 0.05) from the control fish. The result of acetylcholinesterase study revealed significant difference between acetylcholinesterase levels in the exposed fish and control, with reduction in the acetylcholineterase level in fish exposed to sublethal concentrations of phostoxin and DD Force. Haematological studies revealed an increase in WBC, RBC, PCV and platelets in the exposed fish. Histopathology of the gills showed shortened primary lamellae, loss of secondary lamellae and loss of ceratobrachial bones. In the acute toxicity studies, respiratory stress, erratic swimming and instant death of fish were observed in the exposed fish. This study reveals that changes in histopathology and acetylcholinesterase level are good biomarkers and can be successfully used to detect exposure to organophosphates pesticides in fish.

  16. Performance assessment of the SOFA, APACHE II scoring system, and SAPS II in intensive care unit organophosphate poisoned patients.

    PubMed

    Kim, Yong Hwan; Yeo, Jung Hoon; Kang, Mun Ju; Lee, Jun Ho; Cho, Kwang Won; Hwang, SeongYoun; Hong, Chong Kun; Lee, Young Hwan; Kim, Yang Weon

    2013-12-01

    This study assessed the ability of the Sequential Organ Failure Assessment (SOFA) and Acute Physiology, Chronic Health Evaluation (APACHE) II scoring systems, as well as the Simplified Acute Physiology Score (SAPS) II method to predict group mortality in intensive care unit (ICU) patients who were poisoned with organophosphate. The medical records of 149 organophosphate poisoned patients admitted to the ICU from September 2006 to December 2012 were retrospectively examined. The SOFA, APACHE II, and SAPS II were calculated based on initial laboratory data in the Emergency Department, and during the first 24 hr of ICU admission. The probability of death was calculated for each patient based on the SOFA score, APACHE II score, and SAPS II equations. The ability to predict group mortality by the SOFA score, APACHE II score, and SAPS II method was assessed using two by two decision matrices and receiver operating characteristic (ROC) curve analysis. A total of 131 patients (mean age, 61 yr) were enrolled. The sensitivities, specificities, and accuracies were 86.2%, 82.4%, and 83.2% for the SOFA score, respectively; 65.5%, 68.6%, and 67.9% for the APACHE II scoring system, respectively; and 86.2%, 77.5%, and 79.4% for the SAPS II, respectively. The areas under the curve in the ROC curve analysis for the SOFA score, APACHE II scoring system, and SAPS II were 0.896, 0.716, and 0.852, respectively. In conclusion, the SOFA, APACHE II, and SAPS II have different capability to discriminate and estimate early in-hospital mortality of organophosphate poisoned patients. The SOFA score is more useful in predicting mortality, and easier and simpler than the APACHE II and SAPS II.

  17. 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), ...

  18. Selective Binding of Organophosphate Pesticides Using Molecular Imprinted Polymers

    DTIC Science & Technology

    2005-10-01

    MIPs . SELECTIVE BINDING OF ORGANOPHOSPHATE PESTICIDES USING MOLECULAR IMPRINTED POLYMERS . *Ali M. Saboori...Maryland 20910-7500. ABSTRACT Molecular Imprinted Polymers ( MIPs ) have been used for recognition and binding of different compounds. We are...INTRODUCTION Molecular Imprinted Polymers ( MIPs ) are highly cross-linked polymers , which are formed by cross- linking monomer in

  19. Biosensor based on acetylcholinesterase immobilized onto layered double hydroxides for flow injection/amperometric detection of organophosphate pesticides.

    PubMed

    Gong, Jingming; Guan, Zhangqiong; Song, Dandan

    2013-01-15

    We developed a highly sensitive flow injection/amperometric biosensor for the detection of organophosphate pesticides (OPs) using layered double hydroxides (LDHs) as the immobilization matrix of acetylcholinesterase (AChE). LDHs provided a biocompatible microenvironment to keep the bioactivity of AChE, due to the intrinsic properties of LDHs (such as a regular structure, good mechanical, chemical and thermal stabilities, and swelling properties). By integrating the flow injection analysis (FIA) with amperometric detection, the resulting AChE-LDHs modified electrode greatly catalyzed the oxidation of the enzymatically generated thiocholine product, and facilitated the detection automation, thus increasing the detection sensitivity. The analytical conditions for the FIA/amperometric detection of OPs were optimized by using methyl parathion (MP) as a model. The inhibition of MP was proportional to its concentration ranging from 0.005 to 0.3μg mL(-1) and 0.3 to 4.0μg mL(-1) with a detection limit 0.6ng mL(-1) (S/N=3). The developed biosensor exhibited good reproducibility and acceptable stability.

  20. Identification of a major Quantitative Trait Locus determining resistance to the organophosphate temephos in the dengue vector mosquito Aedes aegypti.

    PubMed

    Paiva, Marcelo H S; Lovin, Diane D; Mori, Akio; Melo-Santos, Maria A V; Severson, David W; Ayres, Constância F J

    2016-01-01

    Organophosphate insecticides (OP) have extensively been used to control mosquitoes, such as the vector Aedes aegypti. Unfortunately, OP resistance has hampered control programs worldwide. We used Quantitative Trait Locus (QTL) mapping to evaluate temephos resistance in two F1 intercross populations derived from crosses between a resistant Ae. aegypti strain (RecR) and two susceptible strains (MoyoD and Red). A single major effect QTL was identified on chromosome 2 of both segregating populations, named rtt1 (resistance to temephos 1). Bioinformatics analyses identified a cluster of carboxylesterase genes (CCE) within the rtt1 interval. qRT-PCR demonstrated that different CCEs were up-regulated in F2 resistant individuals from both crosses. However, none exceeded the 2-fold expression. Primary mechanisms for temephos resistance may vary between Ae. aegypti populations, yet also appear to support previous findings suggesting that multiple linked esterase genes may contribute to temephos resistance in the RecR strain as well as other populations.

  1. THE EFFECTS OF AN ORGANOPHOSPHATE (OP)-CARBAMATE (CB) PESTICIDE MIXTURE ON CORE TEMPERATURE AND MOTOR ACTIVITY IN THE RAT.

    EPA Science Inventory

    Pesticide risk assessment has traditionally been based on the toxicological response to single agents. Dose-additivity has been the default in risk assessment evaluations of pesticides with a common mechanism of action, but there could be supra-additive or infra-additive inter...

  2. The CO-OP Guide

    SciTech Connect

    Michael, J.; /Fermilab

    1991-08-16

    You are at D0, the newest and most advanced experiment at Fermilab. Its goal is to find the 'top quark', nicknamed 'truth'. theoretically one of the six fundamental building blocks of matter. Combinations of the six quarks are said to make up electrons, protons and neutrons. Your group at D0 is the cryogenic division. Its goal is to provide and maintain a cryogenic system which ultimately supplies and controls the liquid argon used in the giant cryostats for the experiment. The high purity liquid argon is needed to keep the detector modules inside the cryostats cold, so that they will operate properly. Your job at D0 is to be a co-op for the research and development group of the cryogenics division. Your goals are dependent on the needs of the cryo group. D0 is where you will spend most of your time. The co-op office is located on what is known as the 3rd floor, but is actually on the ground floor. The floor directly above the 3rd floor is the 5th floor, which contains your immediate superiors and the D0 secretary. The 6th and top floor is above that, and contains the D0 secretary for official and important business. On the other side of the D0 assembly building is the cryo control room. This is where the cryogenic piping system is remotely monitored and controlled. Other important sites at D0 include the trailer city on the north parking lot, which has the D0 secretary who handles all the payroll matters (among other duties), and the portakamp in the south parking lot. Besides D0, which is named for its location on the particle accelerator ring. the most important place is Wilson Hall. That is the large building shaped like a big Atact symbol. It contains various important people such as the safety group. the personnel department (which you have already encountered. being hired), the minor stock room, the cafeteria, the Fermi library. Ramsey Auditorium. etc. Behind Wilson Hall is the Booster Ring, which accelerates particles before they are injected into the main

  3. 45 CFR 156.515 - CO-OP standards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false CO-OP standards. 156.515 Section 156.515 Public... Operated and Oriented Plan Program § 156.515 CO-OP standards. (a) General. A CO-OP must satisfy the...) Governance requirements. A CO-OP must meet the following governance requirements: (1) Member control. A...

  4. 45 CFR 156.515 - CO-OP standards.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false CO-OP standards. 156.515 Section 156.515 Public... Operated and Oriented Plan Program § 156.515 CO-OP standards. (a) General. A CO-OP must satisfy the...) Governance requirements. A CO-OP must meet the following governance requirements: (1) Member control. A...

  5. 45 CFR 156.515 - CO-OP standards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false CO-OP standards. 156.515 Section 156.515 Public... Operated and Oriented Plan Program § 156.515 CO-OP standards. (a) General. A CO-OP must satisfy the...) Governance requirements. A CO-OP must meet the following governance requirements: (1) Member control. A...

  6. Organophosphate Insecticide Metabolites in Prenatal and Childhood Urine Samples and Intelligence Scores at 6 Years of Age: Results from the Mother–Child PELAGIE Cohort (France)

    PubMed Central

    Cartier, Chloé; Warembourg, Charline; Le Maner-Idrissi, Gaïd; Lacroix, Agnès; Rouget, Florence; Monfort, Christine; Limon, Gwendolina; Durand, Gaël; Saint-Amour, Dave; Cordier, Sylvaine; Chevrier, Cécile

    2015-01-01

    Background: Several studies suggest that exposure to organophosphate insecticides (OP) during pregnancy impairs neurodevelopment in children. Objectives: We evaluated associations between biomarkers of prenatal and postnatal OP exposure and cognitive function of 6-year-olds in a French longitudinal birth cohort. Methods: In 2002–2006, the PELAGIE mother–child cohort enrolled pregnant women from Brittany. For a random subcohort, we measured nonspecific dialkylphosphate metabolites (DAP) of OP in one maternal urine sample, collected before 19 weeks’ gestation, and in one urine sample collected from their 6-year-old children. Six subtests of the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) were administered when the children were 6 years of age to evaluate cognitive function (n = 231). Linear regression models controlling for factors including maternal intelligence and the Home Observation for Measurement of the Environment score were used. Results: WISC-IV scores were not significantly associated with prenatal or childhood total DAP metabolites. WISC verbal comprehension score was significantly higher in association with the highest maternal urinary concentrations of diethylphosphate (DE) metabolites (5.5; 95% CI: 0.8, 10.3 for > 13.2 nmol/L vs. < LOQ), whereas WISC working memory score was significantly lower in association with the highest urinary concentrations of DE metabolites at age 6 years (–3.6; 95% CI: –7.8, –0.6 for > 11.1 nmol/L vs. < LOD). Conclusion: We found no evidence that prenatal OP exposure adversely affected cognitive function in 6-year-olds, perhaps because of the population’s socioeconomic status, which was higher than in previous studies, though other causal and noncausal explanations are also possible. The negative association between WISC score and concurrent DE urinary concentrations requires replication by longitudinal studies investigating childhood OP exposure. Citation: Cartier C, Warembourg C, Le Maner

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

    SciTech Connect

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

    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, 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 those

  8. Metabonomic analysis of the joint toxic action of long-term low-level exposure to a mixture of four organophosphate pesticides in rat plasma.

    PubMed

    Du, Longfei; Li, Sifan; Qi, Lei; Hou, Yurong; Zeng, Yan; Xu, Wei; Wang, Hong; Zhao, Xiujuan; Sun, Changhao

    2014-05-01

    In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) in rats using metabonomic technology at their corresponding no observed adverse effect levels (NOAELs). The results show that a single pesticide did not elicit a toxic response. The joint toxic action of four pesticides (at their corresponding NOAELs) was evaluated by metabolomic analysis of rat plasma under experimental conditions similar to those of the four single OP pesticides. The pesticides were administered daily to rats through drinking water for 24 weeks. The mixture of four pesticides showed a joint toxic action at the NOAELs of each pesticide. The 19 metabolites were statistically significantly changed in all the treated groups compared with those in the control group (p < 0.05 or p < 0.01). Exposure to OP pesticides resulted in increased lysoPC (15 : 0/0 : 0), lysoPC (16 : 0/0 : 0), lysoPC (O-18 : 0/0 : 0), lysoPC (P-19 : 1(12Z)/0 : 0), lysoPC (18 : 1(9Z)/0 : 0), lysoPC (18 : 0/0 : 0), lysoPC (20 : 4(5Z, 8Z, 11Z, 14Z)/0 : 0), lysoPE (16 : 0/0 : 0), lysoPC (17 : 0/0 : 0), 4-pyridoxic acid, glutamic acid, glycocholic acid, and arachidonic acid, as well as decreased C16 sphinganine, C17 sphinganine, phytosphingosine, indoleacrylic acid, tryptophan, and iodotyrosine in rat plasma. The results indicate that the mixture of OP pesticides induced oxidative stress, liver and renal dysfunction, disturbed the metabolism of lipids and amino acids, and interfered with the function of the thyroid gland. The present plasma results provided complementarities with our previous metabolomic analysis of the rat urine profile exposed to a mixture of four OP pesticides, and also contributed to the understanding of the mechanism of joint toxic action.

  9. 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

  10. Repeated low-dose organophosphate DFP exposure leads to the development of depression and cognitive impairment in a rat model of Gulf War Illness.

    PubMed

    Phillips, Kristin F; Deshpande, Laxmikant S

    2016-01-01

    Approximately 175,000-250,000 of the returning veterans from the 1991 Persian Gulf War exhibit chronic multi-symptom illnesses that includes neurologic co-morbidities such as depression, anxiety and cognitive impairments. Amongst a host of causative factors, exposure to low levels of the nerve agent Sarin has been strongly implicated for expression of Gulf War Illness (GWI). Nerve agents similar to pesticides are organophosphate (OP) compounds. There is evidence from civilian population that exposure to OPs such as in agricultural workers and nerve agents such as the survivors and first-responders of the Tokyo subway Sarin gas attack suffer from chronic neurological problems similar to GWI symptoms. Given this unique chemical profile, OPs are ideal to study the effects of nerve agents and develop models of GWI in civilian laboratories. In this study, we used repeated low-dose exposure to OP agent diisopropyl fluorophosphate (DFP) over a 5-day period to approximate the duration and level of Sarin exposure during the Persian Gulf War. We tested the rats at 3-months post DFP exposure. Using a battery of behavioral assays, we observed the presence of symptoms of chronic depression, anxiety and memory problems as characterized by increased immobility time in the Forced Swim Test, anhedonia in the Sucrose Preference Test, anxiety in the Elevated Plus Maze, and spatial memory impairments in the Object Location Test, respectively. Chronic low dose DFP exposure was also associated with hippocampal neuronal damage as characterized by the presence of Fluoro-Jade staining. Given that OP exposure is considered a leading cause of GWI related morbidities, this animal model will be ideally suited to study underlying molecular mechanisms for the expression of GWI neurological symptoms and identify drugs for the effective treatment of GWIs.

  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. OpTIIX Mission Overview and Education/Public Outreach

    NASA Astrophysics Data System (ADS)

    Krueger, T.; Swade, D.

    2013-10-01

    The Optical Testbed and Integration on ISS Experiment (OpTIIX) is a technology demonstration to design, develop, deliver, robotically assemble, and successfully operate an observatory on the International Space Station (ISS). An OpTIIX Education and Public Outreach (EPO) program is being designed to bring OpTIIX and its discoveries to amateur observers, students, educators, and the public. In addition OpTIIX will be available to the professional community for additional tests using the assembled OpTIIX configuration.

  13. 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.

  14. 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.

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

    PubMed Central

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

    2014-01-01

    Organophosphate (OP) compounds are used as insecticides, acaracides, 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 μM to 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. PMID:24486155

  16. A preliminary investigation of insect colonization and succession on remains of rabbits treated with an organophosphate insecticide in El-Qalyubiya Governorate of Egypt.

    PubMed

    Abd El-bar, M M; Sawaby, R F

    2011-05-20

    A preliminary field study in the summer in a rural village in El-Qalyubiya Governorate (Egypt) compared the necrophagous insects colonizing the cadavers of two male rabbits (Oryctolagus cunicullus domesticus L.) killed by asphyxia (control), with two poisoned by the organophosphate (OP) pesticide pirimiphos-methyl (test). Decay of control carcasses was rapid since they reached the skeletal stage in only 19 days. Test carcasses did not decay completely, even 40 days post-killing. Insect species colonizing both carcasses types were not different, indicating that despite its odor, the OP were not masking the decomposition odors which were drawing the species to the bodies. The blowfly Chrysomya albiceps (Weidemann) constituted 76.6% of all samples collected. They were the first colonizers and played a major role in the decomposition process of control carcasses and in the partial decay of the test ones. They were significantly fewer numbers of immature stages developing on the test carcasses which probably contributed to their distinct lag and poor decomposition. Samples indicate that 17.3% of the insects were members of the Formicidae. This family was present in all carcasses, mostly in the early stages of decomposition. Formicidae may be considered omnivorous, and one of the fauna which use the cadaver as a refuge, to obtain humidity and food. This study provides additional knowledge in the context of Egyptian forensic entomology and the influence of OP which is of relevance to forensic science.

  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. [Pretreatment of organophosphate poisoning: potential interests of huperzine A].

    PubMed

    Lallement, G

    2000-01-01

    Pyridostigmine which is widely used as pretreatment of organophosphate poisoning protects cholinesterases of peripheral nervous system. Other molecules able to also protect the central nervous system are under study and, among them, huperzine A. This paper gives an overview of the current investigations about the efficacy and the innocuity of this molecule (study of the mechanisms of action, biological targets, behavioural manifestations) and brings out its potential interests.

  19. Hyperspectral Imagery for Large Area Survey of Organophosphate Pesticides

    DTIC Science & Technology

    2015-03-26

    assumptions made in the course of this research. Some of these were due to the nature of conducting experiments in the lab. Others arose from the...chemicals present. The more volatile nature of these additives may lessen this effect, but was not explored in the course of this research...presented. Relevant Research Organophosphates are esters of phosphoric acid that are widely used as herbicides, insecticides and chemical warfare

  20. Design, Synthesis and Study of Catalysts for Organophosphate Ester Hydrolysis.

    DTIC Science & Technology

    1985-07-01

    catalysts for phosphate ester hydrolyses which are modelled after carbonic anhydrase (CA) and alkaline phosphatase (APase). Section II describes the...Catalysts for Hydrolysis of Phosphate Esters. Alkaline phosphatases (APases) are Zn(II)- and Mg(II)- containing metalloenzymes found in virtually every...E TA "APR 14 07 k-1 le -p /m mm Alkaline phosphatase , models, catalysis, organophosphate ester, hydrolysis, metal ion 2"n.VUAC? - ",N-060 p MV ad& N

  1. Piezoelectric Biosensors for Organophosphate and Carbamate Pesticides: A Review

    PubMed Central

    Marrazza, Giovanna

    2014-01-01

    Due to the great amount of pesticides currently being used, there is an increased interest for developing biosensors for their detection. Among all the physical transducers, piezoelectric systems have emerged as the most attractive due to their simplicity, low instrumentation costs, possibility for real-time and label-free detection and generally high sensitivity. This paper presents an overview of biosensors based on the quartz crystal microbalance, which have been reported in the literature for organophosphate and carbamate pesticide analysis. PMID:25587424

  2. 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

  3. Monitoring acute and chronic water column toxicity in the Northern Sacramento-San Joaquin Estuary, California, USA, using the euryhaline amphipod, Hyalella azteca: 2006 to 2007.

    PubMed

    Werner, Inge; Deanovic, Linda A; Markiewicz, Dan; Khamphanh, Manisay; Reece, Charles K; Stillway, Marie; Reece, Charissa

    2010-10-01

    After the significant population decline of several pelagic fish species in the Northern Sacramento-San Joaquin (SSJ) Estuary (CA, USA) in 2002, a study was performed to monitor water column toxicity using the amphipod Hyalella azteca. From January 1, 2006 to December 31, 2007, water samples were collected biweekly from 15 to 16 sites located in large delta channels and main-stem rivers, selected based on prevalent distribution patterns of fish species of concern. Ten-day laboratory tests with H. azteca survival and relative growth as toxicity endpoints were conducted. The enzyme inhibitor piperonyl butoxide ([PBO], 25 µg/L) was added to synergize or antagonize pyrethroid or organophosphate (OP) insecticide toxicity, respectively. Significant amphipod mortality was observed in 5.6% of ambient samples. Addition of PBO significantly changed survival or growth in 1.1% and 10.1% of ambient samples, respectively. Sites in the Lower Sacramento River had the largest number of acutely toxic samples, high occurrence of PBO effects on amphipod growth (along with sites in the South Delta), and the highest total ammonia/ammonium concentrations (0.28 ± 0.15 mg/L). Ammonia/ammonium, or contaminants occurring in mixture with these, likely contributed to the observed toxicity. Pyrethroid insecticides were detected at potentially toxic concentrations. Overall, results of this study identified specific areas and contaminants of concern and showed that water in the Northern SSJ Estuary was at times acutely toxic to sensitive invertebrates.

  4. 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

  5. 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.

  6. In Vitro Rat Hepatic and Intestinal Metabolism of the Organophosphate Pesticides Chlorpyrifos and Diazinon

    SciTech Connect

    Poet, Torka S. ); Wu, Hong ); Kousba, Ahmed A. ); Timchalk, Charles

    2003-04-01

    Chlorpyrifos (CPF) and diazinon (DZN) are thionophosphorus organophosphate, insecticides; their toxicity is mediated through CYP450 metabolism to CPF-oxon and DZN-oxon, respectively. Conversely, CYP450s also detoxify these OPs to trichloropyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP), respectively. In addition, A-esterase metabolism of CPF- and DZN-oxon also form TCP and IMHP. This study evaluated the role intestinal and hepatic metabolism may play in the first-pass elimination of CPF and DZN. Similar CYP450- and A-esterase-mediated metabolic profiles were demonstrated in microsomes from liver or isolated intestinal enterocytes. In enterocyte microsomes, the CYP450 metabolic efficiency (Vmax/Km) for metabolism to the oxon metabolites was~5-fold greater for CPF than DZN. Compared on a per nmol P450 basis, the Vmax for CPF in enterocytes was~2-3 times higher than in liver microsomes for the production of CPF-oxon and TCP. The affinity (Km) for the metabolism of CPF to CPF-oxon was comparable in liver and enterocyte microsomes, however the enterocyte Km for TCP production was higher (lower affinity). The smaller volume of intestine, lower amount of CYP450, and higher Km for TCP in the enterocyte microsomes, resulted in a lower catalytic efficiency (2 and 62 times) than in liver for oxon and TCP. A-esterase-mediated metabolism of CPF- and DZN-oxon was also demonstrated in liver and enterocyte microsomes. Although A-esterase affinity for the substrates were comparable in hepatic and enterocyte microsomes, the Vmax were 48 - to 275-fold, in the liver. These results suggest that intestinal metabolism may impact first-pass metabolism of CPF and DZN, especially following low-dose oral exposures.

  7. Usefulness of administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using paraoxon.

    PubMed

    Petroianu, Georg A; Nurulain, Syed M; Shafiullah, Mohamed; Hasan, Mohamed Y; Kuča, Kamil; Lorke, Dietrich E

    2013-09-01

    Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality-reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death. Best in vivo protection from paraoxon-induced mortality was observed after prophylactic administration of physostigmine (RR = 0.30) or the oxime K-27 (RR = 0.34); both treatments were significantly superior to the pre-treatment with all other tested compounds, including the established substance pyridostigmine. Tacrine (RR = 0.67), ranitidine (RR = 0.72), pyridostigmine (RR = 0.76), tiapride (RR = 0.80) and 7-MEOTA (RR = 0.86) also significantly reduced the relative risk of paraoxon-induced death, but to a lesser degree. Methylene blue, amiloride and metoclopramide had an unfavorable effect (RR ≥ 1), significantly increasing mortality. When CNS penetration by prophylactic is undesirable K-27 is a promising alternative to pyridostigmine.

  8. Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone.

    PubMed

    Lorke, Dietrich E; Nurulain, Syed M; Hasan, Mohamed Y; Kuča, Kamil; Petroianu, Georg A

    2014-10-01

    Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC-induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)-approved substance for such pre-treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad-spectrum alternatives, we have assessed in vivo the mortality-reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01 ) 30 min before exposure to the OPC terbufos sulfone. Protection was quantified in rats by determining the relative risk of death (RR) using Cox analysis, with RR = 1 for animals given only terbufos sulfone, but no pre-treatment. All tested AChE inhibitors reduced terbufos sulfone-induced mortality significantly (p ≤ 0.05) as compared with the non-treatment group (RR = 1: terbufos sulfone only). Best in vivo protection from terbufos sulfone-induced mortality was achieved, when K-27 was given before terbufos sulfone exposure (RR = 0.06), which was significantly (P ≤ 0.05) superior to the pre-treatment with all other tested compounds, for example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR = 0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine, pyridostigmine, physostigmine and ranitidine were not statistically significant. Prophylactic administration of an oxime (such as K-27) in case of imminent OPC exposure may be a viable option.

  9. Organophosphate Pesticide Exposure and Attention in Young Mexican-American Children: The CHAMACOS Study

    PubMed Central

    Marks, Amy R.; Harley, Kim; Bradman, Asa; Kogut, Katherine; Barr, Dana Boyd; Johnson, Caroline; Calderon, Norma; Eskenazi, Brenda

    2010-01-01

    Background Exposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children. Objectives We investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California. Methods Children were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale. Results Prenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: β = 0.7 points; 95% confidence interval (CI), 0.2–1.2; ADHD: β = 1.3; 95% CI, 0.4–2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7–15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1–10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention. Conclusions In utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys. PMID:21126939

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

    PubMed

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

    2015-05-01

    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 during both seasons. 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

  11. Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse.

    PubMed

    Wiktor-Jedrzejczak, W; Bartocci, A; Ferrante, A W; Ahmed-Ansari, A; Sell, K W; Pollard, J W; Stanley, E R

    1990-06-01

    Osteopetrotic (op/op) mutant mice suffer from congenital osteopetrosis due to a severe deficiency of osteoclasts. Furthermore, the total number of mononuclear phagocytes is extremely low in affected mice. Serum, 11 tissues, and different cell and organ conditioned media from op/op mice were shown to be devoid of biologically active colony-stimulating factor 1 (CSF-1), whereas all of these preparations from littermate control +/+ and +/op mice contained the growth factor. The deficiency was specific for CSF-1 in that serum or conditioned media from op/op mice possessed elevated levels of at least three other macrophage growth factors. Partial correction of the op/op defect was observed following intraperitoneal implantation of diffusion chambers containing L929 cells, which in culture produce CSF-1 as their sole macrophage growth factor. No rearrangement of the CSF-1 gene in op/op mice was detected by Southern analysis. However, in contrast to control lung fibroblasts, which contained 4.6- and 2.3-kilobase CSF-1 mRNAs, only the 4.6-kilobase species was detected in op/op cells. An alteration in the CSF-1 gene is strongly implicated as the primary defect in op/op mice because they do not contain detectable CSF-1, their defect is correctable by administration of CSF-1, the op locus and the CSF-1 gene map within the same region of mouse chromosome 3, their CSF-1 mRNA biosynthesis is altered, and the op/op phenotype is consistent with the phenotype expected in a CSF-1 deficient mouse.

  12. 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

  13. 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

  14. An in vivo zebrafish screen identifies organophosphate antidotes with diverse mechanisms of action.

    PubMed

    Jin, Shan; Sarkar, Kumar S; Jin, Youngnam N; Liu, Yan; Kokel, David; Van Ham, Tjakko J; Roberts, Lee D; Gerszten, Robert E; Macrae, Calum A; Peterson, Randall T

    2013-01-01

    Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a high priority. Early life stage zebrafish exposed to organophosphates exhibit several phenotypes that parallel the human response to organophosphates, including behavioral deficits, paralysis, and eventual death. Here, we have developed a high-throughput zebrafish screen in a 96-well plate format to find new antidotes that counteract organophosphate-induced lethality. In a pilot screen of 1200 known drugs, we identified 16 compounds that suppress organophosphate toxicity in zebrafish. Several in vitro assays coupled with liquid chromatography/tandem mass spectrometry-based metabolite profiling enabled determination of mechanisms of action for several of the antidotes, including reversible acetylcholinesterase inhibition, cholinergic receptor antagonism, and inhibition of bioactivation. Therefore, the in vivo screen is capable of discovering organophosphate antidotes that intervene in distinct pathways. These findings suggest that zebrafish screens might be a broadly applicable approach for discovering compounds that counteract the toxic effects of accidental or malicious poisonous exposures.

  15. An In Vivo Zebrafish Screen Identifies Organophosphate Antidotes with Diverse Mechanisms of Action

    PubMed Central

    Jin, Shan; Sarkar, Kumar S.; Jin, Youngnam N.; Liu, Yan; Kokel, David; Van Ham, Tjakko J.; Roberts, Lee D.; Gerszten, Robert E.; MacRae, Calum A.; Peterson, Randall T.

    2014-01-01

    Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a high priority. Early life stage zebrafish exposed to organophosphates exhibit several phenotypes that parallel the human response to organophosphates, including behavioral deficits, paralysis, and eventual death. Here, we have developed a high-throughput zebrafish screen in a 96-well plate format to find new antidotes that counteract organophosphate-induced lethality. In a pilot screen of 1200 known drugs, we identified 16 compounds that suppress organophosphate toxicity in zebrafish. Several in vitro assays coupled with liquid chromatography/tandem mass spectrometry–based metabolite profiling enabled determination of mechanisms of action for several of the antidotes, including reversible acetylcholinesterase inhibition, cholinergic receptor antagonism, and inhibition of bioactivation. Therefore, the in vivo screen is capable of discovering organophosphate antidotes that intervene in distinct pathways. These findings suggest that zebrafish screens might be a broadly applicable approach for discovering compounds that counteract the toxic effects of accidental or malicious poisonous exposures. PMID:22960781

  16. Organophosphate poisoning in a 12-day-old infant: case report.

    PubMed

    O'Reilly, D A; Heikens, G T

    2011-01-01

    A 12-day-old infant girl was admitted with increasing lethargy and respiratory distress. Initial treatment was for pneumonia but deterioration despite appropriate treatment prompted review of her diagnosis and consideration of organophosphate poisoning. There was a brisk response to atropine. To our knowledge, this is the youngest infant reported to have been exposed to poisoning by organophosphates.

  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. Application of ultraperformance liquid chromatography/mass spectrometry-based metabonomic techniques to analyze the joint toxic action of long-term low-level exposure to a mixture of organophosphate pesticides on rat urine profile.

    PubMed

    Du, Longfei; Wang, Hong; Xu, Wei; Zeng, Yan; Hou, Yurong; Zhang, Yuqiu; Zhao, Xiujuan; Sun, Changhao

    2013-07-01

    In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) to rats using metabonomic technology at their corresponding no observed adverse effect level (NOAEL). Results show that a single pesticide elicits no toxic response. This study aimed to determine whether chronic exposure to a mixture of the above four pesticides (at their corresponding NOAEL) can lead to joint toxic action in rats using the same technology. Pesticides were administered daily to rats through drinking water for 24 weeks. The above mixture of the four pesticides showed joint toxic action at the NOAEL of each pesticide. The metabonomic profiles of rats urine were analyzed by ultraperformance liquid chromatography/mass spectrometry. The 16 metabolites statistically significantly changed in all treated groups compared with the control group. Dimethylphosphate and dimethyldithiophosphate exclusively detected in all treated groups can be used as early, sensitive biomarkers for exposure to a mixture of the OP pesticides. Moreover, exposure to the OP pesticides resulted in increased 7-methylguanine, ribothymidine, cholic acid, 4-pyridoxic acid, kynurenine, and indoxyl sulfate levels, as well as decreased hippuric acid, creatinine, uric acid, gentisic acid, C18-dihydrosphingosine, phytosphingosine, suberic acid, and citric acid. The results indicated that a mixture of OP pesticides induced DNA damage and oxidative stress, disturbed the metabolism of lipids, and interfered with the tricarboxylic acid cycle. Ensuring food safety requires not only the toxicology test data of each pesticide for the calculation of the acceptable daily intake but also the joint toxic action.

  19. How to Form a Food Co-op.

    ERIC Educational Resources Information Center

    Dodge, Philip; And Others

    Based on questions asked during an adult education course at Truman College (Chicago), this booklet was designed to be a simple organizing manual for small neighborhood preorder food cooperatives (co-ops). The guide covers basic information for organizing a co-op, definition of a co-op, what jobs are needed, getting the food, wholesale sources,…

  20. 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

  1. Studies on the Enzymatic Hydrolysis of Organophosphate Poisons in Pigs.

    DTIC Science & Technology

    1982-11-01

    Idantlty by Woe« numb«-; Hydrolysis Of the OrganO- phosphate paraoxon was studied in Yorkshire pig, rat and human sera. Enzymatic hydrolysis ...D-A123 269 UNCLASSIFIED STUDIES ON THE ENZYMATIC HYDROLYSIS OF ORGflNOPHOSPHATE 1/i POISONS IN PIGS(U) LETTERNAN ARMY INST OF RESEARCH...ON THE ENZYMATIC HYDROLYSIS OF ORGANOPHOSPHATE POISONS IN PIGS Part 1. pH and Ion Effects in Sera from Pigs, Rats, and Humans PETER SCHMID, PhD

  2. Joint SatOPS Compatibility Efforts

    NASA Technical Reports Server (NTRS)

    Smith, Danford

    2010-01-01

    This slide presentation reviews NASA Goddard Space Flight Center's (GSFC) participation in the interagency cooperation committee, the Joint SatOps Compatibility Committee (JSCC), and the compatible Sat 2 efforts. Part of GSFC's participation in the JSCC is to work with the Goddard Mission Systems Evolution Center (GMSEC) to provides a publish/subscribe framework to enable rapid integration of commercially available satellite control products.

  3. Thermal desorption-gas chromatography-mass spectrometry method to determine phthalate and organophosphate esters from air samples.

    PubMed

    Aragón, M; Borrull, F; Marcé, R M

    2013-08-16

    A method based on thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) has been developed to determine four organophosphate esters, seven phthalate esters, and bis(2-ethylhexyl) adipate in the gas phase from harbour and urban air samples. The method involves the sampling of 1.5L of air in a Tenax TA sorbent tube followed by thermal desorption (using a Tenax TA cryogenic trap) coupled to gas chromatography-mass spectrometry. The repeatability of the method expressed as %RSD (n=3) is less than 15% and the MQLs are between 0.007μgm(-3) (DMP, TBP, BBP, TPP and DnOP) and 6.7μgm(-3) (DEHP). The method was successfully applied in two areas (urban and harbour) testing two and three points in each one, respectively. Some of these compounds were found in both urban and harbour samples. Di-(2-ethylhexyl)phthalate was the most abundant compound found in both areas at concentration levels between 6.7μgm(-3) and 136.4μgm(-3). This study demonstrates that thermal desorption is an efficient method for the determination of these semi-volatile compounds in the gas phase fraction of air samples.

  4. 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.

  5. Use of cholinesterase activity in monitoring organophosphate pesticide exposure of cattle produced in tropical areas.

    PubMed

    Pardío, V T; Ibarra, N; Rodríguez, M A; Waliszewski, K N

    2001-12-01

    The use of cholinesterase activity as a biochemical method for monitoring organophosphate pesticide exposure in cattle is described herein. Determination of cholinesterase activity of whole blood, erythrocyte, and plasma was carried out according to the Ellman modified kinetic method. The mean baseline acetylcholinesterase activities of 9.549 +/- 3.619 IU/mL in whole blood, 9.444 +/- 3.006 IU/mL in erythrocytes, and 0.149 +/- 0.063 IU/mL in plasma were estimated for steers from the control group. Results of multivariate analysis showed that the general responses between the control and experimental groups (in vivo, monitoring and case studies) treated with Coumaphos and Fenthion were statistically different, and the general responses of these experimental groups were statistically different over time as well. Among the fractions that were analyzed, the erythrocyte acetylcholinesterase activity could be adequate for the diagnosis of exposure or acute poisoning in cattle as it showed a good within-run and between-run precision with CVs <10% better than those in plasma.

  6. A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology

    PubMed Central

    Mullen, Brian R.; Ross, Brennan; Chou, Joan Wang; Khankan, Rana; Khialeeva, Elvira; Bui, Kimberly

    2016-01-01

    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. PMID:27364165

  7. Sensitivity of Costa Rica's native cladoceran Daphnia ambigua and Simocephalus serrulatus to the organophosphate pesticide ethoprophos.

    PubMed

    Arias-Andrés, María; Torres, Freylan Mena; Vargas, Seiling; Solano, Karla

    2014-01-01

    The study of pesticide toxicity in aquatic environments is assessed with ecotoxicological tests and most research has been performed using species from temperate regions. In the present study, series of acute (48 hrs) toxicity tests to compare the sensibility of two indigenous cladocera of Costa Rica and two reference species were used in temperate regions to the organophosphate pesticide, Ethoprophos. Additionally, reproduction tests using S. serrulatus with sub lethal concentrations of ethoprophos and a control were assayed to check its sensitivity over a longer period exposure. The sensitivity of Costa Rica's native species Daphnia ambigua (EC50 48 hr: 12.9 +/- 3.0 microg(l(-1)) and Simocephalus serrulatus (10.6 +/- 2.1 microg l(-1)) to ethoprophos were higher (p < 0.05) when compared to the exotic species Daphnia magna (289.8 +/- 77.4 microg l(-1)), and were comparable to that of the more widely distributed species, Ceriodaphnia dubia (18.2 +/- 5.2 microg l(-1)). No effect on S. serrulatus reproduction was observed at concentrations between 1 and 4 microg l(-1). This study provides information that can be considered in the selection of species for ecosystem studies of pesticide toxicity in neotropical regions.

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

    SciTech Connect

    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) 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.

  9. Expression of organophosphate hydrolase in the filamentous fungus Gliocladium virens.

    PubMed

    Dave, K I; Lauriano, C; Xu, B; Wild, J R; Kenerley, C M

    1994-05-01

    The broad-spectrum organophosphate hydrolase (OPH; EC 3.1.8.1) encoded by the organophosphate-degrading gene (opd) from Pseudomonas diminuta MG and Flavobacterium sp. ATCC 27551 possesses capabilities of both P-O bond hydrolysis (e.g. paraoxon) and P-F bond hydrolysis [e.g. sarin and diisopropylfluorophosphate (DFP)]. In the present study a 9.4-kb plasmid, pCL1, was used to transform the saprophytic fungus Gliocladium virens. pCL1 was derived from pJS294 by placing the fungal promoter (prom1) from Cochliobolus heterostrophus upstream and the trpC terminator from Aspergillus nidulans down-stream of the opd gene. Southern analysis of restricted genomic DNA from various transformants indicated that integration occurred non-specifically at multiple sites. Western blot analysis of mycelial extracts from transformants confirmed the production of a processed form of the enzyme in the fungus. Maximal levels of OPH activity (rate of p-nitrophenol production from paraoxon) were observed after 168 h of culture and activity levels correlated with biomass production in mature vegetative growth.

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

    SciTech Connect

    Wang, Hua; Wang, Jun; Choi, Daiwon; Tang, Zhiwen; Wu, Hong; Lin, Yuehe

    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 accumulation 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.

  11. Toxicological assessment of isomeric pesticides: a strategy for testing of chiral organophosphorus (OP) compounds for delayed polyneuropathy in a regulatory setting.

    PubMed

    Battershill, Jon M; Edwards, Philippa M; Johnson, Martin K

    2004-08-01

    Many compounds, including some pesticides, contain structural centres of asymmetry, which convey the property of a type of stereoisomerism known as chirality. Such compounds can exist in two or more forms, depending on the number of chiral atoms and are termed stereoisomers or enantiomers. Stereoisomers of a particular compound can have different biological properties; one such of particular importance for toxicological evaluation, is the potential for differences in metabolic disposal of and binding of stereoisomers to molecular targets in the cell. The combination of differential metabolism of chiral organophosphorus (OP) pesticides and opposing stereoselectivity of inhibition of neuropathy target esterase (NTE) and acetylcholinesterase (AChE) can affect the value of the hen test, performed to OECD guidelines, in predicting the potential to cause organophosphate-induced delayed polyneuropathy (OPIDP) in humans. This is a mixed central and sensory and motor neuropathy. The experimental data on structural analogues of the pesticide methamidophos and the evidence for stereoselective OPIDP are reviewed and a model is given demonstrating how the properties of a chiral OP can result in the neuropathic potential not being detected by the standard hen test. A strategy for the assessment of a racemic mixture comprised of two OP enantiomers for the potential to induce OPIDP is outlined. The strategy uses information from structure activity relationships (SAR), in vitro tests and in vivo tests to allow risk assessment decisions to be made. It is suggested that the potential for stereoselective toxicity of pesticides should be routinely considered in regulatory assessments.

  12. 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

  13. 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.

  14. Tempel 1 First Op-Nav

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Tempel 1 First Optical Navigation

    On Monday, April 25, the Deep Impact spacecraft obtained its first optical navigation (Op-Nav) image of comet Tempel 1. At the time the picture was taken the distance between spacecraft and comet was 64 million kilometers (39.7 million miles) away. The exposure -- known as a 'negative image' -- is used by the spacecraft team to assist in navigation and instrument calibration. The spacecraft will start imaging the comet on a regular basis in about 10 days.

  15. 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...

  16. 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...

  17. 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...

  18. High sensitive self-assembled monolayer modified solid mounted resonator for organophosphate vapor detection

    NASA Astrophysics Data System (ADS)

    Wang, Jingjing; Chen, Da; Gan, Yaoguo; Sun, Xuejun; Jin, Yingying

    2011-02-01

    We fabricated a self-assembled monolayer (SAM) modified solid mounted resonator (SMR) for organophosphate vapor detection. The SMR device consisted of a piezoelectric stack and an all-metal Bragg's reflector. The electrode surface is chemically modified with a Cu2+/11-mercaptoundecanoic acid SAM to capture organophosphate compounds. After chemical modification, both the resonance frequency and the Q-factor decrease. Fourier transform infrared external reflection spectroscopy was performed to verify the formation of SAM. Adsorption of organophosphate compounds onto the SAM increases its mass, and the resonance frequency proportionally goes down. The testing results show that the modified SMR can yield a rapid, sensitive, reversible and reproducible response to nerve-agent (dimethyl methyl phosphonate) vapor. This study proves that using the SAM modified SMR to detect trace organophosphate vapor is feasibility.

  19. 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...

  20. 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...

  1. In vitro inhibition of acetylcholinesterase from four marine species by organophosphates and carbamates

    SciTech Connect

    Galgani, F.; Bocquene, G. )

    1990-08-01

    The literature on the biological, physical, and pharmaceutical chemistry of cholinesterase is considerable and includes data on activators and inhibitors. Most of the work on specific anticholinesterasic agents has been concerned with carbamates and organophosphates. Because of the sensitivity of acetylcholinesterase to carbamates and organophosphates, the enzyme has been used as a biochemical indicator of pollution by these agents. However, the chemical reactivity of such chemicals has not been correlated with their effect on Ache and it is impossible to accurately predict biological effects based only on structure. The objectives of this study were to investigate the sensitivity of various marine animals to both organo-phosphates and carbamates. The study was conducted by assessing the in vitro effect of five organophosphates and three carbamates on acetylcholinesterase activity from the muscle of the shrimp Palaemon serratus, the fishes Scomber and Pleuronectes platessa, and from the whole mussels Mytilus edulis. All these species could be used for the monitoring of effect of pollutants.

  2. 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.

  3. Organophosphate flame retardants and plasticisers in wastewater treatment plants.

    PubMed

    Meyer, J; Bester, K

    2004-07-01

    Previous studies have revealed that chlorinated and non-chlorinated organophosphorous flame retardants and plasticisers are important contaminants in German surface waters and it has been demonstrated that wastewater treatment plants contribute to the emission of these substances. In this study temporal development as well as elimination efficiency were determined in two wastewater treatment plants (STP) in the Ruhr/Rhine area at different stages of the wastewater treatment process. The samples were analysed for the non-chlorinated organophosphate esters tri-n-butylphosphate (TnBP), tri-iso-butylphosphate (TiBP), tris-(butoxyethyl)-phosphate (TBEP) and triphenylphosphate (TPP) and the chlorinated organophosphate esters tris-(2-chloro, 1-methylethyl)-phosphate (TCPP), tris-(2-chloro-, 1-chloromethylethyl)-phosphate (TDCP) and tris-(2-chloroethyl)-phosphate (TCEP). The study showed that there were significant differences in the elimination of chlorinated and non-chlorinated organophosphorous flame retardants. The elimination rates ranged from 57-86% for TiBP, TnBP and TBEP at both STP's. No elimination of the chlorinated flame retardants TCPP, TDCP and TCEP was observed in any of the sampled STPs. At both STPs the first treatment steps and the final filtration did not contribute to the elimination of the non-chlorinated organophosphorous flame retardants while the aeration step did. At both STPs the efficiency of the cleaning process concerning the flame retardants was comparable. Thus the type of construction of the STP was not relevant for the elimination of these substances. Additionally a strong day-to-day variation was observed, while in one STP a temporal trend for TCPP during the week was found.

  4. Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes).

    PubMed

    Sun, Liwei; Tan, Hana; Peng, Tao; Wang, Sisi; Xu, Wenbin; Qian, Haifeng; Jin, Yuanxiang; Fu, Zhengwei

    2016-12-01

    Because brominated flame retardants are being banned or phased out worldwide, organophosphate flame retardants have been used as alternatives on a large scale and have thus become ubiquitous environmental contaminants; this raises great concerns about their environmental health risk and toxicity. Considering that previous research has identified the nervous system as a sensitive target, Japanese medaka were used as an aquatic organism model to evaluate the developmental neurotoxicity of 4 organophosphate flame retardants: triphenyl phosphate, tri-n-butyl phosphate, tris(2-butoxyethyl) phosphate, and tris(2-chloroethyl) phosphate (TCEP). The embryo toxicity test showed that organophosphate flame retardant exposure could decrease hatchability, delay time to hatching, increase the occurrence of malformations, reduce body length, and slow heart rate. Regarding locomotor behavior, exposure to the tested organophosphate flame retardants (except TCEP) for 96 h resulted in hypoactivity for medaka larvae in both the free-swimming and the dark-to-light photoperiod stimulation test. Changes of acetylcholinesterase activity and transcriptional responses of genes related to the nervous system likely provide a reasonable explanation for the neurobehavioral disruption. Overall, the present study clearly demonstrates the developmental neurotoxicity of various organophosphate flame retardants with very different potency and contribute to the determination of which organophosphate flame retardants are appropriate substitutes, as well as the consideration of whether regulations are reasonable and required. Environ Toxicol Chem 2016;35:2931-2940. © 2016 SETAC.

  5. CSF-1 deficiency in the op/op mouse has differential effects on macrophage populations and differentiation stages.

    PubMed

    Wiktor-Jedrzejczak, W; Ratajczak, M Z; Ptasznik, A; Sell, K W; Ahmed-Ansari, A; Ostertag, W

    1992-09-01

    Osteopetrosis and the absence of colony-stimulating factor 1 (CSF-1) in op/op mice are associated with decreased cellularity of the bone marrow (to one tenth of the normal), a very significant reduction in the number of cells recovered from peritoneal, pleural, and alveolar lavages, moderate leukopenia, and a slight decrease in the number of cells per spleen and thymus. Furthermore, op/op mice possess deficiencies in the number of macrophages in various organs. These cells are apparently absent in the bone marrow, severely reduced (5%-15% of the normal number) in peritoneal and pleural cavities and in the lungs. In addition, a marked decrease in the frequency and total number of circulating monocytes is present (5% of the normal). The deficiency of macrophages is less severe in the liver, spleen, and thymus of op/op mice (approximately 30% of those seen in normal). There is a concomitant redistribution of macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) in op/op mice from the marrow to the spleen and liver, associated with an increased sensitivity to interleukin 3 (IL-3). Their total number is decreased at least threefold compared to control mice. Moreover, op/op mice have at least a fivefold reduction in the total number of day-11 spleen colony-forming units (CFU-S) associated with their redistribution to the spleen and liver. These data suggest that the macrophage system in op/op mice is reduced at all levels tested, that is, at the level of mature macrophages, the level of progenitors, and the level of stem cells, whereas the redistribution of progenitor and stem cells could be viewed as a secondary consequence of osteopetrosis. Furthermore, these data suggest that macrophage dependency in vivo on CSF-1 is limited and different in various organs. Particularly in the liver, spleen, and thymus, other growth factors may significantly compensate for CSF-1 deficiency. Based on the relative decrease in the number of CFU-GM in the op/op

  6. VEP Responses to Op-Art Stimuli

    PubMed Central

    O’Hare, Louise; Clarke, Alasdair D. F.; Pollux, Petra M. J.

    2015-01-01

    Several types of striped patterns have been reported to cause adverse sensations described as visual discomfort. Previous research using op-art-based stimuli has demonstrated that spurious eye movement signals can cause the experience of illusory motion, or shimmering effects, which might be perceived as uncomfortable. Whilst the shimmering effects are one cause of discomfort, another possible contributor to discomfort is excessive neural responses: As striped patterns do not have the statistical redundancy typical of natural images, they are perhaps unable to be encoded efficiently. If this is the case, then this should be seen in the amplitude of the EEG response. This study found that stimuli that were judged to be most comfortable were also those with the lowest EEG amplitude. This provides some support for the idea that excessive neural responses might also contribute to discomfort judgements in normal populations, in stimuli controlled for perceived contrast. PMID:26422207

  7. Multifunctional drugs as novel antidotes for organophosphates' poisoning.

    PubMed

    Weissman, Ben Avi; Raveh, Lily

    2011-12-18

    Some organophosphorus compounds (OPs) are nerve agents that continue to concern military personnel and civilians as potential battlefield and terrorist threats. Additionally, OPs are used in agriculture where they are associated with numerous cases of intentional and accidental misuse. These toxicants induce an array of deleterious effects including respiratory distress, convulsions and ultimately death. A mechanism involving a rapid and potent inhibition of peripheral and central cholinesterases leading to a massive buildup of acetylcholine in synaptic clefts was suggested as the underlying trigger of the toxic events. Indeed, therapy comprised of an acetylcholinesterase reactivator (i.e., oxime) and a cholinergic antagonist (e.g., atropine) is the accepted major paradigm for protection. This approach yields a remarkable survival rate but fails to prevent neurological and behavioral deficits. Extensive research revealed a complex picture consisting of an early activation of several neurotransmitter systems, in which the glutamatergic plays a pivotal role., Data accumulated in recent years support the concept that multi-targeting of pathways including glutamatergic and cholinergic circuits is required for an effective treatment. Drugs that demonstrate the ability to interact with several systems (e.g., caramiphen) were found to afford a superior protection against OPs as compared to specific antimuscarinic ligands (e.g., scopolamine). Compounds that potently block muscarinic receptors, interact with the NMDA ion channel and in addition are able to modulate σ(1) sites and/or GABAergic transmission seem to represent the emerging backbone for novel antidotes against OP poisoning. Several multifunctional drugs are already used for complex diseases e.g., cancer and depression.

  8. 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...

  9. 2011 Internship & Co-Op Survey. Research Brief

    ERIC Educational Resources Information Center

    National Association of Colleges and Employers (NJ1), 2011

    2011-01-01

    The National Association of Colleges and Employers' (NACE's) "2011 Internship & Co-op Survey" indicates that internships are an integral and ever-important part of the college recruiting scene. The survey finds that employers expect to increase internship hiring by about 7 percent this year and co-op positions by nearly 9 percent. Furthermore,…

  10. Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community

    PubMed Central

    Huen, Karen; Bradman, Asa; Harley, Kim; Yousefi, Paul; Barr, Dana Boyd; Eskenazi, Brenda; Holland, Nina

    2014-01-01

    Organophosphate pesticides are widely used and recent studies suggest associations of in utero exposures with adverse birth outcomes and neurodevelopment. Few studies have characterized organophosphate pesticides in human plasma or established how these levels correlate to urinary measurements. We measured organophosphate pesticide metabolites in maternal urine and chlorpyrifos and diazinon in maternal and cord plasma of subjects living in an agricultural area to compare levels in two different biological matrices. We also determined paraoxonase 1 (PON1) genotypes (PON1192 and PON1-108) and PON1 substrate-specific activities in mothers and their newborns to examine whether PON1 may affect organophosphate pesticide measurements in blood and urine. Chlorpyrifos levels in plasma ranged from 0-1726 ng/mL and non-zero levels were measured in 70.5% and 87.5% of maternal and cord samples, respectively. Diazinon levels were lower (0-0.5 ng/mL); non-zero levels were found in 33.3% of maternal plasma and 47.3% of cord plasma. Significant associations between organophosphate pesticide levels in blood and metabolite levels in urine were limited to models adjusting for PON1 levels. Increased maternal PON1 levels were associated with decreased odds of chlorpyrifos and diazinon detection (odds ratio(OR): 0.56 and 0.75, respectively). Blood organophosphate pesticide levels of study participants were similar in mothers and newborns and slightly higher than those reported in other populations. However, compared to their mothers, newborns have much lower quantities of the detoxifying PON1 enzyme suggesting that infants may be especially vulnerable to organophosphate pesticide exposures. PMID:22683313

  11. Para Niños Saludables: A Community Intervention Trial to Reduce Organophosphate Pesticide Exposure in Children of Farmworkers

    PubMed Central

    Thompson, Beti; Coronado, Gloria D.; Vigoren, Eric M.; Griffith, William C.; Fenske, Richard A.; Kissel, John C.; Shirai, Jeffry H.; Faustman, Elaine M.

    2008-01-01

    Background Exposure to organophosphate (OP) pesticides is an occupational hazard for farmworkers and affects their children through the take-home pathway. Objectives We examined the effectiveness of a randomized community intervention to reduce pesticide exposure among farmworkers and their children. Methods We conducted a baseline survey of a cross-sectional sample of farmworkers (year 1) in 24 participating communities. Communities were randomized to intervention or control. After 2 years of intervention, a new cross-sectional survey of farmworkers was conducted (year 4). Farmworkers with a child 2–6 years of age were asked to participate in a substudy in which urine was collected from the farmworker and child, and dust was collected from the home and the vehicle driven to work. Results The median concentration of urinary metabolites was higher in year 4 than in year 1 for dimethylthiophosphate (DMTP) and dimethyldithiophosphate in adults and for DMTP for children. There were significant increases within both the intervention and control communities between year 1 and year 4 (p < 0.005); however, the differences were not significant between study communities after adjusting for year (p = 0.21). The dust residue data showed azinphos-methyl having the highest percentage of detects in vehicles (86% and 84% in years 1 and 4, respectively) and in house dust (85% and 83% in years 1 and 4, respectively). There were no significant differences between intervention and control communities after adjusting for year (p = 0.49). Conclusions We found no significant decreases in urinary pesticide metabolite concentrations or in pesticide residue concentrations in house and vehicle dust from intervention community households compared with control community households after adjusting for baseline. These negative findings may have implications for future community-wide interventions. PMID:18470300

  12. Co-op Essay - Tour 1

    NASA Technical Reports Server (NTRS)

    Porter, Derrick

    2014-01-01

    The Mission Operations Directorate (MOD) is responsible for the training, planning and performance of all U.S. manned operations in space. Within this directorate all responsibilities are divided up into divisions. The EVA, Robotics & Crew Systems Operations Division performs ground operations and trains astronauts to carry out some of the more "high action" procedures in space. For example they orchestrate procedures like EVAs, or ExtraVehicular Activities (spacewalks), and robotics operations external to the International Space Station (ISS). The robotics branch of this division is responsible for the use of the Mobile Servicing System (MSS). This system is a combination of two robotic mechanisms and a series of equipment used to transport them on the ISS. The MSS is used to capture and position visiting vehicles, transport astronauts during EVAs, and perform external maintenance tasks on the ISS. This branch consists of two groups which are responsible for crew training and flight controlling, respectively. My first co-op tour took place Fall 2013. During this time I was given the opportunity to work in the robotics operations branch of the Mission Operations Directorate at NASA's Johnson Space Center. I was given a variety of tasks that encompassed, at a base level, all the aspects of the branch.

  13. Occurrence of organophosphate flame retardants in drinking water from China.

    PubMed

    Li, Jun; Yu, Nanyang; Zhang, Beibei; Jin, Ling; Li, Meiying; Hu, Mengyang; Zhang, Xiaowei; Wei, Si; Yu, Hongxia

    2014-05-01

    Several organophosphate flame retardants (OPFRs) have been identified as known or suspected carcinogens or neurotoxic substances. Given the potential health risks of these compounds, we conducted a comprehensive survey of nine OPFRs in drinking water in China. We found total concentrations of OPFRs in tap water ranging from 85.1 ng/L to 325 ng/L, and tris(2-butoxyethyl) phosphate (TBEP), triphenyl phosphate (TPP), and tris(2-chloroisopropyl) phosphate (TCPP) were the most common components. Similar OPFR concentrations and profiles were observed in water samples processed through six different waterworks in Nanjing, China. However, boiling affected OPFR levels in drinking water by either increasing (e.g., TBEP) or decreasing (e.g., tributyl phosphate, TBP) concentrations depending on the particular compound and the state of the indoor environment. We also found that bottled water contained many of the same major OPFR compounds with concentrations 10-25% lower than those in tap water, although TBEP contamination in bottled water remained a concern. Finally, we concluded that the risk of ingesting OPFRs through drinking water was not a major health concern for either adults or children in China. Nevertheless, drinking water ingestion represents an important exposure pathway for OPFRs.

  14. Prenatal exposure to the organophosphate pesticide chlorpyrifos and childhood tremor

    PubMed Central

    Rauh, Virginia A.; Garcia, Wanda E.; Whyatt, Robin M.; Horton, Megan K.; Barr, Dana B.; Louis, Elan D.

    2016-01-01

    Background The organophosphate insecticide chlorpyrifos (CPF), widely used for agricultural purposes, has been linked to neurodevelopmental deficits. Possible motor effects at low to moderate levels of exposure have not been evaluated. Methods Prenatal exposure to CPF was measured in umbilical cord blood in a sample of 263 inner-city minority children, who were followed prospectively. At approximately 11 years of age (mean age 10.9 ± 0.85 years, range = 9.0–13.9), during a neuropsychological assessment, children were asked to draw Archimedes spirals. These were rated by a senior neurologist specializing in movement disorders who was blind to CPF exposure level. Results Compared to all other children, those with prenatal CPF exposure in the upper quartile range (n = 43) were more likely to exhibit mild or mild to moderate tremor (≥1) in either arm (p = 0.03), both arms (p = 0.02), the dominant arm (p = 0.01), and the non-dominant arm (p = 0.055). Logistic regression analyses showed significant CPF effects on tremor in both arms, either arm, the dominant arm (p-values < 0.05), and the non-dominant arm (p = 0.06), after adjustment for sex, age at testing, ethnicity, and medication. Conclusion Prenatal CPF exposure is associated with tremor in middle childhood, which may be a sign of the insecticide's effects on nervous system function. PMID:26385760

  15. Organophosphate Esters in Sediment of the Great Lakes.

    PubMed

    Cao, Dandan; Guo, Jiehong; Wang, Yawei; Li, Zhuona; Liang, Kang; Corcoran, Margaret B; Hosseini, Soheil; Bonina, Solidea M C; Rockne, Karl J; Sturchio, Neil C; Giesy, John P; Liu, Jingfu; Li, An; Jiang, Guibin

    2017-02-07

    This is the first study on organophosphate ester (OPEs) flame retardants and plasticizers in the sediment of the Great Lakes. Concentrations of 14 OPEs were measured in three sediment cores and 88 Ponar surface grabs collected from Lakes Ontario, Michigan, and Superior of North America. The sum of these OPEs (Σ14OPEs) in Ponar grabs averaged 2.2, 4.7, and 16.6 ng g(-1) dw in Lakes Superior, Michigan, and Ontario, respectively. Multiple linear regression analyses demonstrated statistically significant associations between logarithm concentrations of Σ14OPEs as well as selected congeners in surface grab samples and sediment organic carbon content as well as a newly developed urban distance factor. Temporal trends observed in dated sediment cores from Lake Michigan demonstrated that the recent increase in depositional flux to sediment is dominated by chlorinated OPEs, particularly tris(2-chloroisopropyl) phosphate (TCPP), which has a doubling time of about 20 years. Downward diffusion within sediment may have caused vertical fractionation of OPEs over time. Two relatively hydrophilic OPEs including TCPP had much higher concentrations in sediment than estimated based on equilibria between water and sediment organic carbon. Approximately a quarter (17 tonnes) of the estimated total OPE burden (63 tonnes) in Lake Michigan resides in sediment, which may act as a secondary source releasing OPEs to the water column for years to come.

  16. Estimates of Tiber River organophosphate pesticide loads to the Tyrrhenian Sea and ecological risk.

    PubMed

    Montuori, Paolo; Aurino, Sara; Garzonio, Fatima; Sarnacchiaro, Pasquale; Polichetti, Salvatore; Nardone, Antonio; Triassi, Maria

    2016-07-15

    The organophosphate pesticides pollution in the Tiber River and its environmental impact on the Tyrrhenian Sea (Central Mediterranean Sea) were estimated. Eight selected organophosphate pesticides (diazinon, dimethoate, malathion, chlorpyrifos, pirimiphos-methyl, fenitrothion, methidathion, tolclofos-methyl) were determined in the water dissolved phase, suspended particulate matter and sediment samples collected from 21 sites in different seasons. Total organophosphate pesticides concentrations ranged from 0.40 to 224.48ngL(-1) in water (as the sum of the water dissolved phase and suspended particulate matter) and from 1.42 to 68.46ngg(-1) in sediment samples. Contaminant discharges of organophosphate pesticides into the sea were calculated in about 545.36kgyear(-1) showing that this river should be consider as one of the main contribution sources of organophosphate pesticides to the Tyrrhenian Sea. In relation to the eco-toxicological assessment, the concentrations of most OPPs in the water and sediments from the Tiber River and its estuary were lower than guideline values.

  17. 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

  18. Comparative cost-effectiveness of ivermectin versus topical organophosphate in feedlot calves

    PubMed Central

    Bauck, Stewart W.; Jim, G. Kee; Guichon, P. Tim; Newcomb, Kathleen M.; Cox, James L.; Barrick, Ruth-Ann

    1989-01-01

    A study was conducted in a commercial feedlot in western Canada to evaluate the impact of treatment with ivermectin versus a topical organophosphate on growth rate and feed efficiency in calves entering a feedlot at an average 275 kg liveweight. A total of 9527 head of cattle was used. Variables measured included average daily gain, average days occupation, and feed conversion. Ivermectin treated animals gained an average 0.08 kg per day more than those treated with topical organophosphate. In addition, they required an average 0.23 kg less feed/kg gain. Based on an average 227 kg of gain, this would result in 11 fewer days occupation and 52.3 kg less feed for ivermectin treated animals. This equaled a net benefit of $7.04 per head over treatment costs for ivermectin treatment versus topical organophosphate. PMID:17423237

  19. Optimal sensor placement for detecting organophosphate intrusions into water distribution systems.

    PubMed

    Ohar, Ziv; Lahav, Ori; Ostfeld, Avi

    2015-04-15

    Placement of water quality sensors in a water distribution system is a common approach for minimizing contamination intrusion risks. This study incorporates detailed chemistry of organophosphate contaminations into the problem of sensor placement and links quantitative measures of the affected population as a result of such intrusions. The suggested methodology utilizes the stoichiometry and kinetics of the reactions between organophosphate contaminants and free chlorine for predicting the number of affected consumers. This is accomplished through linking a multi-species water quality model and a statistical dose-response model. Three organophosphates (chlorpyrifos, malathion, and parathion) are tested as possible contaminants. Their corresponding by-products were modeled and accounted for in the affected consumers impact calculations. The methodology incorporates a series of randomly generated intrusion events linked to a genetic algorithm for minimizing the contaminants impact through a sensors system. Three example applications are explored for demonstrating the model capabilities through base runs and sensitivity analyses.

  20. Dorothy Jorgensen - Co-Op Tour Summary

    NASA Technical Reports Server (NTRS)

    Jorgensen, Dorothy

    2014-01-01

    NASA is a household name in this day and age, known commonly as America's government-run powerhouse of innovation and space exploration. It is a common dream for students to be a part of NASA's workforce, but I did not realize that it was my dream until I found that I could not imagine working anywhere else. From August to December, I had the privilege of a co-op tour with NASA at the Johnson Space Center. The National Aeronautics and Space Administration (NASA) first formed in the early hysteria of the Cold War, and in its early days it received enormous funding and political support. It was America's response to the Russian Sputnik, which was a not only a stark symbol of what was suddenly possible, but also of how far behind the United States had fallen in the race for technology. The political atmosphere in the world has since changed, but NASA's drive to push the boundaries of the impossible has not faded: NASA's primary mission has been exploration for the betterment of mankind, and it works towards that mission to this day. The specific NASA site that I worked in was by a coast near Houston, TX, at the Johnson Space Center (Figure 1). I was led on my first day of work to a building dedicated to Structural Engineering (Building 13), which was where I would be spending most of my time in the months to come. It was here that I had my desk and cubicle, and would later do the bulk of my computer modeling and theoretical planning. Later that day we traveled to the Vibrations and Acoustics Test Facility (Building 49), and here I was shown the parts we would use for our technical project and the locations we would work in. I worked in the Loads and Dynamics Branch of the Structural Engineering Division, in the Engineering Directorate.

  1. DRACO: Didymos Reconnaissance and Asteroid Camera for Op-Nav

    NASA Astrophysics Data System (ADS)

    Fletcher, Z. J.; Cheng, A. F.; Barnouin, O. S.; Chabot, N. L.; Reed, C. L.

    2016-10-01

    The proposed DART mission is the first demonstration of kinetic impact for deflection of an asteroid. We describe DART's instrument DRACO's (Didymos Reconaissance and Asteroid Camera for Op-nav) requirements, resulting design, and planned operations.

  2. OP-ELM: optimally pruned extreme learning machine.

    PubMed

    Miche, Yoan; Sorjamaa, Antti; Bas, Patrick; Simula, Olli; Jutten, Christian; Lendasse, Amaury

    2010-01-01

    In this brief, the optimally pruned extreme learning machine (OP-ELM) methodology is presented. It is based on the original extreme learning machine (ELM) algorithm with additional steps to make it more robust and generic. The whole methodology is presented in detail and then applied to several regression and classification problems. Results for both computational time and accuracy (mean square error) are compared to the original ELM and to three other widely used methodologies: multilayer perceptron (MLP), support vector machine (SVM), and Gaussian process (GP). As the experiments for both regression and classification illustrate, the proposed OP-ELM methodology performs several orders of magnitude faster than the other algorithms used in this brief, except the original ELM. Despite the simplicity and fast performance, the OP-ELM is still able to maintain an accuracy that is comparable to the performance of the SVM. A toolbox for the OP-ELM is publicly available online.

  3. [Health risk control for organophosphate pesticides in Mexico: challenges under the Free Trade Treaty].

    PubMed

    Ortega-Ceseña, J; Espinosa-Torres, F; López-Carrillo, L

    1994-01-01

    This paper discusses recent trends concerning the commercialization of pesticides in Mexico and focuses on organophosphates and their potential health risk impact. It points out the existing lack of knowledge on health effects associated to chronic exposure to organophosphate pesticides. A need for both toxicological and epidemiologic studies of chronic exposure is identified. Regulatory programs for pesticides in Mexico and the United States are also compared. The paper also addresses the possibility of effective enforcement of environmental and health regulations in Mexico as a result of more rigorous surveillance under NAFTA.

  4. Plant-parasitic Nematode Acetylcholinesterase Inhibition by Carbamate and Organophosphate Nematicides.

    PubMed

    Opperman, C H; Chang, S

    1990-10-01

    The sensitivity of acetylcholinesterases (ACHE) isolated from the plant-parasitic nematodes Meloidogyne arenaria, M. incognita, and Heterodera glycines and the free-living nematode Caenorhabditis elegans to carbamate and organophosphate nematicides was examined. The AChE from plant-parasitic nematode species were more sensitive to carbamate inhibitors than was AChE from C. elegans, but response to the organophosphates was approximately equivalent. The sulfur-containing phosphate nematicides were poor inhibitors of nematode acetylcholinesterase, but treatment with an oxidizing agent greatly improved inhibition. Behavioral bioassays with living nematodes revealed a poor relationship between enzyme inhibition and expression of symptoms in live nematodes.

  5. Inhalation a significant exposure route for chlorinated organophosphate flame retardants.

    PubMed

    Schreder, Erika D; Uding, Nancy; La Guardia, Mark J

    2016-05-01

    Chlorinated organophosphate flame retardants (ClOPFRs) are widely used as additive flame retardants in consumer products including furniture, children's products, building materials, and textiles. Tests of indoor media in homes, offices, and other environments have shown these compounds are released from products and have become ubiquitous indoor pollutants. In house dust samples from Washington State, U.S.A., ClOPFRs were the flame retardants detected in the highest concentrations. Two ClOPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP or TDCIPP) and tris(2-chloroethyl)phosphate (TCEP), have been designated as carcinogens, and there is growing concern about the toxicity of the homologue tris(1-chloro-2-propyl)phosphate (TCPP or TCIPP). In response to concerns about exposure to these compounds, the European Union and a number of U.S. states have taken regulatory action to restrict their use in certain product categories. To better characterize exposure to ClOPFRs, inhalation exposure was assessed using active personal air samplers in Washington State with both respirable and inhalable particulate fractions collected to assess the likelihood particles penetrate deep into the lungs. Concentrations of ∑ClOPFRs (respirable and inhalable) ranged from 97.1 to 1190 ng m(-3) (mean 426 ng m(-3)), with TCPP detected at the highest concentrations. In general, higher levels were detected in the inhalable particulate fraction. Total intake of ClOPFRs via the inhalation exposure route was estimated to exceed intake via dust ingestion, indicating that inhalation is an important route that should be taken into consideration in assessments of these compounds.

  6. Long-term time series prediction using OP-ELM.

    PubMed

    Grigorievskiy, Alexander; Miche, Yoan; Ventelä, Anne-Mari; Séverin, Eric; Lendasse, Amaury

    2014-03-01

    In this paper, an Optimally Pruned Extreme Learning Machine (OP-ELM) is applied to the problem of long-term time series prediction. Three known strategies for the long-term time series prediction i.e. Recursive, Direct and DirRec are considered in combination with OP-ELM and compared with a baseline linear least squares model and Least-Squares Support Vector Machines (LS-SVM). Among these three strategies DirRec is the most time consuming and its usage with nonlinear models like LS-SVM, where several hyperparameters need to be adjusted, leads to relatively heavy computations. It is shown that OP-ELM, being also a nonlinear model, allows reasonable computational time for the DirRec strategy. In all our experiments, except one, OP-ELM with DirRec strategy outperforms the linear model with any strategy. In contrast to the proposed algorithm, LS-SVM behaves unstably without variable selection. It is also shown that there is no superior strategy for OP-ELM: any of three can be the best. In addition, the prediction accuracy of an ensemble of OP-ELM is studied and it is shown that averaging predictions of the ensemble can improve the accuracy (Mean Square Error) dramatically.

  7. DEVELOPMENT, VALIDATION AND FIELD USE OF NOVEL METHOD FOR EXTRACTING AND ANALYZING ORGANOPHOSPHATE (OP) AND PYRETHROID PESTICIDE METABOLITES AND CREATININE FROM COMMERCIALLY AVAILABLE DISPOSABLE DIAPERS

    EPA Science Inventory

    The ability to efficiently extract urine from disposable diapers ensures an easy to use urine collection protocol and ready compliance for caregivers of very young children. The use of disposable diapers is also desirable because of their high capacity- urine is retained effecti...

  8. 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)
    <...

  9. Bioremediation of pesticide contaminated water using an organophosphate degrading enzyme immobilized on nonwoven polyester textiles.

    PubMed

    Gao, Yuan; Truong, Yen Bach; Cacioli, Paul; Butler, Phil; Kyratzis, Ilias Louis

    2014-01-10

    Bioremediation using enzymes has become an attractive approach for removing hazardous chemicals such as organophosphate pesticides from the environment. Enzymes immobilized on solid carriers are particularly suited for such applications. In this study, the organophosphate degrading enzyme A (OpdA) was covalently immobilized on highly porous nonwoven polyester fabrics for organophosphate pesticide degradation. The fabrics were first activated with ethylenediamine to introduce free amine groups, and the enzyme was then attached using the bifunctional crosslinker glutaraldehyde. The immobilization only slightly increased the Km (for methyl parathion, MP), broadened the pH profile such that the enzyme had significant activity at acidic pH, and enhanced the stability of the enzyme. The OpdA-functionalized fabrics could be stored in a phosphate buffer or in the dry state at 4°C for at least 4 weeks without a large loss of activity. When used in batch mode, the functionalized textiles could degrade 20 μM MP in un-buffered water at liquor to fabric ratios as high as 5000:1 within 2h, and could be used repeatedly. The fabrics could also be made into columns for continuous pesticide degradation. The columns were able to degrade 50 μM MP at high flow rates, and could be used repeatedly over 2 months. These results demonstrate that OpdA immobilized on nonwoven polyester fabrics is useful in environmental remediation of organophosphate compounds.

  10. Acetylcholinesterase of Haematobia irritans (Diptera: Muscidae): Baculovirus expression, biochemical properties and organophosphate insensitivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study reports the baculovirus expression and biochemical characterization of recombinant acetylcholinesterase from Haematobia irritans (L) (rHiAChE) and the effect of the previously described G262A mutation on enzyme activity and sensitivity to selected organophosphates. The rHiAChE was confirm...

  11. Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases

    SciTech Connect

    Androutsopoulos, Vasilis P.; Kanavouras, Konstantinos; Tsatsakis, Aristidis M.

    2011-11-15

    Organophosphate pesticides are a class of compounds that are widely used in agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is involved in the hydrolysis of organophosphate esters. Environmental poisoning by organophosphate compounds has been the main driving force of previous research on PON1 enzymes. Recent discoveries in animal models have revealed the important role of the enzyme in lipid metabolism. However although PON1 function is well established in experimental models, the contribution of PON1 in neurodegenerative diseases remains unclear. In this minireview we summarize the involvement of PON1 genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. A brief overview of latest epidemiological studies, regarding the two most important PON1 coding region polymorphisms PON1-L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with disease occurrence are reported. Notably the MM and RR alleles contribute a risk enhancing effect for the development of some neurodegenerative diseases, which may be explained by the reduced lipoprotein free radical scavenging activity that may give rise to neuronal damage, through distinct mechanism. Conflicting findings that fail to support this postulate may represent the human population ethnic heterogeneity, different sample size and environmental parameters affecting PON1 status. We conclude that further epidemiological studies are required in order to address the exact contribution of PON1 genome in combination with organophosphate exposure in populations with neurodegenerative diseases.

  12. Pyrethroid and DDT Resistance and Organophosphate Susceptibility among Anopheles spp. Mosquitoes, Western Kenya.

    PubMed

    Wanjala, Christine L; Mbugi, Jernard P; Ototo, Edna; Gesuge, Maxwell; Afrane, Yaw A; Atieli, Harrysone E; Zhou, Guofa; Githeko, Andrew K; Yan, Guiyun

    2015-12-01

    We conducted standard insecticide susceptibility testing across western Kenya and found that the Anopheles gambiae mosquito has acquired high resistance to pyrethroids and DDT, patchy resistance to carbamates, but no resistance to organophosphates. Use of non-pyrethroid-based vector control tools may be preferable for malaria prevention in this region.

  13. Pyrethroid and DDT Resistance and Organophosphate Susceptibility among Anopheles spp. Mosquitoes, Western Kenya

    PubMed Central

    Wanjala, Christine L.; Mbugi, Jernard P.; Ototo, Edna; Gesuge, Maxwell; Afrane, Yaw A.; Atieli, Harrysone E.; Zhou, Guofa; Githeko, Andrew K.

    2015-01-01

    We conducted standard insecticide susceptibility testing across western Kenya and found that the Anopheles gambiae mosquito has acquired high resistance to pyrethroids and DDT, patchy resistance to carbamates, but no resistance to organophosphates. Use of non–pyrethroid-based vector control tools may be preferable for malaria prevention in this region. PMID:26583525

  14. 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....

  15. 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....

  16. Cases of poisoning with organophosphates treated at the University Clinical Centre of Kosova.

    PubMed

    Gashi, Musli; Gashi, Sanije; Berisha, Merita; Mekaj, Agon; Gashi, Goneta

    2010-01-01

    Everywhere today, poisonings present a significant and continuous increase of incidence in illness. Poisonings with organophosphates are more and more often. We do not have accurate statistics for this problem. The aim of this work was to present the clinical characteristics of poisoning with organophosphates, treated in University Clinical Centre in Prishtina. With the retrospective method, 23 patients were analyzed, 18 female and 5 male. Out of these, to (43.5%) have had tentative suicide, while 13 (56%) were accidentally exposed to poison. Poisoning with organophosphates was present in 3.8% of the overall number of poisonings. Organophosphate that was found in the analyzed poisoned patients was malathion (known here as Etiol). Average hospitalization time was 8.8 days (1 - 50 days range), average age of the patients was 27.1 years. Mortality scale was 52.1%. All these patients were treated with atropine. Atropine was given in intravenous way during 4.2 +/- 3.5 days and the average total dose was 82 +/- 61.5 mg. Pralidoxime antidote was not given to any of the patients. In adults, the poisoning was done mainly with the aim of suicide. Poisoned children with Etiol are in larger numbers from rural areas.

  17. Role of paraoxonase 1 (PON1) in organophosphate metabolism: implications in neurodegenerative diseases.

    PubMed

    Androutsopoulos, Vasilis P; Kanavouras, Konstantinos; Tsatsakis, Aristidis M

    2011-11-01

    Organophosphate pesticides are a class of compounds that are widely used in agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is involved in the hydrolysis of organophosphate esters. Environmental poisoning by organophosphate compounds has been the main driving force of previous research on PON1 enzymes. Recent discoveries in animal models have revealed the important role of the enzyme in lipid metabolism. However although PON1 function is well established in experimental models, the contribution of PON1 in neurodegenerative diseases remains unclear. In this minireview we summarize the involvement of PON1 genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. A brief overview of latest epidemiological studies, regarding the two most important PON1 coding region polymorphisms PON1-L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with disease occurrence are reported. Notably the MM and RR alleles contribute a risk enhancing effect for the development of some neurodegenerative diseases, which may be explained by the reduced lipoprotein free radical scavenging activity that may give rise to neuronal damage, through distinct mechanism. Conflicting findings that fail to support this postulate may represent the human population ethnic heterogeneity, different sample size and environmental parameters affecting PON1 status. We conclude that further epidemiological studies are required in order to address the exact contribution of PON1 genome in combination with organophosphate exposure in populations with neurodegenerative diseases.

  18. Draft Genome Sequence of Organophosphate-Degrading Ochrobactrum anthropi FRAF13

    PubMed Central

    Damania, Ashish

    2016-01-01

    Ochrobactrum anthropi FRAF13 was isolated from farmland soil in Jersey Village, Texas. FRAF13 is a bacterial microorganism with broad antibiotic resistance that possesses a number of metal-dependent β-lactam enzymes with secondary phosphotriesterase activity that can initiate the breakdown of organophosphate compounds. PMID:27103720

  19. Mechanistic Studies Investigating the Role of Organophosphate Insecticide Exposure in the Development and Exacerbation of Asthma

    DTIC Science & Technology

    2005-04-01

    bronchoconstriction by parathion and mechanism underlying this effect is not known. 172 LEIN AND FRYER 4 airway hyperreactivity including antigen...to organophosphates to airway hyperreactivity and asthma. However, the mechanisms by which these insecticides cause changes in airway function remain...receptors causing contraction of airway smooth muscle resulting in bronchoconstriction . Vagally induced bronchoconstriction is limited by autoinhibitory M2

  20. Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium.

    PubMed

    Calas, André-Guilhem; Perche, Olivier; Richard, Olivier; Perche, Astrid; Pâris, Arnaud; Lauga, Fabien; Herzine, Ameziane; Palomo, Jennifer; Ardourel, Marie-Yvonne; Menuet, Arnaud; Mortaud, Stéphane; Pichon, Jacques; Montécot-Dubourg, Céline

    2016-05-04

    Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.

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

    SciTech Connect

    Lacasana, Marina; Lopez-Flores, Inmaculada; Rodriguez-Barranco, Miguel; Aguilar-Garduno, Clemente; Blanco-Munoz, Julia; Perez-Mendez, Oscar; Gamboa, Ricardo; Bassol, Susana; Cebrian, Mariano E.

    2010-02-15

    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, 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.

  2. Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood

    PubMed Central

    Wetmur, James; Chen, Jia; Zhu, Chenbo; Barr, Dana Boyd; Canfield, Richard L.; Wolff, Mary S.

    2011-01-01

    Background: Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates. Objective: We examined the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months and 6–9 years. Methods: The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urine samples were collected and analyzed for organophosphate metabolites (n = 360). Prenatal maternal blood was analyzed for PON1 activity and genotype. Children returned for neurodevelopment assessments ages 12 months (n = 200), 24 months (n = 276), and 6–9 (n = 169) years of age. Results: Prenatal total dialkylphosphate metabolite level was associated with a decrement in mental development at 12 months among blacks and Hispanics. These associations appeared to be enhanced among children of mothers who carried the PON1 Q192R QR/RR genotype. In later childhood, increasing prenatal total dialkyl- and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon, with a monotonic trend consistent with greater decrements with increasing prenatal exposure. Conclusion: Our findings suggest that prenatal exposure to organophosphates is negatively associated with cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood. PON1 may be an important susceptibility factor for these deleterious effects. PMID:21507778

  3. Intranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning.

    PubMed

    Krishnan, Jishnu K S; Arun, Peethambaran; Appu, Abhilash P; Vijayakumar, Nivetha; Figueiredo, Taíza H; Braga, Maria F M; Baskota, Sudikshya; Olsen, Cara H; Farkas, Natalia; Dagata, John; Frey, William H; Moffett, John R; Namboodiri, Aryan M A

    2016-03-01

    Intranasal delivery is an emerging method for bypassing the blood brain barrier (BBB) and targeting therapeutics to the CNS. Oximes are used to counteract the effects of organophosphate poisoning, but they do not readily cross the BBB. Therefore, they cannot effectively counteract the central neuropathologies caused by cholinergic over-activation when administered peripherally. For these reasons we examined intranasal administration of oximes in an animal model of severe organophosphate poisoning to determine their effectiveness in reducing mortality and seizure-induced neuronal degeneration. Using the paraoxon model of organophosphate poisoning, we administered the standard treatment (intramuscular pralidoxime plus atropine sulphate) to all animals and then compared the effectiveness of intranasal application of obidoxime (OBD) to saline in the control groups. Intranasally administered OBD was effective in partially reducing paraoxon-induced acetylcholinesterase inhibition in the brain and substantially reduced seizure severity and duration. Further, intranasal OBD completely prevented mortality, which was 41% in the animals given standard treatment plus intranasal saline. Fluoro-Jade-B staining revealed extensive neuronal degeneration in the surviving saline-treated animals 24h after paraoxon administration, whereas no detectable degenerating neurons were observed in any of the animals given intranasal OBD 30min before or 5min after paraoxon administration. These findings demonstrate that intranasally administered oximes bypass the BBB more effectively than those administered peripherally and provide an effective method for protecting the brain from organophosphates. The addition of intranasally administered oximes to the current treatment regimen for organophosphate poisoning would improve efficacy, reducing both brain damage and mortality.

  4. 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.

  5. 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.

  6. 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

  7. The MetOp satellite - Weather information from polar orbit

    NASA Astrophysics Data System (ADS)

    Edwards, Peter G.; Berutti, Bruno; Blythe, Paul; Callies, Joerg; Carlier, Stefane; Fransen, Cees; Krutsch, Rainer; Lefebvre, Alain-Robert; Loiselet, Marc; Stricker, Nico

    2006-08-01

    MetOp-A is Europe's first polar-orbiting satellite dedicated to operational meteorology. With its array of advanced instruments, it will provide data of unprecedented accuracy and resolution on temperature and humidity, wind speed and direction over the ocean, and ozone and other trace gases, making a huge contribution to global weather forecasting and climate monitoring. In addition, MetOp-A will observe land and ocean surfaces and its search-and-rescue service will help ships and aircraft in distress.

  8. Quantitative trait locus mapping and functional genomics of an organophosphate resistance trait in the western corn rootworm, Diabrotica virgifera virgifera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  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

    SciTech Connect

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

    2011-11-15

    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 {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 played

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

    SciTech Connect

    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*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.

  11. Organophosphate antidote auto-injectors vs. traditional administration: a time motion study.

    PubMed

    Rebmann, Terri; Clements, Bruce W; Bailey, Jeffrey A; Evans, R Gregory

    2009-08-01

    Organophosphates may be used as weapons in chemical attacks on civilian or military populations. Antidotes are available to counter the effects of organophosphates, but they must be administered shortly after exposure. Timing required to administer organophosphate antidotes using traditional equipment vs. auto-injectors has not been studied. This study is intended to quantify and compare the time required to administer organophosphate antidotes using traditional equipment vs. auto-injectors in different treatment conditions. The study was a randomized, un-blinded design. There were 62 participants assigned to one of three groups: Mark I, ATNAA (antidote treatment nerve agent auto-injector), and traditional needle/syringe; however, the results from only 56 participants could be analyzed. Injection trials were videotaped. Subjects also completed a 14-item survey containing demographic questions, perceived ease of injection, receipt of prior training, and preferred training format for organophosphate treatment. Injection time differentials were compared using one-way analysis of variance; post hoc evaluation was performed using the Scheffe test with Bonferroni correction. Fifty-six subjects completed this study. The ATNAA required less time to administer than the Mark I or traditional needle/syringe devices (p < .001). There was no difference in time to administer the Mark I auto-injectors vs. a traditional needle/syringe. There were no differences between injection time and occupation, receipt of prior training, wearing of personal protective equipment, or perceived ease of injection device use. The use of auto-injectors shortens response time for administering organophosphate antidote treatment. An ATNAA auto-injector can be administered in less than half the time it takes to administer a single injection using a needle and syringe or two injections using a Mark I. Mark I can be administered in approximately the same amount of time it takes to administer a single

  12. Fluorescence Spectroscopy Approaches for the Development of a Real-Time Organophosphate Detection System Using an Enzymatic Sensor

    PubMed Central

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

    2015-01-01

    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. PMID:25671511

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. ProOpDB: Prokaryotic Operon DataBase.

    PubMed

    Taboada, Blanca; Ciria, Ricardo; Martinez-Guerrero, Cristian E; Merino, Enrique

    2012-01-01

    The Prokaryotic Operon DataBase (ProOpDB, http://operons.ibt.unam.mx/OperonPredictor) constitutes one of the most precise and complete repositories of operon predictions now available. Using our novel and highly accurate operon identification algorithm, we have predicted the operon structures of more than 1200 prokaryotic genomes. ProOpDB offers diverse alternatives by which a set of operon predictions can be retrieved including: (i) organism name, (ii) metabolic pathways, as defined by the KEGG database, (iii) gene orthology, as defined by the COG database, (iv) conserved protein domains, as defined by the Pfam database, (v) reference gene and (vi) reference operon, among others. In order to limit the operon output to non-redundant organisms, ProOpDB offers an efficient method to select the most representative organisms based on a precompiled phylogenetic distances matrix. In addition, the ProOpDB operon predictions are used directly as the input data of our Gene Context Tool to visualize their genomic context and retrieve the sequence of their corresponding 5' regulatory regions, as well as the nucleotide or amino acid sequences of their genes.

  15. 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…

  16. Engaging the public through writing an op-ed

    NASA Astrophysics Data System (ADS)

    Labosier, Chris; Zhu, Laiyin; Quiring, Steven

    2012-10-01

    In May, prior to the start of the 2012 hurricane season, AGU asked us to write an op-ed for the Houston Chronicle on the importance of funding hurricane research. We were excited to be asked and pleased that AGU facilitated the process by providing us with some guidance on writing the op-ed. Given the impact that Hurricane Ike had in Texas just a few years ago, we felt it was important to remind the citizens of the greater Houston metropolitan area of the societal benefits of funding hurricane research. Thanks to the assistance of AGU staff, writing the article required only a few hours of time. Our op-ed was published in the print edition of the Houston Chronicle on 1 June 2012, the official start of the hurricane season (http://www.chron.com/default/article/Tight-budgets-posing-threat-to-Texas-hurricane-3600363.php). It was picked up by the media relations office in the College of Geosciences at Texas A&M University and featured on the college's Web site in the dean's biweekly briefing and on its Facebook page. As a result, the op-ed reached a large and diverse audience.

  17. Theoretical Prerequisites for the Possible Use of Bacteria which Split Organophosphates in Order to Increase the Yield of Nutrient Yeast and its Nitrogen and Phosphorous Content,

    DTIC Science & Technology

    1985-10-28

    FOR THE POSSIBLE USE OF BACTERIA WHICH SPLIT ORGANOPHOSPHATES IN ORDER TO INCREASE THE YIELD OF NUTRIENT YEAST AND ITS NITROGEN:AND PHOSPHOROUS CONTENT...ORGANOPHOSPHATES IN ORDER TO IN- -SI CfA &I CREASE THE YIELD OF NUTRIENT YEAST AND ITS NITROGEN DTCTAB AND PHOSPHOROUS CONTENT -F unec By: D.L. Shamis English...POSSIBLE USE OF BACTERIA WHICH SPLIT ORGANOPHOSPHATES IN ORDER TO INCREASE THE YIELD OF NUTRIENT YEAST AND ITS NITROGEN AND PHOSPHOROUS CONTENT D. L. Shamis

  18. Microplate assay analysis of the distribution of organophosphate and carbamate resistance in Guatemalan Anopheles albimanus

    PubMed Central

    Brogdon, W. G.; Beach, R. F.; Stewart, J. M.; Castanaza, L.

    1988-01-01

    Simple microplate assay methods for determining the frequency of insecticide resistance in single mosquitos were used to study the distribution and localization of organophosphate and carbamate resistance in field populations of Anopheles albimanus Weidemann in Guatemala, where such resistance, caused by heavy use of agricultural pesticides, has long been assumed to be widespread. Areas of complete susceptibility to organophosphates and carbamates were observed, as well as areas where the resistant phenotypes represented up to 98% of the population. Overall, the resistance levels were lower and more localized than expected. Two mechanisms of resistance were identified by the microassay methods. These were the elevated esterase (nonspecific esterase) and insensitive acetylcholinesterase mechanisms which were selected independently, the former (documented for the first time in Central American anophelines) being predominant. These methods represent a promising new technology for the detection and assessment of resistance and will facilitate improved control strategy decisions. PMID:3262440

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

    SciTech Connect

    Lacasana, Marina; Lopez-Flores, Inmaculada; Rodriguez-Barranco, Miguel; Aguilar-Garduno, Clemente; Blanco-Munoz, Julia; Perez-Mendez, Oscar; Gamboa, Ricardo; Gonzalez-Alzaga, Beatriz; Bassol, Susana; Cebrian, Mariano E.

    2010-11-15

    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, during 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.

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

    DTIC Science & Technology

    2005-05-01

    detailed kinetics on the rates of inactivation by cycloheptyl, isopropyl and 3,3-dimethylbutyl methylphosphonyl thioesters and the reactivation of the...enzymes. This assay has enabled us to measure the pH dependence and the catalytic parameters of oxime- assisted organophosphate hydrolysis. The kinetics ... malathion , metrifonate, methylparathion-oxon, DDVP) and those that have a diethoxy or larger moiety (paraoxon, diisopropylfluorphosphate). The Sp

  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

    2016-08-24

    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.Journal of Exposure Science

  2. A Study of Initial Employment Characteristics between Co-op and Non-co-op Community College Graduates.

    ERIC Educational Resources Information Center

    Owen, J. Robert; Clark, Aaron C.

    2001-01-01

    Comparison of 24 community college engineering graduates who participated in cooperative education and 13 nonco-op graduates found no significant employment differences in terms of organizational socialization, relevance of job-to-career plans, access to resources, or participation in decision making. Findings may be specific to this community…

  3. New Onset Refractory Status Epilepticus as an Unusual Presentation of a Suspected Organophosphate Poisoning

    PubMed Central

    Waheed, Shahan; Sabeen, Amber; Ullah Khan, Nadeem

    2014-01-01

    New onset refractory status epilepticus (NORSE) is a new entity in medical literature. It has different infectious and noninfectious etiologies showing a devastating impact onto the clinical outcome of patients. Therapy with anaesthetic and antiepileptic agents often fails to improve the condition, unless the primary cause is rectified. Here is presented the case of a young female with a history of depression who after a recent bereavement came to the Emergency Department of Aga Khan University Hospital with complaints of drowsiness that lasted for few hours. Though she had no history of organophosphate poisoning, her physical examination and further investigations were suggestive of the diagnosis. During her hospital stay, she developed refractory status epilepticus. Her seizures did not respond to standard antiepileptic and intravenous anesthetic agents and subsided only after intravenous infusion of atropine for a few days. Organophosphate poisoning is a very common presentation in the developing world and the associated status epilepticus poses a devastating problem for emergency physicians. In patients with suspected organophosphate poisoning with favoring clinical exam findings, the continuation of atropine intravenous infusion can be a safe option to abate seizures. PMID:25580311

  4. Colorimetric dipstick for assay of organophosphate pesticides and nerve agents represented by paraoxon, sarin and VX.

    PubMed

    Pohanka, Miroslav; Karasova, Jana Zdarova; Kuca, Kamil; Pikula, Jiri; Holas, Ondrej; Korabecny, Jan; Cabal, Jiri

    2010-04-15

    A dipstick for fast assay of nerve agents and organophosphate pesticides was developed. Indicator pH papers were used as detectors. The principle of the assay is based on enzymatic hydrolysis of acetylcholine into acetic acid and choline by acetylcholinesterase. Acidification of the reaction medium due to accumulation of acetic acid was visible. The colour changed from dark red to yellow as the pH indicator recognized pH shift. Presence of an organophosphate pesticide or a nerve agent results in irreversible inhibition of acetylcholinesterase intercepted on the dipstick. The inhibition stops the enzymatic reaction. The inhibition appears as no change of the medium pH. Three compounds were assayed: paraoxon-ethyl as representative organophosphate pesticides and nerve agents sarin and VX. The achieved limit of detection was 5 x 10(-8)M for paraoxon-ethyl and 5 x 10(-9)M for sarin and VX. Dipsticks were found stable for at least one month. Suitability of these dipsticks for routine assay is discussed.

  5. 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.

  6. Exposure of male mice to two kinds of organophosphate flame retardants (OPFRs) induced oxidative stress and endocrine disruption.

    PubMed

    Chen, Guanliang; Jin, Yuanxiang; Wu, Yan; Liu, Ling; Fu, Zhengwei

    2015-07-01

    Triphenyl phosphate (TPP) and tris(2-chloroethyl) phosphate (TCEP) are two of the most common organophosphate flame retardants in the ecosystem. Effects of TPP and TCEP on the induction of oxidative stress and endocrine disruption were evaluated in five weeks old male mice. After receiving 100, 300 mg/kg/bodyweight oral exposure to TPP and TCEP for 35 days, the body and testis weights decreased in 300 mg/kg TPP and TCEP treated groups. Hepatic malondialdehyde (MDA) contents increased significantly in both TPP treated groups, while the contents of glutathione (GSH) decreased significantly in 300 mg/kg TPP and both TCEP treated groups. In addition, the hepatic activities of antioxidant enzymes including glutathione peroxidase (GPX), catalase (CAT) and glutathione S-transferase (GST) as well as their related gene expression were affected by TPP or TECP exposure. On the other hand, 300 mg/kg of TPP or TECP treatment resulted in histopathological damage and the decrease of testicular testosterone levels. Moreover, the expression of main genes related to testosterone synthesis including steroidogenic acute regulatory protein (StAR), low-density lipoprotein receptor (LDL-R), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α) in the testes also decreased after the exposure to 300 mg/kg TPP or TCEP for 35 days. Combined with the effects on physiology, histopathology and the expression of genes, TPP and TCEP can induce oxidative stress and endocrine disruption in mice.

  7. Organophosphate Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

    DTIC Science & Technology

    2015-10-01

    a third scan after a 4 week (OP-free) washout period. For each animal, a separate 6 hour and 24 hour scan was performed after Mn2+ eye injection...third scan was performed after a 4 week (OP-free) washout period (after the third and final Mg2+ eye injection) in each animal. 5. For each animal a...performed on the day following the last drug injection (after another Mg2+ eye injection) in each animal. 4. A third scan was performed after a 4 week (OP

  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. 7 CFR 1944.662 - Eligibility of HPG assistance on rental properties or co-ops.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... co-ops. 1944.662 Section 1944.662 Agriculture Regulations of the Department of Agriculture (Continued... Preservation Grants § 1944.662 Eligibility of HPG assistance on rental properties or co-ops. (a) Ownership. The owner(s) of rental properties or co-ops must own the dwelling at the time of receiving assistance...

  10. 7 CFR 1944.662 - Eligibility of HPG assistance on rental properties or co-ops.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... co-ops. 1944.662 Section 1944.662 Agriculture Regulations of the Department of Agriculture (Continued... Preservation Grants § 1944.662 Eligibility of HPG assistance on rental properties or co-ops. (a) Ownership. The owner(s) of rental properties or co-ops must own the dwelling at the time of receiving assistance...

  11. 7 CFR 1944.662 - Eligibility of HPG assistance on rental properties or co-ops.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... co-ops. 1944.662 Section 1944.662 Agriculture Regulations of the Department of Agriculture (Continued... Preservation Grants § 1944.662 Eligibility of HPG assistance on rental properties or co-ops. (a) Ownership. The owner(s) of rental properties or co-ops must own the dwelling at the time of receiving assistance...

  12. 7 CFR 1944.662 - Eligibility of HPG assistance on rental properties or co-ops.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... co-ops. 1944.662 Section 1944.662 Agriculture Regulations of the Department of Agriculture (Continued... Preservation Grants § 1944.662 Eligibility of HPG assistance on rental properties or co-ops. (a) Ownership. The owner(s) of rental properties or co-ops must own the dwelling at the time of receiving assistance...

  13. 7 CFR 1944.662 - Eligibility of HPG assistance on rental properties or co-ops.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... co-ops. 1944.662 Section 1944.662 Agriculture Regulations of the Department of Agriculture (Continued... Preservation Grants § 1944.662 Eligibility of HPG assistance on rental properties or co-ops. (a) Ownership. The owner(s) of rental properties or co-ops must own the dwelling at the time of receiving assistance...

  14. A 10-minute point-of-care assay for detection of blood protein adducts resulting from low level exposure to organophosphate nerve agents.

    PubMed

    VanDine, Robert; Babu, Uma Mahesh; Condon, Peter; Mendez, Arlene; Sambursky, Robert

    2013-03-25

    The OrganoTox test is a rapid, point-of-care assay capable of detecting clinically relevant organophosphate (OP) poisoning after low-level exposure to sarin, soman, tabun, or VX chemical nerve agents. The test utilizes either a finger stick peripheral blood sample or plasma specimen. While high-level nerve agent exposure can quickly lead to death, low-level exposure produces vague, nondescript signs and symptoms that are not easily clinically differentiated from other conditions. In initial testing, the OrganoTox test was used to detect the presence of blood protein-nerve agent adducts in exposed blood samples. In order to mimic the in vivo exposure as closely as possible, nerve agents stored in organic solvents were spiked in minute quantities into whole blood samples. For performance testing, 40 plasma samples were spiked with sarin, soman, tabun, or VX and 10 normal plasma samples were used as the negative control. The 40 nerve agent-spiked plasma samples included 10 replicates of each agent. At the clinically relevant low-level exposure of 10 ng/ml, the OrganoTox test demonstrated 100% sensitivity for soman, tabun, and VX and 80% sensitivity for sarin. The OrganoTox test demonstrated greater than 97% specificity with 150 blood samples obtained from healthy adults. No cross-reactivity or interference from pesticide precursor compounds was found. A rapid test for nerve agent exposure will help identify affected patients earlier in the clinical course and trigger more appropriate medical management in a more timely manner.

  15. Work-Op IV summary: lessons from iron opacities

    SciTech Connect

    Davidson, S J; Iglesias, C A; Minguez, E; Serduke, F J D

    1999-04-16

    The fourth international LTE opacity workshop and code comparison study, WorkOp-IV, was held in Madrid in 1997. Results of this workshop are summarized with a focus on iron opacities. In particular, the astrophysically important photon absorption region between 50 and 80 eV is emphasized for a sequence of iron plasmas at densities and temperatures that produce nearly the same average ionization stage (Z* {approximately} 8.6). Experimental data that addressed this spectral region is also reviewed.

  16. Optoelectronic Device Integration in Silicon (OpSIS)

    DTIC Science & Technology

    2015-10-26

    the community as part of the OpSIS-IME MPW service. © (2013) COPYRIGHT Society of Photo -Optical Instrumentation Engineers (SPIE). Downloading of the...germanium direct contact” Vol.22, No.9; 11367-11375 (2013). (9 Google Scholar Citations) Abstract: We report a Ge-on-Si photodetector without doped Ge or...versus optical signal-to-noise ratio. 27 Fig. 1 WDM ring transmitter. (a) Architecture diagram. (b) Chip photo . 28. Ding, Ran; Liu, Yang; Li, Qi

  17. All Conservation Opportunity Areas (ECO.RES.ALL_OP_AREAS)

    EPA Pesticide Factsheets

    The All_OP_Areas GIS layer are all the Conservation Opportunity Areas identified by MoRAP (produced for EPA Region 7). They designate areas with potential for forest, grassland and forest/grassland mosaic conservation. These are areas of natural or semi-natural forest land cover that are at least 75 meters away from roads and away from patch edges. OAs were modeled by creating distance grids using the National Land Cover Database and the Census Bureau's TIGER roads files.

  18. 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.

  19. PARAOXONASE 1 (PON1) AS A GENETIC DETERMINANT OF SUSCEPTIBILITY TO ORGANOPHOSPHATE TOXICITY

    PubMed Central

    Costa, Lucio G.; Giordano, Gennaro; Cole, Toby B.; Marsillach, Judit; Furlong, Clement E.

    2012-01-01

    Paraoxonase (PON1) is an A-esterase capable of hydrolyzing the active metabolites (oxons) of a number of organophosphorus (OP) insecticides such as parathion, diazinon and chlorpyrifos. PON1 activity is highest in liver and in plasma. Human PON1 displays two polymorphisms in the coding region (Q192R and L55M) and several polymorphisms in the promoter and the 3’-UTR regions. The Q192R polymorphism imparts differential catalytic activity toward some OP substrates, while the polymorphism at position –108 (C/T) is the major contributor of differences in the levels of PON1 expression. Both contribute to determining an individual's PON1 “status”. Animal studies have shown that PON1 is an important determinant of OP toxicity. Administration of exogenous PON1 to rats or mice protects them from the toxicity of specific OPs. PON1 knockout mice display a high sensitivity to the toxicity of diazoxon and chlorpyrifos oxon, but not of paraoxon. In vitro catalytic efficiencies of purified PON192 alloforms for hydrolysis of specific oxon substrates accurately predict the degree of in vivo protection afforded by each isoform. Evidence is slowly emerging that a low PON1 status may increase susceptibility to OP toxicity in humans. Low PON1 activity may also contribute to the developmental toxicity and neurotoxicity of OPs, as shown by animal and human studies. PMID:22884923

  20. Influence of organophosphate poisoning on human dendritic cells.

    PubMed

    Schäfer, Marina; Koppe, Franziska; Stenger, Bernhard; Brochhausen, Christoph; Schmidt, Annette; Steinritz, Dirk; Thiermann, Horst; Kirkpatrick, Charles James; Pohl, Christine

    2013-12-05

    Organophosphourus compounds (OPC, including nerve agents and pesticides) exhibit acute toxicity by inhibition of acetylcholinesterase. Lung affections are frequent complications and a risk factor for death. In addition, epidemiological studies reported immunological alterations after OPC exposure. In our experiments we investigated the effects of organophosphourus pesticides dimethoate and chlorpyrifos on dendritic cells (DC) that are essential for the initial immune response, especially in the pulmonary system. DC, differentiated from the monocyte cell line THP-1 by using various cytokines (IL-4, GM-CSF, TNF-α, Ionomycin), were exposed to organophosphourus compounds at different concentrations for a 24h time period. DC were characterized by flow cytometry and immunofluorescence using typical dendritic cell markers (e.g., CD11c, CD209 and CD83). After OPC exposure we investigated cell death, the secretion profile of inflammatory mediators, changes of DC morphology, and the effect on protein kinase signalling pathways. Our results revealed a successful differentiation of THP-1 into DC. OPC exposure caused a significant concentration-dependent influence on DC: Dendrites of the DC were shortened and damaged, DC-specific cell surface markers (i.e., CD83and CD209) decreased dramatically after chlorpyrifos exposure. Interestingly, the effects caused by dimethoate were in general less pronounced. The organophosphourus compounds affected the release of inflammatory cytokines, such as IL-1ß and IL-8. The anti-inflammatory cytokine IL-10 was significantly down regulated. Protein kinases like the Akt family or ERK, which are essential for cell survival and proliferation, were inhibited by both OPC. These findings indicate that the tested organophosphourus compounds induced significant changes in cell morphology, inhibited anti-inflammatory cytokines and influenced important protein signalling pathways which are involved in regulation of apoptosis. Thus our results highlight

  1. Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

    SciTech Connect

    Halbrook, R.S.; Shugart, L.R.; Watson, A.P.; Munro, N.B.; Linnabary, R.D. )

    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. A 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.

  2. Mechanism of organophosphates (nerve gases and pesticides) and antidotes: electron transfer and oxidative stress.

    PubMed

    Kovacic, Peter

    2003-12-01

    Evidence indicates that nerve gas toxins operate in ways in addition to inhibition of acetylcholine esterase. Alternative bioactivities are discussed with focus on electron transfer. The main class, including pralidoxime (2-PAM), incorporates conjugated iminium and oxime moieties that are electron affinic. Various physiological properties of iminium and oxime species are reviewed. The organophosphates encompass both nerve gases and insecticides, possessing similar properties, but different activities. Toxic manifestations are apparently due, in part, to oxidative stress. Alkylation of DNA takes place which may lead to generation of reactive oxygen species. Structure-activity relationships are examined, including reduction potentials and the captodative effect.

  3. A fluorescent dipyrrinone oxime for the detection of pesticides and other organophosphates.

    PubMed

    Walton, Ian; Davis, Marauo; Munro, Lyndsay; Catalano, Vincent J; Cragg, Peter J; Huggins, Michael T; Wallace, Karl J

    2012-06-01

    An N,N-carbonyl-bridged dipyrrinone oxime has been synthesized and studied as a potential sensor for organophosphates. The molecular sensor underwent a drastic colorimetric response upon formation of the adduct. The pesticide dimethoate was found to produce the biggest spectral response, with a limit of detection equal to 4.0 ppm using UV-visible spectroscopy. Minimal fluorescence "turn on" via a PET mechanism was seen, and molecular modeling studies were used to explain the lower than expected PET response. The X-ray crystal structure of the fluorescent dipyrrinone oxime was also obtained.

  4. 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

  5. The effect of extracellular polysaccharides on the goethite-surface promoted hydrolysis of organophosphates.

    NASA Astrophysics Data System (ADS)

    Kenney, J. P. L.; Olsson, R.; Giesler, R.; Persson, P.

    2012-04-01

    Organophosphate monoesters comprise a significant fraction of phosphate in soils. In order to access phosphorus needed for growth, plants and microorganisms often require the hydrolysis of large organophosphate molecules. This hydrolysis can be enzymatic or a reaction promoted by contact with an environmental surface. Because phosphorus strongly adsorbs to environmental particles, the fate and transport of phosphorus in the biosphere can be significantly impacted by reactions at the surfaces of these particles. Soil minerals, including the common Fe(III) mineral goethite, have been shown to increase the rate of hydrolysis of organophosphates by acting as catalysts. Many enzyme-secreting microbes and plants can also release extracellular polysaccharides (EPS) into their local environments. EPS is known to adsorb to environmental particles, including goethite. The adsorption of EPS may alter the physico-chemistry of the mineral-phosphate-enzyme system by impacting either the adsorption or enzymatic hydrolysis of organophosphate. Currently, there is little information available regarding the ability of EPS to enhance or inhibit the availability of essential nutrients, such as phosphate, in the environment. In this study we have investigated the hydrolysis of the phosphate monoesters, glucose phosphate (GP) and p-nitrophenyl phosphate (pNPP). To investigate the hydrolysis mechanisms and extent of hydrolysis of phosphate monoesters we studied three systems: 1) abiotic hydrolysis, where monoesters are adsorbed on goethite surfaces; 2) enzymatic hydrolysis where the monoesters are adsorbed to goethite then exposed to an enzyme; and 3) testing whether the presence of alginate, which is used as a model for EPS, can inhibit or enhance the abiotic or enzymatic hydrolysis. To investigate this we used infrared spectroscopy and the ATR sampling technique. Abiotic hydrolysis was examined using goethite as the environmental surface. Adsorption of each monoester to the goethite was

  6. 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 saltwater had lost more weight and had higher plasma Na and uric acid concentrations 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.

  7. Toxicological studies of organophosphate and pyrethroid insecticides for controlling the fruit fly Dacus ciliatus (Diptera: Tephritidae).

    PubMed

    Maklakov, A; Ishaaya, I; Freidberg, A; Yawetz, A; Horowitz, A R; Yarom, I

    2001-10-01

    The fruit fly Dacus ciliatus Loew is a pest of the fruits of many cucurbit species. We studied the effect of organaophosphate and pyrethroid compounds on the adult flies by using surface contact and oral administration. In contrast to other fruit flies, we found that organophosphates were ineffective against D. ciliatus. This was supported by the insignificant decrease of head acetylcholinesterase activity. All tested pyrethroids showed satisfactory killing ability, rapid and massive knockdown effect, and prevention of oviposition. Piperonyl butoxide considerably increased the toxicity of pyrethroids, which can be explained by oxidase detoxification of these compounds in D. ciliatus. It can be concluded that pyrethroids have high potential for controlling D. ciliatus.

  8. Cholinesterase Structure: Identification of Residues and Domains Affecting Organophosphate Inhibition and Catalysis

    DTIC Science & Technology

    1998-04-01

    phosphatase with a capacity to turn over the organophosphate as a hydrolytic reaction. This has been elegantly accomplished by Broomfield, Lockridge and their...Y., Radid, Z., Tsigelny, I., Vellom, D.C., Pickering, N.A., Quinn, D.M., Doctor, B.P. and Taylor, P. Amino Acid Controlling Reactivation of a Chiral...B.P. Doctor and P. Taylor, Eds.) Plenum Press, N.Y., 15-22 (1995). 14P. Radid, Z., Quinn, D.M. and Vellom, D.C. Amino Acid Residues in

  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.

  10. Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

    SciTech Connect

    Schallreuter, Karin U.; University of Bradford ). E-mail: K.Schallreuter@bradford.ac.uk; Gibbons, Nicholas C.J.; Elwary, Souna M.; Parkin, Susan M.; Wood, John M.

    2007-04-20

    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} surface 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.

  11. Pyrethroid and organophosphate pesticide-associated toxicity in two coastal watersheds (California, USA).

    PubMed

    Phillips, Bryn M; Anderson, Brian S; Hunt, John W; Siegler, Katie; Voorhees, Jennifer P; Tjeerdema, Ron S; McNeill, Katie

    2012-07-01

    Portions of the Santa Maria River and Oso Flaco Creek watersheds in central California, USA, are listed as impaired under section 303(d) of the Clean Water Act and require development of total maximum daily load (TMDL) allocations. These listings are for general pesticide contamination, but are largely based on historic monitoring of sediment and fish tissue samples that showed contamination by organochlorine pesticides. Recent studies have shown that toxicity in these watersheds is caused by organophosphate pesticides (water and sediment) and pyrethroid pesticides (sediment). The present study was designed to provide information on the temporal and spatial variability of toxicity associated with these pesticides to better inform the TMDL process. Ten stations were sampled in four study areas, one with urban influences, and the remaining in agriculture production areas. Water toxicity was assessed with the water flea Ceriodaphnia dubia, and sediment toxicity was assessed with the amphipod Hyalella azteca. Stations in the lower Santa Maria River had the highest incidence of toxicity, followed by stations influenced by urban inputs. Toxicity identification evaluations and chemical analysis demonstrated that the majority of the observed water toxicity was attributed to organophosphate pesticides, particularly chlorpyrifos, and that sediment toxicity was caused by mixtures of pyrethroid pesticides. The results demonstrate that both agriculture and urban land uses are contributing toxic concentrations of these pesticides to adjacent watersheds, and regional water quality regulators are now using this information to develop management objectives.

  12. 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

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

    PubMed

    Julien, Rhona; Adamkiewicz, Gary; Levy, Jonathan I; Bennett, Deborah; Nishioka, Marcia; Spengler, John D

    2008-03-01

    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 apartments and analyzed for eleven pyrethoids (e.g., permethrin and cyfluthrin) and two organophosphates (chlorpyrifos and diazinon) in house dust using GC/MS. Agreement between sampling methods were evaluated using Spearman correlations and Kappa statistics. Permethrin and chlorpyrifos were detected in kitchen floor wipes in all homes, followed in frequency of detects by diazinon (98%), cypermethrin (90%) and cyfluthrin (71%). At least six pesticides were detected in kitchen floor wipes in the majority of the homes (range 3-8). Positive and statistically significant correlations among dust matrices were observed between kitchen floor wipes and living room vacuum dust, including for diazinon (r=0.62) and cyfluthrin (r=0.69). Detection of several pesticides including banned or restricted use products in some public housing units, underscore the need for alternative pest management strategies that embrace the safe and judicious use of pest control products.

  14. 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.

  15. 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

  16. 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

  17. Study of the mechanism of Flavobacterium sp. for hydrolyzing organophosphate pesticides.

    PubMed

    Ortiz-Hernández, M L; Quintero-Ramírez, R; Nava-Ocampo, A A; Bello-Ramírez, A M

    2003-12-01

    The biotransformation by Flavobacterium sp. of the following organophosphate pesticides was experimentally and theoretically studied: phorate, tetrachlorvinphos, methyl-parathion, terbufos, trichloronate, ethoprophos, phosphamidon, fenitrothion, dimethoate and DEF. The Flavobacterium sp. ATCC 27551 strain bearing the organophosphate-degradation gene was used. Bacteria were incubated in the presence of each pesticide for a duration of 7 days. Parent pesticides were identified and quantified by means of a gas-chromatography mass spectrum system. Activity was considered as the amount (micromol) of each pesticide degraded by Flavobacterium sp. Also, structural parameters obtained by means of the CAChe program package for biomolecules, the reactivity index of phosphorus, of oxygen at the P = O function and of sulfur at the P = S function, and lipophilicity (log Poct) (ALOGPS v. 2.0) were obtained for each pesticide. Pesticides were hydrolyzed at the bond between phosphorous and the heteroatom, producing phosphoric acid and three metabolites. Enzymatic activity was significantly explained by the following multiple linear relationship: Enzymatic activity = 162.2 - 9.5(dihedral angle energy) - 25.0(Total energy) - 0.51(Molecular weight). Finally, a mechanism of Flavobacterium sp. to hydrolyze pesticides was proposed.

  18. Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States.

    PubMed

    Hoffman, Kate; Butt, Craig M; Webster, Thomas F; Preston, Emma V; Hammel, Stephanie C; Makey, Colleen; Lorenzo, Amelia M; Cooper, Ellen M; Carignan, Courtney; Meeker, John D; Hauser, Russ; Soubry, Adelheid; Murphy, Susan K; Price, Thomas M; Hoyo, Cathrine; Mendelsohn, Emma; Congleton, Johanna; Daniels, Julie L; Stapleton, Heather M

    2017-03-14

    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 (10(β) = 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.

  19. Ionic liquids composed of phosphonium cations and organophosphate, carboxylate, and sulfonate as lubricant antiwear additives

    SciTech Connect

    Zhou, Yan; Dyck, Jeffrey; Graham, Todd; Luo, Huimin; Leonard, Donovan N.; Qu, Jun

    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 outperformed 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.

  20. 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.

  1. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  2. 14O+p elastic scattering in a microscopic cluster model

    SciTech Connect

    Descouvemont, P.; Baye, D.; Leo, F.

    2006-04-26

    The 14O+p elastic scattering is analyzed in a fully microscopic cluster model. With the Resonating Group Method associated with the microscopic R-matrix theory, phase shifts and cross sections are calculated. Data on 16O+p are used to test the precision of the model. For the 14O+p elastic scattering, an excellent agreement is found with recent experimental data. Resonances properties in 15F are discussed.

  3. 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…

  4. Brain acetylcholinesterase activity recovery following acute methyl parathion intoxication in two feral rodent species: comparison to laboratory rodents

    SciTech Connect

    Roberts, D.K.; Silvey, N.J.; Bailey, E.M. Jr.

    1988-07-01

    Widespread use of organophosphorus insecticides (OPs) has produced both acute and chronic intoxication among nontarget organisms. Most such studies have included fish and birds as opposed to mammals. However, numerous OP toxicity studies have been conducted on laboratory rodents creating a temptation to apply this data to feral rodents. Chronic OP exposure has been reported to produce cholinergic adaptation which in turn lowers mortality rates following a subsequent acute anticholinesterase exposure. The relevance that these laboratory rodent studies have on feral rodents is subject to debate. Field studies involving OP exposure among nontarget feral mammals have produced contradictory results. Increased mortality as a result of repeated OP application has been reported. This observation may be of considerable importance to nontarget feral rodent populations due to the repetitive nature of OP application protocols. The ability of feral rodents to recover brain AChE activity (BAA) between OP application intervals undoubtedly promotes their survival. This study investigated and compared BAA recovery following acute oral methyl parathion intoxication among 2 feral rodent species and among 2 common laboratory rodent species.

  5. Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment.

    PubMed

    Bajgar, Jirí

    2004-01-01

    OP/nerve agents are still considered as important chemicals acting on living organisms and are widely used. They are characterized according to their action as compounds influencing cholinergic nerve transmission via inhibition of AChE. Modeling of this action and extrapolation of experimental data from animals to humans is more possible for highly toxic agents than for the OP. The symptoms of intoxication comprise nicotinic, muscarinic, and central symptoms; for some OP/nerve agents, a delayed neurotoxicity is observed. Cholinesterases (AChE and BuChE) are characterized as the main enzymes involved in the toxic effect of these compounds, including molecular forms. The activity of both enzymes (and molecular forms) is influenced by inhibitors (reversible, irreversible, and allosteric) and other factors, such as pathological states. There are different methods for cholinesterase determination; however, the most frequent is the method based on the hydrolysis of thiocholine esters and subsequent detection of free SH-group of the released thiocholine. The diagnosis of OP/nerve agent poisoning is based on anamnesis, the clinical status of the intoxicated organism, and on cholinesterase determination in the blood. For nerve agent intoxication, AChE in the red blood cell is more diagnostically important than BuChE activity in the plasma. This enzyme is a good diagnostic marker for intoxication with OP pesticides. Some other biochemical examinations are recommended, especially arterial blood gas, blood pH, minerals, and some other specialized parameters usually not available in all clinical laboratories. These special examinations are important for prognosis of the intoxication, for effective treatment, and for retrospective analysis of the agent used for exposure. Some principles of prophylaxis against OP/nerve agent poisoning comprising the administration of reversible cholinesterase inhibitors such as pyridostigmine (alone or in combination with other drugs), scavengers

  6. 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...

  7. 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

  8. 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.

  9. Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient, macrophage-deficient op/op mouse: evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma.

    PubMed

    Nowicki, A; Szenajch, J; Ostrowska, G; Wojtowicz, A; Wojtowicz, K; Kruszewski, A A; Maruszynski, M; Aukerman, S L; Wiktor-Jedrzejczak, W

    1996-01-03

    Macrophages have been suggested to play a major role in the immune response to cancer. They have also been suggested to stimulate the formation of tumor stroma and to promote tumor vascularization. The availability of the op/op mouse, which has no endogenous colony-stimulating factor 1 (CSF-1) and which possesses a profound macrophage deficiency, provides a new model to verify these notions. Subcutaneous growth of transplantable Lewis lung cancer (LLC) is markedly impaired in the op/op mice compared with normal littermates. Treatment of tumor-bearing op/op mice with human recombinant CSF-1 corrects this impairment. Histological analysis of tumors grown in op/op and normal mice revealed marked differences. Tumors grown in op/op mice display a decreased mitotic index and pronounced necrosis, particularly hemorrhagic. Moreover, particularly in the op/op tumors, peculiar sinusoid-like abortive vessels (not filled with blood) have been observed. These tumors, in contrast to tumors grown in normal mice, are almost deprived of regular arteries and veins. In contrast to tumors grown in normal mice, they exhibit almost no Sirius red-stained collagenous fibers and Gomori silver-stained reticular fibers. Our data suggest that the CSF-1-dependent macrophage subpopulation missing in op/op mice plays a primary role in supporting tumor stroma formation and tumor vascularization in murine LLC tumors.

  10. Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population.

    PubMed

    Eskenazi, Brenda; Harley, Kim; Bradman, Asa; Weltzien, Erin; Jewell, Nicholas P; Barr, Dana B; Furlong, Clement E; Holland, Nina T

    2004-07-01

    Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures. However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [beta(adjusted) = -0.41 weeks per log10 unit increase; 95% confidence interval (CI), -0.75 -- -0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (beta(adjusted) = 0.34 weeks per unit increase; 95% CI, 0.13-0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population.

  11. Comparative pulsation calculations with OP and OPAL opacities

    NASA Technical Reports Server (NTRS)

    Kanbur, Shashi M.; Simon, Norman R.

    1994-01-01

    Comparative linear nonadiabatic pulsation calculations are presented using the OPAL and Opacity Project opacities. The two sets of opacities include effects due to intermediate coupling and fine structure as well as new abundances. We used two mass luminosity (M-L) relations, one standard (BIT), and one employing substantial convective core overshoot (COV). The two sets of opacities cannot be differentiated on the basis of the stellar pulsation calculations presented here. The BIT relation can model the beat and bump Cepheids with masses between 4 and 7 solar mass, while if the overshoot relation is used, masses between 2 and 6 solar mass are required. In the RR Lyrae regime, we find the inferred masses of globular cluster RRd stars to be little influenced by the choice of OPAL or OP. Finally, the limited modeling we have done is not able to constrain the Cepheid M-L relation based upon period ratios observed in the beat and bump stars.

  12. Carbon quantum dots as fluorescence resonance energy transfer sensors for organophosphate pesticides determination.

    PubMed

    Wu, Xiaoli; Song, Yang; Yan, Xu; Zhu, Chengzhou; Ma, Yongqiang; Du, Dan; Lin, Yuehe

    2017-03-07

    Carbon quantum dots (CQDs) obtained from natural organics attract significant attention due to the abundance of carbon sources, varieties of heteroatom doping (such as N, S, P) and good biocompatibility of precursor. In this study, tunable fluorescence emission CQDs originated from chlorophyll were synthesized and characterized. The fluorescence emission can be effectively quenched by gold nanoparticles (Au NPs) via fluorescence resonance energy transfer (FRET). Thiocholine, which was produced from acetylthiocholine (ATC) by the hydrolysis of butyrylcholinesterase (BChE), could cause the aggregation of Au NPs and the corresponding recovery of FRET-quenched fluorescence emission. The catalytic activity of BChE could be irreversibly inhibited by organophosphorus pesticides (OPs), thus, the recovery effect was reduced. By evaluating the fluorescence emission intensity of CQDs, a FRET-based sensing platform for OPs determination was established. Paraoxon was studied as an example of OPs. The sensing platform displayed a linear relationship with the logarithm of the paraoxon concentrations in the range of 0.05-50μgL(-1) and the limit of detection (LOD) was 0.05μgL(-1). Real sample study in tap and river water revealed that this sensing platform was repeatable and accurate. The results indicate that the OP sensor is promising for applications in food safety and environmental monitoring.

  13. Gaze stability of observers watching Op Art pictures.

    PubMed

    Zanker, Johannes M; Doyle, Melanie; Robin, Walker

    2003-01-01

    It has been the matter of some debate why we can experience vivid dynamic illusions when looking at static pictures composed from simple black and white patterns. The impression of illusory motion is particularly strong when viewing some of the works of 'Op Artists, such as Bridget Riley's painting Fall. Explanations of the illusory motion have ranged from retinal to cortical mechanisms, and an important role has been attributed to eye movements. To assess the possible contribution of eye movements to the illusory-motion percept we studied the strength of the illusion under different viewing conditions, and analysed the gaze stability of observers viewing the Riley painting and control patterns that do not produce the illusion. Whereas the illusion was reduced, but not abolished, when watching the painting through a pinhole, which reduces the effects of accommodation, it was not perceived in flash afterimages, suggesting an important role for eye movements in generating the illusion for this image. Recordings of eye movements revealed an abundance of small involuntary saccades when looking at the Riley pattern, despite the fact that gaze was kept within the dedicated fixation region. The frequency and particular characteristics of these rapid eye movements can vary considerably between different observers, but, although there was a tendency for gaze stability to deteriorate while viewing a Riley painting, there was no significant difference in saccade frequency between the stimulus and control patterns. Theoretical considerations indicate that such small image displacements can generate patterns of motion signals in a motion-detector network, which may serve as a simple and sufficient, but not necessarily exclusive, explanation for the illusion. Why such image displacements lead to perceptual results with a group of Op Art and similar patterns, but remain invisible for other stimuli, is discussed.

  14. Bio-inspired Supramolecular Assemblies and Porous Materials for the Degradation of Organophosphate Nerve Agents

    NASA Astrophysics Data System (ADS)

    Totten, Ryan K.

    This thesis reports the synthesis of bio-inspired supramolecular assemblies and porous materials that are catalytically active in the degradation of organophosphate nerve agents. The first catalysts described are a series of cofacial metalloporphyrin dimers modeled after the active site of phosphotriesterase that were modularly prepared from a single porphyrin building block and shown to catalyze the methanolysis of p-nitrophenyl diphenyl phosphate (PNPDPP), a simulant for nerve agents. Notably, tuning the active sites inside the cavities of these dimers, from ZnII metal centers to Al-OMe moieties, affords an enhanced nucleophilic environment where a high concentration of methoxy ligands becomes available for reaction with encapsulated phosphate triesters. Up to a 1300-fold rate acceleration over the uncatalyzed reaction can be achieved via a combination of cavity-localized Lewis-acid activation and methoxide-induced methanolysis. Based on the design principles learned from the aforementioned solution-phase Al(porphyrin) dimers, a heterogeneous porous organic polymer (POP) catalyst was synthesized by incorporating an Al(porphyrin) functionalized with a large axial ligand into a POP using a cobalt-catalyzed acetylene trimerization strategy. Removal of the axial ligand afforded a microporous material that is capable of encapsulating and solvolytically degrading PNPDPP. Supercritical CO 2 processing of the Al(porphyrin)-based POP dramatically increased the pore size and volume, allowing for significantly higher catalytic activities. The syntheses of porphyrin-based POPs with tunable pore diameters and volumes have also been attempted. SnIV(porphyrins) functionalized with bulky trans-diaxial ligands can be incorporated into POPs. Post-synthesis removal of the ligands reveal POPs with a tunable range of micro- and mesopores as well as tunable pore volumes. Expanding upon the idea that active sites that can both bind substrates and deliver nucleophiles should be active

  15. Sperm viability and gene expression in honey bee queens (Apis mellifera) following exposure to the neonicotinoid insecticide Imidacloprid and the organophosphate Acaricide Coumaphos

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. UTC(OP) based on LNE-SYRTE atomic fountain primary frequency standards

    NASA Astrophysics Data System (ADS)

    Rovera, G. D.; Bize, S.; Chupin, B.; Guéna, J.; Laurent, Ph; Rosenbusch, P.; Uhrich, P.; Abgrall, M.

    2016-06-01

    UTC(OP), the French national realization of the international coordinated universal time, was redesigned and rebuilt. The first step was the implementation in October 2012 of a new algorithm based on a H-maser and on atomic fountain data. Thanks to the new implementation, the stability of UTC(OP) was dramatically improved and UTC(OP) competes with the best time scales available today. Then the hardware generation and distribution of the UTC(OP) physical signals were replaced. Part of the new hardware is composed of commercial devices, but the key elements were specifically developed. One of them is a special switch that allows the UTC(OP) signals to be derived from one of two time scales, based on two different H-masers, which are generated simultaneously. This insures the continuity of the UTC(OP) signal even when a change of the reference H-maser is required. With the new hardware implementation, UTC(OP) is made available through three coherent signals: 100 MHz, 10 MHz and 1 PPS. For more than 3 years, UTC(OP) remained well below 10 ns close to UTC, with a difference even less than 5 ns if we except a short period around MJD 56650.

  17. A Study of the Ethical Orientation of Co-op Students.

    ERIC Educational Resources Information Center

    Tillman, Robert L.

    1990-01-01

    A group of 255 civil engineering students in cooperative education programs responded to 12 hypothetical professional ethics situations in core areas of public interest. Findings showed that (1) co-op influences change from rule-based to act-based ethics; (2) students face ethical dilemmas during co-op; and (3) students considered the consequences…

  18. 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...

  19. 48 CFR 750.7110-3 - Submission of cases to the M/OP Director.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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...

  20. 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…

  1. Effects of dimethoate (30% EC), an organophosphate pesticide on liver of common carp, Cyprinus carpio.

    PubMed

    Singh, Ram Nayan

    2013-05-01

    Organ histopathology and changes in biochemical parameters in fish are good biomarkers of aquatic pollution. This study is an attempt to assess the effects of dimethoate, an organophosphate insecticide on the liver of common carp (C. carpio). Healthy individual fish were exposed to 0.40 mg l(-1) (25% of 96 hr LC50) concentration of dimethoate, for short term (96 hr). Liver of the exposed fish exhibited alterations like disruption of regular arrangement of hepatocytes, congestion and rupture of vessels; hemorrhage, cytoplasmic vacuolization, pyknotic nuclei and necrosis. Biochemical parameters viz. total liver protein (p < 0.001) and liver glycogen (p < 0.001) registered a significant decrease and blood glucose (p < 0.001) exhibited significant increase throughout exposure.

  2. [Plasma cholesterol determination in birds--a diagnostic tool for detection of organophosphate and carbamate intoxication].

    PubMed

    Kiesau, B; Kummerfeld, N

    1998-07-01

    An investigation was done on the clinical usefulness of the dry chemistry analyzer Vitros DT 60 II for determination of avian plasma cholinesterase. The analytical reliability of the method, evaluated by precision and accuracy, proved to be high for plasma of numerous pet and wild birds. Values of normal plasma-cholinesterase activity were established for different psittacine and European wild birds. Significant differences in physiologic plasma-cholinesterase activity were noted between closely related species as well as between juvenile and adult birds. These findings emphasize the necessity to use control values of the same species and age group for comparison. Dry chemistry plasma-cholinesterase determination can be used as a diagnostic tool for detection of organophosphate and carbamate poisonings in the majority of investigated birds.

  3. Development of a versatile organophosphorous-hydrolase-based assay for organophosphate pesticides

    NASA Astrophysics Data System (ADS)

    Rogers, Kim R.; Wang, Yi; Mulchandani, Ashok; Mulchandani, P.; Chen, Wilfred

    1999-02-01

    We report a rapid and versatile organophosphorus hydrolase (OPH)-based method for measurement of organophosphate pesticides. This assay is based on a substrate-dependant change in pH near the active site of the enzyme. The pH change is monitored using fluorescein isothiocyanate (FITC) which is covalently immobilized to the enzyme. This method employs FITC-labeled enzyme adsorbed to polymethylmethacrylate beads. Analytes were measured using a microbead fluorescence analyzer. The dynamic concentration range for the assay extends from 25 (mu) M to 400 (mu) M for paraoxon with a detection limit of 8 (mu) M. This assay compared favorably to an HPLC method for monitoring the concentration of coumaphos in bioremediation filtrate samples.

  4. An efficient thermostable organophosphate hydrolase and its application in pesticide decontamination.

    PubMed

    Del Giudice, Immacolata; Coppolecchia, Rossella; Merone, Luigia; Porzio, Elena; Carusone, Teresa Maria; Mandrich, Luigi; Worek, Franz; Manco, Giuseppe

    2016-04-01

    In vitro evolution of enzymes represents a powerful device to evolve new or to improve weak enzymatic functions. In the present work a semi-rational engineering approach has been used to design an efficient and thermostable organophosphate hydrolase, starting from a lactonase scaffold (SsoPox from Sulfolobus solfataricus). In particular, by in vitro evolution of the SsoPox ancillary promiscuous activity, the triple mutant C258L/I261F/W263A has been obtained which, retaining its inherent stability, showed an enhancement of its hydrolytic activity on paraoxon up to 300-fold, achieving absolute values of catalytic efficiency up to 10(5) M(-1) s(-1). The kinetics and structural determinants of this enhanced activity were thoroughly investigated and, in order to evaluate its potential biotechnological applications, the mutant was tested in formulations of different solvents (methanol or ethanol) or detergents (SDS or a commercial soap) for the cleaning of pesticide-contaminated surfaces.

  5. A Comparison of Multiple Esterases as Biomarkers of Organophosphate Exposure and Effect in Two Earthworm Species

    PubMed Central

    Schneider, Ashley; Stoskopf, Michael K.

    2011-01-01

    Two different earthworm species, Eisenia fetida and Lumbricus terrestris, were exposed to 5 μg/cm2 of malathion to evaluate their usefulness as sentinels of organophosphate exposure and to assess three different esterases, as biomarkers of malathion exposure and effect. Tissue xenobiotic burdens and esterase activity were determined for each species and each esterase in order to assess variability. E. fetida exhibited 4-fold less variability in tissue burdens than did L. terrestris and had less variable basal esterase activities. An attempt was made to correlate malathion and malaoxon tissue burdens with esterase activity post-exposure. There was no malaoxon present in the earthworm tissues. No significant correlations were determined by comparing acetylcholinesterase, butyrylcholinesterase, nor carboxylesterase activities with malathion burdens. PMID:21404045

  6. Persistence and residual activity of an organophosphate, pirimiphos-methyl, and three IGRs, hexaflumuron, teflubenzuron and pyriproxyfen, against the cowpea weevil, Callosobruchus maculatus (Coleoptera: Bruchidae).

    PubMed

    Abo-Elghar, Gamal E; El-Sheikh, Anwar E; El-Sayed, Ferial M; El-Maghraby, Hamdi M; El-Zun, Hesham M

    2004-01-01

    Three insect growth regulators (IGR), the chitin synthesis inhibitors (CSI) teflubenzuron and hexaflumuron and the juvenile hormone mimic (JHM) pyriproxyfen, as well as the organophosphate (OP) pirimiphos-methyl, were evaluated for their activity against the cowpea weevil, Callosobruchus maculatus (F), in cowpea seeds stored for up to 8 months post-treatment. The initial activity data showed that, based on LC50 level, teflubenzuron had strong ovicidal activity (LC50 = 0.056 mg kg(-1)) followed by pirimiphos-methyl (1.82 mg kg(-1)) and pyriproxyfen (91.9 mg kg(-1)). The residual activity data showed that none of the IGRs tested had strong activity when applied at 200 mg kg(-1) in reducing the oviposition rates of C maculatus at various storage intervals up to 8 months post-treatment. However, teflubenzuron reduced adult emergence (F1 progeny), achieving control ranging from 96.2% at 1 month to 94.3% at 8 months. Hexaflumuron showed a similar trend in its residual activity, ranging between 93.8% control at 1 month to 88.2% control at 8 months post-treatment. However, pyriproxyfen was more active than the CSIs tested and caused complete suppression (100% control) of adult emergence at all storage intervals. Unlike the IGRs tested, pirimiphos-methyl applied at 25 mg kg(-1) was more effective in reducing oviposition rates of C maculatus up to 8 months post-treatment. A strong reduction of adult emergence was also observed at various bimonthly intervals (98.6% control at 1 month to 91.6% control at 8 months post-treatment). The persistence of hexaflumuron and pirimiphos-methyl in cowpea seeds was also studied over a period of 8 months. The loss of hexaflumuron residue in treated cowpeas (200 mg kg(-1)) was very slow during the first month post-treatment (4.43%). At the end of 8 months, the residue level had declined significantly to 46.4% of the initial applied rate. The loss of pirimiphos-methyl residue in treated cowpeas (25 mg kg(-1)) was relatively high during the

  7. Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions

    PubMed Central

    Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

    2016-01-01

    Background: 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. Objectives: We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. Methods: 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. Results: 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. Conclusions: 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

  8. 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

  9. Elimination of organophosphate ester flame retardants and plasticizers in drinking water purification.

    PubMed

    Andresen, Jens; Bester, Kai

    2006-02-01

    Organophosphate ester flame retardants and plasticizers like tris-(2-chloro-, 1-methyl-ethyl)phosphate (TCPP), tris-(2-chloro-, 1-chloromethyl-ethyl)phosphate (TDCP), tris-(2-chloroethyl)phosphate (TCEP), tributylphosphates, triphenylphosphate (TPP), ethylhexyldiphenylphosphate (EHDPP) and tris-(butoxyethyl)phosphate (TBEP) have been studied in diverse processes for drinking water purification. The elimination efficiency of these different treatment processes, e.g., biological active slow underground passage, soil passage and technical treatment processes such as ozonization or multilayer and activated carbon filtration have been studied in three waterworks in the catchment area of the river Ruhr. In the untreated surface water the concentrations of the chlorinated organophosphates ranged 50-150 ng L(-1) TCPP, 10-130 ng L(-1) TCEP and 10-40 ng L(-1) TDCP. The amounts of the non-chlorinated alkylphosphates were in the same order of magnitude (40 ng L(-1) of the tributylphosphates, 170 ng L(-1) of TBEP and 10 ng L(-1) TPP) depending on weather and water flow. EHDPP was detected in the range of 1 ng L(-1). After the drinking water purification process in all waterworks in this study, the concentrations of the selected substances were below the respective limit of quantification (0.3-3 ng L(-1)). While activated carbon filtration as well as extended passage through soil (10-15 days residence time) were effective in eliminating all selected compounds, ozonization and multilayer filtration did not contribute to the elimination of the chlorinated compounds. The elimination effect of slow underground passage combined with soil passage concerning the halogenated compounds seemed to depend on the hydraulic residence time.

  10. Purification and characterization of methyl parathion hydrolase from Burkholderia cepacia capable of degrading organophosphate insecticides.

    PubMed

    Ekkhunnatham, Anirut; Jongsareejit, Boonsri; Yamkunthong, Wanphen; Wichitwechkarn, Jesdawan

    2012-04-01

    Methyl parathion hydrolase (MPH) from a methyl parathion-degrading Burkholderia cepacia indigenous to Thailand was purified to apparent homogeneity by three steps of column chromatography using Resource S, Sephadex G100, and Octyl Sepharose 4FF columns. Its molecular mass was determined to be 35 kDa, and the pI to be 8.5. The recombinant plasmid pGT1, containing the MPH-encoding gene, mpdB, cloned into pGEX-4T-2 was over-expressed in Escherichia coli as GST-MPH fusion protein. The recombinant MPH was purified to homogeneity by a single step, using GSTPrep FF affinity column, with the molecular mass identical to that of the native enzyme. The purified enzyme had the specific activity of about 1,600 unit mg(-1) protein and the yield of about 75%, a 39-fold increase in recovery compared to that of the native enzyme. The optimal temperature and pH were 25°C and 9.0, respectively. The MPH was stable, with its activity unchanged for 48 h at 4°C, and reduced to 50% after 5 h and to 45% after 48 h at 25°C. The enzyme activity remained 80-90% after 8-15 h at pH 6-7. Cd(2+), Co(2+), and Zn(2+) ions at the concentration of 1 mM enhanced the activity; while sodium dodecyl sulfate (SDS), dithiothreitol (DTT) and ethylenediaminetetraacetate (EDTA) reduced it. The enzyme also showed cross reactivity with other insecticides within the organophosphate group, and the kinetic parameters for individual substrates were investigated. Since MPH from B. cepacia has wide potential applications in detoxification and detection of organophosphate compounds, this study provides important basis for its future use.

  11. Effect of acetylcholinesterase (AChE) point-of-care testing in OP poisoning on knowledge, attitudes and practices of treating physicians in Sri Lanka

    PubMed Central

    2014-01-01

    Background Toxicology and Emergency medicine textbooks recommend measurement of acetylcholinesterase (AChE) in all symptomatic cases of organophosphorus (OP) poisoning but laboratory facilities are limited in rural Asia. The accuracy of point-of-care (POC) acetylcholinesterase testing has been demonstrated but it remains to be shown whether results would be valued by clinicians. This study aims to assess the effect of seeing AChE POC test results on the knowledge, attitudes and practices of doctors who frequently manage OP poisoning. Methods We surveyed 23 clinicians, who had different levels of exposure to seeing AChE levels in OP poisoned patients, on a) knowledge of OP poisoning and biomarker interpretation, b) attitudes towards AChE in guiding poison management, oxime therapy and discharge decisions, and c) practices of ordering AChE in poisoning scenarios. Results An overall high proportion of doctors valued the test (68-89%). However, we paradoxically found that doctors who were more experienced in seeing AChE results valued the test less. Lower proportions valued the test in guidance of acute poisoning management (50%, p = 0.015) and guidance of oxime therapy (25%, p = 0.008), and it was apparent it would not generally be used to facilitate early discharge. The highest proportion of respondents valued it on admission (p < 0.001). A lack of correlation of test results with the clinical picture, and a perception that the test was a waste of money when compared to clinical observation alone were also comments raised by some of the respondents. Greater experience with seeing AChE test results was associated with increased knowledge (p = 0.034). However, a disproportionate lack of knowledge on interpretation of biomarkers and the pharmacology of oxime therapy (12-50%) was noted, when compared with knowledge on the mechanism of OP poisoning and management (78-90%). Conclusions Our findings suggest an AChE POC test may not be valued by rural doctors. The practical

  12. Analysis of the detection of organophosphate pesticides in aqueous solutions using polymer-coated single IDT sensors

    NASA Astrophysics Data System (ADS)

    McCarthy, Michael

    The single interdigital transducer (IDT) device was investigated as a micro-chemical sensor for the detection of organophosphates compounds in aqueous solutions. The compounds of interest are: parathion, parathion-methyl, and paraoxon. The polymers used as a partially-selective coating for the direct detection of these compounds are 2,2'-diallylbisphenol A- 1,1,3,3,5,5-hexamethyltrisiloxane (BPA-HMTS) and polyepichlorohydrin (PECH). BPA-HMTS is synthesized here at Marquette University. The measurement of interest for the single IDT is the change radiation resistance. The radiation resistance represents the energy stored in the propagating acoustic wave. As analyte absorbs into the polymer coating, changes in the film's properties will undergo resulting in a change in the radiation resistance i.e the acoustic wave properties. The film's properties changing include: added mass, viscoelastic properties, thickness, and dielectric properties. These properties will contribute to an overall change in the radiation resistance. A linear change in the radiation resistance is expected to occur for increasing concentrations of an organophosphate. The experimental results indicate that BPA-HMTS shows greater sensitivity towards the organophosphates than PECH. Both polymers showed greatest to lowest sensitivity to parathion, parathion-methyl, and paraoxon respectively. Thicker films tested for both polymers, 0.75μm thick, show a higher response due to a more pronounced effect of mass loading than the thinner films tested, 0.50μm. The response times for BPA-HMTS were much faster than for PECH. Both films showed fastest to slowest response time to paraoxon, parathion-methyl, and parathion respectively. The sensor is tested for reproducibility for the polymer BP-HMTS. A sensor array consisting of separately tested devices from this work as well as work done by a previous student is utilized to increase the selectivity of the three organophosphates. Radial plots are performed for

  13. Emerging OP354-Like P[8] Rotaviruses Have Rapidly Dispersed from Asia to Other Continents.

    PubMed

    Zeller, Mark; Heylen, Elisabeth; Damanka, Susan; Pietsch, Corinna; Donato, Celeste; Tamura, Tsutomu; Kulkarni, Ruta; Arora, Ritu; Cunliffe, Nigel; Maunula, Leena; Potgieter, Christiaan; Tamim, Sana; Coster, Sarah De; Zhirakovskaya, Elena; Bdour, Salwa; O'Shea, Helen; Kirkwood, Carl D; Seheri, Mapaseka; Nyaga, Martin Monene; Mphahlele, Jeffrey; Chitambar, Shobha D; Dagan, Ron; Armah, George; Tikunova, Nina; Van Ranst, Marc; Matthijnssens, Jelle

    2015-08-01

    The majority of human group A rotaviruses possess the P[8] VP4 genotype. Recently, a genetically distinct subtype of the P[8] genotype, also known as OP354-like P[8] or lineage P[8]-4, emerged in several countries. However, it is unclear for how long the OP354-like P[8] gene has been circulating in humans and how it has spread. In a global collaborative effort 98 (near-)complete OP354-like P[8] VP4 sequences were obtained and used for phylogeographic analysis to determine the viral migration patterns. During the sampling period, 1988-2012, we found that South and East Asia acted as a source from which strains with the OP354-like P[8] gene were seeded to Africa, Europe, and North America. The time to the most recent common ancestor (TMRCA) of all OP354-like P[8] genes was estimated at 1987. However, most OP354-like P[8] strains were found in three main clusters with TMRCAs estimated between 1996 and 2001. The VP7 gene segment of OP354-like P[8] strains showed evidence of frequent reassortment, even in localized epidemics, suggesting that OP354-like P[8] genes behave in a similar manner on the evolutionary level as other P[8] subtypes. The results of this study suggest that OP354-like P[8] strains have been able to disperse globally in a relatively short time period. This, in combination with a relatively large genetic distance to other P[8] subtypes, might result in a lower vaccine effectiveness, underscoring the need for a continued surveillance of OP354-like P[8] strains, especially in countries where rotavirus vaccination programs are in place.

  14. Effects of a selective Rho-kinase inhibitor Y-27632 on oxidative stress parameters in acute dichlorvos poisoning in rats.

    PubMed

    Gunay, N; Kose, B; Demiryurek, S; Ocak, A R; Erel, O; Demiryurek, A T

    2008-10-01

    This study examined the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced acute toxicity in rats. Rats were randomly divided into four groups as control (corn oil), dichlorvos (30 mg kg(-1) i.p.), 1 and 10 mg kg(-1) Y-27632 + dichlorvos groups. Cholinergic signs (fatigue, tremor, cyanosis, hyper-secretion, fasciculations) were observed in all the rats in the dichlorvos group and the mortality rate was 50%. No cholinergic findings and deaths were observed in the control and Y-27632 groups. Plasma cholinesterase activities were suppressed with dichlorvos and these reductions were attenuated with Y-27632 pretreatment. There was a marked increase in plasma malondialdehyde level in the dichlorvos group, but Y-27632 pretreatment abolished this elevation. Dichlorvos markedly depressed cardiac paraoxonase activity, but these changes were not markedly modified with Y-27632. Total antioxidant capacities, total oxidant status, oxidative stress index, total free sulfhydryl groups and catalase activities in plasma and cardiac tissues were not markedly different between the groups. No significant changes were observed with cardiac myeloperoxidase activities or plasma arylesterase and ceruloplasmin activities. In conclusion, our results suggest that Rho-kinase pathway is involved in organophosphate intoxication, and a decrease in cardiac paraoxonase activities may play a role in the pathogenesis of acute organophosphate poisoning in rats.

  15. Kauai Island Utility Co-op (KIUC) PV integration study.

    SciTech Connect

    Ellis, Abraham; Mousseau, Tom

    2011-08-01

    This report investigates the effects that increased distributed photovoltaic (PV) generation would have on the Kauai Island Utility Co-op (KIUC) system operating requirements. The study focused on determining reserve requirements needed to mitigate the impact of PV variability on system frequency, and the impact on operating costs. Scenarios of 5-MW, 10-MW, and 15-MW nameplate capacity of PV generation plants distributed across the Kauai Island were considered in this study. The analysis required synthesis of the PV solar resource data and modeling of the KIUC system inertia. Based on the results, some findings and conclusions could be drawn, including that the selection of units identified as marginal resources that are used for load following will change; PV penetration will displace energy generated by existing conventional units, thus reducing overall fuel consumption; PV penetration at any deployment level is not likely to reduce system peak load; and increasing PV penetration has little effect on load-following reserves. The study was performed by EnerNex under contract from Sandia National Laboratories with cooperation from KIUC.

  16. Looking at Op Art: Gaze stability and motion illusions

    PubMed Central

    Hermens, Frouke; Zanker, Johannes

    2012-01-01

    Various Op artists have used simple geometrical patterns to create the illusion of motion in their artwork. One explanation for the observed illusion involves retinal shifts caused by small involuntary eye movements that observers make while they try to maintain fixation. Earlier studies have suggested a prominent role of the most conspicuous of these eye movements, small rapid position shifts called microsaccades. Here, we present data that could expand this view with a different interpretation. In three experiments, we recorded participants' eye movements while they tried to maintain visual fixation when being presented with variants of Bridget Riley's Fall, which were manipulated such as to vary the strength of induced motion. In the first two experiments, we investigated the properties of microsaccades for a set of stimuli with known motion strengths. In agreement with earlier observations, microsaccade rates were unaffected by the stimulus pattern and, consequently, the strength of induced motion illusion. In the third experiment, we varied the stimulus pattern across a larger range of parameters and asked participants to rate the perceived motion illusion. The results revealed that motion illusions in patterns resembling Riley's Fall are perceived even in the absence of microsaccades, and that the reported strength of the illusion decreased with the number of microsaccades in the trial. Together, the three experiments suggest that other sources of retinal image instability than microsaccades, such as slow oculomotor drift, should be considered as possible factors contributing to the illusion. PMID:23145284

  17. Monocrotophpos and dicrotophos residues in birds as a result of misuse of organophosphates in Matagorda County, Texas

    USGS Publications Warehouse

    Flickinger, Edward L.; White, D.H.; Mitchell, C.A.; Lamont, T.G.

    1984-01-01

    About 1100 birds of 12 species 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 weeks. The practice of illegally treating rice seed with either of these 2 organophosphates appears to be infrequent but widespread at present.

  18. Organophosphate-Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

    DTIC Science & Technology

    2013-10-01

    chlorpyrifos (CPF), and a representative, nerve agent, diisopropylfluorophosphate (DFP) in rats. The first year of this proposal has been dedicated...to date (N=4-6): 1) baseline MRI scans; 2) daily injections of vehicle or chlorpyrifos (3.0-18.0 mg/kg) x 14 days; 2) a second MRI scan on the day...affected individuals. We are studying two OPs, a representative insecticide that was used in the first gulf war, chlorpyrifos (CPF), and a

  19. Acute Bronchitis

    MedlinePlus

    ... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...

  20. Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Rac1.

    PubMed

    Wittmann, Torsten; Bokoch, Gary M; Waterman-Storer, Clare M

    2004-02-13

    In the leading edge of migrating cells, a subset of microtubules exhibits net growth in a Rac1- and p21-activated kinase-dependent manner. Here, we explore the possibility of whether phosphorylation and inactivation of the microtubule-destabilizing protein Op18/stathmin could be a mechanism regulating microtubule dynamics downstream of Rac1 and p21-activated kinases. We find that, in vitro, Pak1 phosphorylates Op18/stathmin specifically at serine 16 and inactivates its catastrophe promoting activity in biochemical and time lapse microscopy microtubule assembly assays. Furthermore, phosphorylation of either serine 16 or 63 is sufficient to inhibit Op18/stathmin in vitro. In cells, the microtubule-destabilizing effect of an excess of Op18/stathmin can be partially overcome by expression of constitutively active Rac1(Q61L), which is dependent on Pak activity, suggesting that the microtubule cytoskeleton can be regulated through inactivation of Op18/stathmin downstream of Rac1 and Pak in vivo. However, in vivo, Pak1 activity alone is not sufficient to phosphorylate Op18, indicating that additional pathways downstream of Rac1 are required for Op18 regulation.

  1. OpWise: Operons aid the identification of differentially expressedgenes in bacterial microarray experiments

    SciTech Connect

    Price, Morgan N.; Arkin, Adam P.; Alm, Eric J.

    2005-11-23

    Differentially expressed genes are typically identified by analyzing the variation between replicate measurements. These procedures implicitly assume that there are no systematic errors in the data even though several sources of systematic error are known. Results-OpWise estimates the amount of systematic error in bacterial microarray data by assuming that genes in the same operon have matching expression patterns. OpWise then performs a Bayesian analysis of a linear model to estimate significance. In simulations, OpWise corrects for systematic error and is robust to deviations from its assumptions. In several bacterial data sets, significant amounts of systematic error are present, and replicate-based approaches overstate the confidence of the changers dramatically, while OpWise does not. Finally, OpWise can identify additional changers by assigning genes higher confidence if they are consistent with other genes in the same operon. Although microarray data can contain large amounts of systematic error, operons provide an external standard and allow for reasonable estimates of significance. OpWise is available at http://microbesonline.org/OpWise.

  2. 7 CFR 1944.663 - Ownership agreement between HPG grantee and rental property owner or co-op.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... property owner or co-op. 1944.663 Section 1944.663 Agriculture Regulations of the Department of Agriculture... Preservation Grants § 1944.663 Ownership agreement between HPG grantee and rental property owner or co-op. HPG assistance may be provided by a grantee with respect to rental properties or co-ops only if the...

  3. 7 CFR 1944.663 - Ownership agreement between HPG grantee and rental property owner or co-op.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... property owner or co-op. 1944.663 Section 1944.663 Agriculture Regulations of the Department of Agriculture... Preservation Grants § 1944.663 Ownership agreement between HPG grantee and rental property owner or co-op. HPG assistance may be provided by a grantee with respect to rental properties or co-ops only if the...

  4. 7 CFR 1944.663 - Ownership agreement between HPG grantee and rental property owner or co-op.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... property owner or co-op. 1944.663 Section 1944.663 Agriculture Regulations of the Department of Agriculture... Preservation Grants § 1944.663 Ownership agreement between HPG grantee and rental property owner or co-op. HPG assistance may be provided by a grantee with respect to rental properties or co-ops only if the...

  5. 7 CFR 1944.663 - Ownership agreement between HPG grantee and rental property owner or co-op.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... property owner or co-op. 1944.663 Section 1944.663 Agriculture Regulations of the Department of Agriculture... Preservation Grants § 1944.663 Ownership agreement between HPG grantee and rental property owner or co-op. HPG assistance may be provided by a grantee with respect to rental properties or co-ops only if the...

  6. 7 CFR 1944.663 - Ownership agreement between HPG grantee and rental property owner or co-op.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... property owner or co-op. 1944.663 Section 1944.663 Agriculture Regulations of the Department of Agriculture... Preservation Grants § 1944.663 Ownership agreement between HPG grantee and rental property owner or co-op. HPG assistance may be provided by a grantee with respect to rental properties or co-ops only if the...

  7. Field resistance of Spodoptera litura (Lepidoptera: Noctuidae) to organophosphates, pyrethroids, carbamates and four newer chemistry insecticides in Hunan, China.

    PubMed

    Tong, Hong; Su, Qi; Zhou, Xiaomao; Bai, Lianyang

    2013-01-01

    The present studies were carried out to evaluate resistance in the populations of Spodoptera litura Fab. (Lepidoptera, Noctuidae) from five districts of Hunan Province in China to various insecticides from 2010 to 2012 using a standard leaf dip bioassay method. For organophosphates and pyrethroids, resistance ratios compared with a susceptible Lab-BJ strain were in the range of 14-229-fold for organophosphates and 12-227-fold for pyrethroids. Similarly, relative low levels of resistance to emamectin, indoxacarb, and chlorfenapyr were observed in all five populations. In contrast, the resistance to carbamates (thiodicarb or methomyl) was significantly higher than that of organophosphates, pyrethroids and newer chemistry insecticides. The pairwise correlation coefficients of LC50 values indicated that the newer chemistry insecticides and old generation insecticides were not significant except abamectin, which was negatively significantly correlated with methomyl. A significant correlation was observed between thiodicarb, methomyl, and deltamethrin, whereas resistance to bifenthrin showed no correlations with resistance to other insecticides except deltamethrin. The results are discussed in relation to integrated pest management for S. litura with special reference to management of field evolved resistance to insecticides.

  8. Toxicological and biochemical analysis of the susceptibility of sylvatic Triatoma infestans from the Andean Valley of Bolivia to organophosphate insecticide.

    PubMed

    Santo-Orihuela, Pablo Luis; Carvajal, Guillermo; Picollo, María Inés; Vassena, Claudia Viviana

    2013-09-01

    To increase our knowledge of the natural susceptibility of Triatoma infestans to an organophosphate insecticide, we performed toxicological and biochemical studies on three sylvatic populations from Bolivia and two populations from domestic dwellings from Bolivia and Argentina. Fifty-per-cent lethal doses (LD50) were determined based on the topical application of fenitrothion on first instar nymphs and mortality was assessed at 24 h. Both type of populations exhibited LD50ratios significantly higher than 1 with a range of the values (1.42-2.47); the maximum value were found in a sylvatic (-S) population, Veinte de Octubre-S. Samples were biochemically analysed using a glutathione S-transferase activity assay. The highest significant activity was obtained for Veinte de Octubre-S and the lowest activity was obtained for the reference population (102.69 and 54.23 pmol per minute per mg of protein respectively). Two out of the three sylvatic populations (Veinte de Octubre-S and Kirus Mayu-S) exhibited significantly higher glutathione S-transferase activity than that of the reference population. Based on this analysis of the natural susceptibility of this organism to organophosphate insecticides, continental and focal surveys of organophosphate susceptibility should be conducted to evaluate the evolution and distribution of this phenomenon.

  9. Toxicological and biochemical analysis of the susceptibility of sylvatic Triatoma infestans from the Andean Valley of Bolivia to organophosphate insecticide

    PubMed Central

    Santo-Orihuela, Pablo Luis; Carvajal, Guillermo; Picollo, María Inés; Vassena, Claudia Viviana

    2013-01-01

    To increase our knowledge of the natural susceptibility of Triatoma infestans to an organophosphate insecticide, we performed toxicological and biochemical studies on three sylvatic populations from Bolivia and two populations from domestic dwellings from Bolivia and Argentina. Fifty-per-cent lethal doses (LD50) were determined based on the topical application of fenitrothion on first instar nymphs and mortality was assessed at 24 h. Both type of populations exhibited LD50ratios significantly higher than 1 with a range of the values (1.42-2.47); the maximum value were found in a sylvatic (-S) population, Veinte de Octubre-S. Samples were biochemically analysed using a glutathione S-transferase activity assay. The highest significant activity was obtained for Veinte de Octubre-S and the lowest activity was obtained for the reference population (102.69 and 54.23 pmol per minute per mg of protein respectively). Two out of the three sylvatic populations (Veinte de Octubre-S and Kirus Mayu-S) exhibited significantly higher glutathione S-transferase activity than that of the reference population. Based on this analysis of the natural susceptibility of this organism to organophosphate insecticides, continental and focal surveys of organophosphate susceptibility should be conducted to evaluate the evolution and distribution of this phenomenon. PMID:24037203

  10. 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

  11. Seasonal fluctuation in susceptibility to insecticides within natural populations of Drosophila melanogaster. II. Features of genetic variation in susceptibility to organophosphate insecticides within natural populations of D. melanogaster.

    PubMed

    Miyo, Takahiro; Oguma, Yuzuru; Charlesworth, Brian

    2006-08-01

    To elucidate genetic variation in susceptibility to organophosphate insecticides within natural populations of Drosophila melanogaster, we conducted an analysis of variance for mortality data sets of isofemale lines (10-286 lines) used in the previous studies. Susceptibility of isofemale lines to the three organophosphate insecticides was continuously distributed within each natural population, ranging from susceptible to resistant. Analysis of variance showed highly significant variation among isofemale lines in susceptibility to each insecticide for each natural population. Significant genetic variances in susceptibility to the three chemicals were estimated for the Katsunuma population; 0.0529-0.2722 for malathion, 0.0492-0.1603 for prothiophos, and 0.0469-0.1696 for fenitrothion. Contrary to the consistent seasonal tendency towards an increase in mean susceptibility in the fall, reported in the previous study, genetic variances in susceptibility to the three organophosphates did not change significantly in 1997 but tended to increase by 2- to 5-times in 1998. We tested whether both the observed situations, maintenance and increase in genetic variance in organophosphate resistance, can be generated under circumstances in which the levels of resistance to the three organophosphates tended to decrease, by conducting a simulation analysis, based on the hypothesis that resistant genotypes have lower fitnesses than susceptible ones under the density-independent condition. The simulation analysis generally explained the pattern in the mean susceptibility and genetic variances in susceptibility to the three organophosphates, observed in the Katsunuma population of D. melanogaster. It was suggested that the differences in the frequencies of resistance genes in the summer population could affect the patterns in genetic variance in organophosphate resistance in the fall population.

  12. Detection of Organophosphate Flame Retardants in Furniture Foam and US House Dust

    PubMed Central

    Stapleton, Heather M.; Klosterhaus, Susan; Eagle, Sarah; Fuh, Jennifer; Meeker, John D.; Blum, Arlene; Webster, Thomas F.

    2009-01-01

    Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted in the increased use of alternate flame retardant chemicals to meet flammability standards. However, it has been difficult to determine which chemical formulations are currently being used in high volumes to meet flammability standards since the use of flame retardant formulations in consumer products is not transparent (i.e. not provided to customers). To investigate chemicals being used as replacements for PentaBDE in polyurethane foam, we analyzed foam samples from 26 different pieces of furniture purchased in the United States primarily between 2003 and 2009 using gas chromatography mass spectrometry. Samples included foam from couches, chairs, mattress pads, pillows, and, in one case, foam from a sound proofing system of a laboratory grade dust sieve. Fifteen of the foam samples contained the flame retardant tris(1,3-dichloro-2-propyl) phosphate (TDCPP; 1–5% by weight), four samples contained tris(1-chloro-2-propyl) phosphate (TCPP; 0.5 –2.2 % by weight), one sample contained brominated chemicals found in a new flame retardant mixture called Firemaster 550 (4.2% by weight), and one foam sample collected from a futon likely purchased prior to 2004 contained PentaBDE (0.5% by weight). Due to the high frequency of detection of the chlorinated phosphate compounds in furniture foam, we analyzed extracts from 50 house dust samples collected between 2002 and 2007 in the Boston, MA area for TDCPP, TCPP, and another high volume use organophosphate-based flame retardant used in foam, triphenylphosphate (TPP). Detection frequencies for TDCPP and TPP in the dust samples were >96% and were log normally distributed, similar to observations for PBDEs. TCPP was positively detected in dust in only 24% of the samples, but detection was significantly limited by a co-elution problem. The geometric mean concentrations for TCPP, TDCPP and TPP in house dust were 570, 1890, and 7360 ng/g, respectively

  13. Detection of organophosphate flame retardants in furniture foam and U.S. house dust.

    PubMed

    Stapleton, Heather M; Klosterhaus, Susan; Eagle, Sarah; Fuh, Jennifer; Meeker, John D; Blum, Arlene; Webster, Thomas F

    2009-10-01

    Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted in the increased use of alternate flame retardant chemicals to meet flammability standards. However, it has been difficult to determine which chemical formulations are currently being used in high volumes to meet flammability standards since the use of flame retardant formulations in consumer products is not transparent (i.e., not provided to customers). To investigate chemicals being used as replacements for PentaBDE in polyurethane foam, we analyzed foam samples from 26 different pieces of furniture purchased in the United States primarily between 2003 and 2009. Samples included foam from couches, chairs, mattress pads, pillows, and, in one case, foam from a sound-proofing system of a laboratory-grade dust sieve, and were analyzed using gas chromatography mass spectrometry. Fifteen of the foam samples contained the flame retardanttris(1,3-dichloro-2-propyl) phosphate (TDCPP; 1-5% by weight), four samples contained tris(1-chloro-2-propyl) phosphate (TCPP; 0.5 -22% by weight), one sample contained brominated chemicals found in a new flame retardant mixture called Firemaster 550 (4.2% by weight), and one foam sample collected from a futon likely purchased prior to 2004 contained PentaBDE (0.5% by weight). Due to the high frequency of detection of the chlorinated phosphate compounds in furniture foam,we analyzed extracts from 50 house dust samples collected between 2002 and 2007 in the Boston, MA area for TDCPP, TCPP, and another high volume use organophosphate-based flame retardant used in foam, triphenylphosphate (TPP). Detection frequencies for TDCPP and TPP in the dust samples were > 96% and were log normally distributed, similar to observations for PBDEs. TCPP was positively detected in dust in only 24% of the samples, but detection was significantly limited by a coelution problem. The geometric mean concentrations for TCPP, TDCPP, and TPP in house dust were 570, 1890, and 7360 ng

  14. 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.

  15. Three-photon absorption in optical parametric oscillators based on OP-GaAs

    NASA Astrophysics Data System (ADS)

    Heckl, Oliver H.; Bjork, Bryce J.; Winkler, Georg; Bryan Changala, P.; Spaun, Ben; Porat, Gil; Bui, Thinh Q.; Lee, Kevin F.; Jiang, Jie; Fermann, Martin E.; Schunemann, Peter G.; Ye, Jun

    2016-11-01

    We report on the first singly-resonant (SR), synchronously pumped optical parametric oscillator (OPO) based on orientation-patterned gallium arsenide (OP-GaAs). Together with a doubly resonant (DR) degenerate OPO based on the same OP-GaAs material, the output spectra cover 3 to 6 ${\\mu}$m within ~3 dB of relative power. The DR-OPO has the highest output power reported to date from a femtosecond, synchronously pumped OPO based on OP-GaAs. We discovered strong three photon absorption with a coefficient of 0.35 ${\\pm}$ 0.06 cm${^3}$/GW${^2}$ for our OP-GaAs sample, which limits the output power of these OPOs as mid-IR light sources. We present a detailed study of the three photon loss on the performance of both the SR and DR-OPOs, and compare them to those without this loss mechanism.

  16. 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

  17. 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.

  18. Music May Soothe the 'Savage Beast' of Post-Op Pain

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164526.html Music May Soothe the 'Savage Beast' of Post-Op ... pain and anxiety, but new research shows that music therapy may help ease their discomfort. Medication is ...

  19. 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.

  20. Common Post-Op Ear Drops Tied to Eardrum Perforations in Kids

    MedlinePlus

    ... gov/news/fullstory_164372.html Common Post-Op Ear Drops Tied to Eardrum Perforations in Kids Rate ... 2017 (HealthDay News) -- Children who suffer through multiple ear infections are often candidates for ear tube surgery. ...

  1. Usefulness of the Co-op Experience: A Study of Community College Students.

    ERIC Educational Resources Information Center

    Krebs, Uwe (Hugh)

    1987-01-01

    Analyzes the perceived usefulness of the co-op experience of community college graduates from the Production and Operating Management and the Marketing Management programs at Centennial College in Ontario. (JOW)

  2. Results of Investigations Concerning the Capabilities of the OpScan 100DM Optical Scanner.

    ERIC Educational Resources Information Center

    Gibbs, Gordon L.; Hooper, Judith

    A series of tests using OpScan 100DM optical scanner were carried out to determine whether it can mechanically transport paper that does not comply with the manufacturer's specifications for weight and size and see if standard paper stock has sufficient quality, opacity, and brightness to permit it to be used to print forms for the OpScan 100DM.…

  3. 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.

  4. OpEx - a validated, automated pipeline optimised for clinical exome sequence analysis

    PubMed Central

    Ruark, Elise; Münz, Márton; Clarke, Matthew; Renwick, Anthony; Ramsay, Emma; Elliott, Anna; Seal, Sheila; Lunter, Gerton; Rahman, Nazneen

    2016-01-01

    We present an easy-to-use, open-source Optimised Exome analysis tool, OpEx (http://icr.ac.uk/opex) that accurately detects small-scale variation, including indels, to clinical standards. We evaluated OpEx performance with an experimentally validated dataset (the ICR142 NGS validation series), a large 1000 exome dataset (the ICR1000 UK exome series), and a clinical proband-parent trio dataset. The performance of OpEx for high-quality base substitutions and short indels in both small and large datasets is excellent, with overall sensitivity of 95%, specificity of 97% and low false detection rate (FDR) of 3%. Depending on the individual performance requirements the OpEx output allows one to optimise the inevitable trade-offs between sensitivity and specificity. For example, in the clinical setting one could permit a higher FDR and lower specificity to maximise sensitivity. In contexts where experimental validation is not possible, minimising the FDR and improving specificity may be a preferable trade-off for slightly lower sensitivity. OpEx is simple to install and use; the whole pipeline is run from a single command. OpEx is therefore well suited to the increasing research and clinical laboratories undertaking exome sequencing, particularly those without in-house dedicated bioinformatics expertise. PMID:27485037

  5. Neuroprotection against diisopropylfluorophosphate in acute hippocampal slices

    PubMed Central

    Ferchmin, P. A.; Pérez, Dinely; Cuadrado, Brenda L.; Carrasco, Marimée; Martins, Antonio H.; Eterović, Vesna A.

    2015-01-01

    Diisopropylfluorophosphate (DFP) is an irreversible inhibitor of acetylcholine esterase (AChE) and a surrogate of the organophosphorus (OP) nerve agent sarin. The neurotoxicity of DFP was assessed as a reduction of population spike (PS) area elicited by synaptic stimulation in acute hippocampal slices. Two classical antidotes, atropine, and pralidoxime, and two novel antidotes, 4R-cembranotriene-diol (4R) and a caspase 9 inhibitor, were tested. Atropine, pralidoxime, and 4R significantly protected when applied 30 min after DFP. The caspase inhibitor was neuroprotective when applied 5–10 min before or after DFP, suggesting that early synaptic apoptosis is responsible for the loss of PSs. It is likely that apoptosis starts at the synapses and, if antidotes are not applied, descends to the cell bodies, causing death. The acute slice is a reliable tool for mechanistic studies, and the assessment of neurotoxicity and neuroprotection with PS areas is, in general, pharmacologically congruent with in vivo results and predicts the effect of drugs in vivo. 4R was first found to be neuroprotective in slices and later we demonstrated that 4R is neuroprotective in vivo. The mechanism of neurotoxicity of OPs is not well understood, and there is a need for novel antidotes that could be discovered using acute slices. PMID:26438150

  6. Pediatric Acute Lymphoblastic Leukemia and Exposure to Pesticides

    PubMed Central

    Soldin, Offie P.; Nsouly-Maktabi, Hala; Genkinger, Jeanine M.; Loffredo, Christopher A.; Ortega-Garcia, Juan Antonio; Colantino, Drew; Barr, Dana B.; Luban, Naomi L.; Shad, Aziza T.; Nelson, David

    2013-01-01

    Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case–control study of children newly diagnosed with ALL, and their mothers (n = 41 child–mother pairs) were recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography–high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association. PMID:19571777

  7. Pediatric acute lymphoblastic leukemia and exposure to pesticides.

    PubMed

    Soldin, Offie P; Nsouli-Maktabi, Hala; Nsouly-Maktabi, Hala; Genkinger, Jeanine M; Loffredo, Christopher A; Ortega-Garcia, Juan Antonio; Colantino, Drew; Barr, Dana B; Luban, Naomi L; Shad, Aziza T; Nelson, David

    2009-08-01

    Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case-control study of children newly diagnosed with ALL, and their mothers (n = 41 child-mother pairs) recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography-high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association.

  8. Metabolism, Seizures, and Blood Flow in Brain Following Organophosphate Exposure: Mechanisms of Action and Possible Therapeutic Agents

    DTIC Science & Technology

    1991-01-31

    metabolism In all brain regions. Metabolite transport systems of brain microvasculature were uninhibited by OP exposure. Studies using L-(1- 14C]leudne and...suggest another means of Ch production. Blood-brain transport of lysophosphaiidylcholine is not a significant source of Ch or phospholipid precursors. A... transport studies ind•cated that a small increase In metabolite (glucose, leucine, glycdne, and choline (Ch]) influx occurred during the first 20 min of OP

  9. Ln3+-Catalyzed Alcoholysis of Organophosphates: New Methodology for the Catalytic Transformation of Phosphorus Pesticides and CW Agents

    DTIC Science & Technology

    2007-03-14

    equivalent of alkoxide, provided an efficient catalyst capable of decomposing all P=O classes of the above neutral OP agents (except P=S derivatives...triazacyclododecane, as their monoalkoxy forms, are also powerful catalysts for decomposing these OP materials, including the P=S examples. Considerable study...was devoted to determining the mechanism of the reactions which is suggested to involve a dual role for the catalyst as both a Lewis acid and

  10. Sulfhydryl-specific PEGylation of phosphotriesterase cysteine mutants for organophosphate detoxification.

    PubMed

    Daffu, Gurdip K; Lopez, Patricia; Katz, Francine; Vinogradov, Michael; Zhan, Chang-Guo; Landry, Donald W; Macdonald, Joanne

    2015-11-01

    The catalytic bioscavenger phosphotriesterase (PTE) is experimentally an effective antidote for organophosphate poisoning. We are interested in the molecular engineering of this enzyme to confer additional functionality, such as improved in vivo longevity. To this aim, we developed PTE cysteine mutants with free sulfhydryls to allow macromolecular attachments to the protein. A library of PTE cysteine mutants were assessed for efficiency in hydrolysing the toxic pesticide metabolite paraoxon, and screened for attachment with a sulfhydryl-reactive small molecule, fluorescein 5-maleimide (F5M), to examine cysteine availability. We established that the newly incorporated cysteines were readily available for labelling, with R90C, E116C and S291C displaying the highest affinity for binding with F5M. Next, we screened for efficiency in attaching a large macromolecule, a 30 000 Da polyethylene glycol (PEG) molecule. Using a solid-phase PEGylation strategy, we found the E116C mutant to be the best single-mutant candidate for attachment with PEG30. Kinetic activity of PEGylated E116C, with paraoxon as substrate, displayed activity approaching that of the unPEGylated wild-type. Our findings demonstrate, for the first time, an efficient cysteine mutation and subsequent method for sulfhydryl-specific macromolecule attachment to PTE.

  11. The impact of organophosphate pesticides in orchards on earthworms in the Western Cape, South Africa.

    PubMed

    Reinecke, S A; Reinecke, A J

    2007-02-01

    Earthworm population density was measured in and adjacent to an orchard in an agricultural area in the Western Cape, South Africa. Worm densities were very low in orchards (22/m(2)) compared to adjacent uncultivated fields (152/m(2)) at a distance from the orchards. The possible effect of organophosphate pesticides on the earthworms was investigated. Background soil concentrations of chlorpyrifos prior to the start of the spraying season were low (0.2-2.7 microg/kg) but persistent for up to 6 months after the last spraying event, and the pesticide was, as a result of rainfall, transported to nontarget areas by runoff. Background concentrations of azinphos methyl were higher than those of chlorpyrifos (1.6-9.8 microg/kg) but not detectable 2 weeks after a spraying event. Azinphos methyl was mostly transported by wind (spray drift) to adjacent areas. A microcosm study indicated effects of chlorpyrifos on earthworms as determined by measuring biomass change and Cholinesterase inhibition. It is concluded that earthworms were affected detrimentally by the pesticides due to chronic (chlorpyrifos) and intermittent (azinphos methyl) exposure.

  12. Bioaccumulation of Dechloranes, organophosphate esters, and other flame retardants in Great Lakes fish.

    PubMed

    Guo, Jiehong; Venier, Marta; Salamova, Amina; Hites, Ronald A

    2017-04-01

    We measured the concentrations of 60 flame retardants (and related compounds) in fish samples collected in the Great Lakes basin. These analytes include dechlorane-related compounds (Decs), organophosphate esters (OPEs), and brominated flame retardants (BFRs). Composite lake trout (Salvelinus namaycush) or walleye (Sander vitreus, from Lake Erie) samples were collected (N=3 for each lake) in 2010 from each of the five Great Lakes (a total of 15 samples). Among the dechlorane-related compounds, Dechlorane, Dechlorane Plus, Dechlorane-602, Dechlorane-603, and Dechlorane-604 (with zero to three bromines and with four chlorines) were detected in >73% of the fish samples. The concentrations of some of these dechlorane-related compounds were 3-10 times higher in Lake Ontario trout than in fish from the other four lakes. Tris(1-chloroisopropyl) phosphate, tri-n-butylphosphate, tris(2-chloroethyl)phosphate, and triphenyl phosphate were found in >50% of the fish samples. Polybrominated diphenyl ethers (PBDEs) were the most abundant of the flame retardants in fish, with a mean concentration of 250ng/g lipid. Our findings suggest that the Decs and BFRs with 3-6 bromines are more bioaccumulative in the fish than the OPEs and high molecular weight BFRs.

  13. Phosphate-solubility and phosphatase activity in Gangetic alluvial soil as influenced by organophosphate insecticide residues.

    PubMed

    Majumder, Shyam Prasad; Das, Amal Chandra

    2016-04-01

    An experiment was conducted under laboratory conditions to investigate the effect of four organophosphate insecticides, viz. monocrotophos, profenophos, quinalphos and triazophos at their field application rates (0.75, 1.0, 0.5 and 0.6 kg a.i.ha(-1), respectively), on the growth and activities of phosphate solubilizing microorganisms in relation to availability of insoluble phosphates in the Gangetic alluvial soil of West Bengal, India. The proliferation of phosphate solubilizing microorganisms was highly induced with profenophos (38.3%), while monocrotophos exerted maximum stimulation (20.8%) towards the solubility of insoluble phosphates in soil. The phosphatase activities of the soil (both acid phosphatase and alkaline phosphatase) were significantly increased due to the incorporation of the insecticides in general, and the augmentation was more pronounced with quinalphos (43.1%) followed by profenophos (27.6%) for acid phosphatase, and with monocrotophos (25.2%) followed by profenophos (16.1%) for alkaline phosphatase activity in soil. The total phosphorus was highly retained by triazophos (19.9%) followed by monocrotophos (16.5%), while incorporation of triazophos and quinalphos manifested greater availability of water soluble phosphorus in soil.

  14. Brominated and organophosphate flame retardants in selected consumer products on the Japanese market in 2008.

    PubMed

    Kajiwara, Natsuko; Noma, Yukio; Takigami, Hidetaka

    2011-09-15

    The concentrations of traditional brominated flame retardants (BFRs) and organophosphate flame retardants (OPFRs) in new consumer products, including electronic equipment, curtains, wallpaper, and building materials, on the Japanese market in 2008 were investigated. Although some components of the electronic equipment contained bromine at concentrations on the order of percent by weight, as indicated by X-ray fluorescence analysis, the bromine content could not be fully accounted for by the BFRs analyzed in this study, which included polybrominated diphenylethers, decabromodiphenyl ethane, tetrabromobisphenol A, polybromophenols, and hexabromocyclododecanes. These results suggest the use of alternative BFRs such as newly developed formulations derived from tribromophenol, tetrabromobisphenol A, or both. Among the 11 OPFRs analyzed, triphenylphosphate was present at the highest concentrations in all the products investigated, which suggests the use of condensed-type OPFRs as alternative flame retardants, because they contain triphenylphosphate as an impurity. Tripropylphosphate was not detected in any samples; and trimethylphosphate, tributyl tris(2-butoxyethyl)phosphate, and tris(1,3-dichloro-2-propyl)phosphate were detected in only some components and at low concentrations. Note that all the consumer products evaluated in this study also contained traditional BFRs in amounts that were inadequate to impart flame retardancy, which implies the incorporation of recycled plastic materials containing BFRs that are of global concern.

  15. Kinetic mechanism of the detoxification of the organophosphate paraoxon by human serum A-esterase.

    PubMed

    Vitarius, J A; Sultatos, L G

    1994-01-01

    The mammalian detoxification of certain organophosphates, such as paraoxon [O,O-diethyl (p-nitrophenyl) phosphate], is catalyzed by the enzyme A-esterase. In this study, incubations of human serum in 50 mM glycine buffer (pH 10.5) with paraoxon resulted in the nonlinear production of p-nitrophenol, characterized by a rapid initial phase for the first several minutes of the incubation, followed by a second, slower phase in which the velocity approached constancy. Production of p-nitrophenol could be accurately fitted to the velocity equation for an Ordered Uni Bi kinetic mechanism with initial-burst activity, yielding estimates of appk2, appk3, and appE, for 10 human subjects. Increasing calcium concentration in the incubation resulted in increases in appk3 and appE, without affecting appk2. Conversely, addition of 1 M sodium chloride decreased the appk3 and appE, but did not alter appk2. And finally, a continuous system computer model was constructed based on the differential equations descriptive of an Ordered Uni Bi kinetic mechanism. This model accurately simulated production of p-nitrophenol from human serum, providing further support that A-esterase hydrolyzes paraoxon by an Ordered Uni Bi kinetic mechanism with initial-burst activity.

  16. Measuring Personal Exposure to Organophosphate Flame Retardants Using Silicone Wristbands and Hand Wipes.

    PubMed

    Hammel, Stephanie C; Hoffman, Kate; Webster, Thomas F; Anderson, Kim A; Stapleton, Heather M

    2016-04-19

    Organophosphate flame retardants (PFRs) are widely used as replacements for polybrominated diphenyl ethers in consumer products. With high detection in indoor environments and increasing toxicological evidence suggesting a potential for adverse health effects, there is a growing need for reliable exposure metrics to examine individual exposures to PFRs. Silicone wristbands have been used as passive air samplers for quantifying exposure in the general population and occupational exposure to polycyclic aromatic hydrocarbons. Here we investigated the utility of silicone wristbands in measuring exposure and internal dose of PFRs through measurement of urinary metabolite concentrations. Wristbands were also compared to hand wipes as metrics of exposure. Participants wore wristbands for 5 consecutive days and collected first morning void urine samples on 3 alternating days. Urine samples were pooled across 3 days and analyzed for metabolites of the following PFRs: tris(1,3-dichloroisopropyl) phosphate (TDCIPP), tris(1-chloro-2-isopropyl) phosphate (TCIPP), triphenyl phosphate (TPHP), and monosubstituted isopropylated triaryl phosphate (mono-ITP). All four PFRs and their urinary metabolites were ubiquitously detected. Correlations between TDCIPP and TCIPP and their corresponding urinary metabolites were highly significant on the wristbands (rs = 0.5-0.65, p < 0.001), which suggest that wristbands can serve as strong predictors of cumulative, 5-day exposure and may be an improved metric compared to hand wipes.

  17. Organophosphate ester (OPE) flame retardants and plasticizers in the open Mediterranean and Black Seas atmosphere.

    PubMed

    Castro-Jiménez, Javier; Berrojalbiz, Naiara; Pizarro, Mariana; Dachs, Jordi

    2014-03-18

    The presence of organophosphate ester (OPE) flame retardants and plasticizers has been confirmed for the first time in the atmosphere over the Mediterranean and Black Seas. Atmospheric aerosol samples were collected during two West-East oceanographic cruises across the Mediterranean and in the southwest Black Sea. This comprehensive assessment of baseline concentrations of aerosol phase OPEs, spatial distribution, and related deposition fluxes reveals levels ranging from 0.4 to 6.0 ng m(-3) for the ∑14OPEs and a lack of significant differences among sub-basins. Levels measured across the Mediterranean Sea and in the Black Sea are in the upper range or higher than those from previous reports for the marine atmosphere, presumably due to proximity to sources. From 13 to 260 tons of OPEs are estimated to be annually loaded to the Mediterranean Sea open waters from the atmosphere. Tris-(1-chloro-2-propyl)phosphate (TCPP) was the most abundant compound over the atmosphere of all the Mediterranean and Black Sea sub-basins, and therefore the chemical reaching surface waters at a higher extent by dry deposition. The atmospheric deposition fluxes of phosphorus due to OPE deposition is a significant fraction of known atmospheric inputs of new organic phosphorus (P), suggesting the relevant role that anthropogenic organic pollutants could play in the P cycle.

  18. Occurrence and dry deposition of organophosphate esters in atmospheric particles over the northern South China Sea.

    PubMed

    Lai, Senchao; Xie, Zhiyong; Song, Tianli; Tang, Jianhui; Zhang, Yingyi; Mi, Wenying; Peng, Jinhu; Zhao, Yan; Zou, Shichun; Ebinghaus, Ralf

    2015-05-01

    Nine organophosphate esters (OPEs) in airborne particles were measured during a cruise campaign over the northern South China Sea (SCS) from September to October 2013. The concentration of the total OPEs (∑OPEs) was 47.1-160.9 pg m(-3), which are lower than previous measurements in marine atmosphere environments. Higher OPE concentrations were observed in terrestrially influenced samples, suggesting that OPE concentrations were significantly influenced by air mass transport. Chlorinated OPEs were the dominant OPEs, accounting for 65.8-83.7% of the ∑OPEs. Tris-(2-chloroethyl) phosphate (TCEP) was the predominant OPE compound in the samples (45.0±12.1%), followed by tris-(1-chloro-2-propyl) phosphates (TCPPs) (28.8±8.9%). Dry particle-bound deposition fluxes ranged from 8.2 to 27.8 ng m(-2) d(-1) for the ∑OPEs. Moreover, the dry deposition input of the ∑OPEs was estimated to be 4.98 ton y(-1) in 2013 in a vast area of northern SCS. About half of the input was found to relate to air masses originating from China.

  19. Effects of metal and organophosphate mixtures on Ceriodaphnia dubia survival and reproduction.

    PubMed

    Mahar, Amy M; Watzin, Mary C

    2005-07-01

    The toxicity of mixtures of copper, zinc, and diazinon were determined for Ceriodaphnia dubia using 7-d survival and reproduction tests. Fifteen treatments, including combinations of the chemicals at 0, 25, 50, 75, and 100% of their individual median lethal concentrations, adding up to one toxic unit (TU) were tested. The TU was then used to classify each mixture response as additive, greater than additive, or less than additive. For survival, additive responses occurred in the 75% zinc plus 25% diazinon and the 50% copper plus 25% zinc plus 25% diazinon treatments. For reproduction, additive responses occurred in the 75% copper plus 25% zinc, 75% copper plus 25% diazinon, and 75% zinc plus 25% diazinon treatments. Copper and zinc played a greater role in toxicity than diazinon did. Less-than-additive interactions were found in all remaining mixtures, perhaps because of differences in mode of action between diazinon and metals. Consideration of dose-response curves can help to explain inconsistencies regarding toxic response in treatments with different ratios of the same chemicals. As TU percentages changed, mixture components were taken from different locations on differently shaped dose-response curves. Because most responses were less than additive, however, water-quality criteria based on individual concentrations probably are protective for most metal-organophosphate mixtures.

  20. Effects of primary metabolites of organophosphate flame retardants on transcriptional activity via human nuclear receptors.

    PubMed

    Kojima, Hiroyuki; Takeuchi, Shinji; Van den Eede, Nele; Covaci, Adrian

    2016-03-14

    Organophosphate flame retardants (OPFRs) have been used in a wide variety of applications and detected in several environmental matrices, including indoor air and dust. Continuous human exposure to these chemicals is of growing concern. In this study, the agonistic and/or antagonistic activities of 12 primary OPFR-metabolites against ten human nuclear receptors were examined using cell-based transcriptional assays, and compared to those of their parent compounds. As a result, 3-hydroxylphenyl diphenyl phosphate and 4-hydroxylphenyl diphenyl phosphate showed more potent estrogen receptor α (ERα) and ERβ agonistic activity than did their parent, triphenyl phosphate (TPHP). In addition, these hydroxylated TPHP-metabolites also showed ERβ antagonistic activity at higher concentrations and exhibited pregnane X receptor (PXR) agonistic activity as well as androgen receptor (AR) and glucocorticoid receptor (GR) antagonistic activities at similar levels to those of TPHP. Bis(2-butoxyethyl) 3'-hydroxy-2-butoxyethyl phosphate and 2-hydroxyethyl bis(2-butoxyethyl) phosphate act as PXR agonists at similar levels to their parent, tris(2-butoxyethyl) phosphate. On the other hand, seven diester OPFR-metabolites and 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate did not show any receptor activity. Taken together, these results suggest that hydroxylated TPHP-metabolites show increased estrogenicity compared to the parent compound, whereas the diester OPFR-metabolites may have limited nuclear receptor activity compared to their parent triester OPFRs.

  1. Hair and Nails as Noninvasive Biomarkers of Human Exposure to Brominated and Organophosphate Flame Retardants.

    PubMed

    Liu, Liang-Ying; He, Ka; Hites, Ronald A; Salamova, Amina

    2016-03-15

    After the phase-out of polybrominated diphenyl ethers (PBDEs), the use of alternative flame retardants (AFRs), such as FireMaster 550, and of organophosphate esters (OPEs) has increased. However, little is known about human exposure to these chemicals. This lack of biomonitoring studies is partially due to the absence of reliable noninvasive biomarkers of exposure. Human hair and nails can provide integrated exposure measurements, and as such, these matrices can potentially be used as noninvasive biomarkers of exposure to these flame retardants. Paired human hair, fingernail, toenail, and serum samples obtained from 50 adult participants recruited at Indiana University Bloomington campus were analyzed by gas chromatographic mass spectrometry for 36 PBDEs, 9 AFRs, and 12 OPEs. BDE-47, BDE-99, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), di(2-ethylhexyl) tetrabromophthalate (TBPH), tris(1,3-dichloro-2-propyl)phosphate (TDCIPP), and triphenyl phosphate (TPHP) were the most abundant compounds detected in almost all hair, fingernail, and toenail samples. The concentrations followed the order OPEs > TBB+TBPH > Σpenta-BDE. PBDE levels in the hair and nail samples were significantly correlated with their levels in serum (P < 0.05), suggesting that human hair and nails can be used as biomarkers to assess human exposure to PBDEs.

  2. Mutagenicity Assessment of Organophosphates using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Assay

    PubMed Central

    Bhinder, Preety; Chaudhry, Asha

    2013-01-01

    Objectives: In this study we have evaluated the mutagenicity of organophosphate pesticides acephate, chlorpyrifos, and profenofos using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with the mosquito Culex quinquefasciatus taken as an experimental model. Materials and Methods: Second instar larvae were treated with LC20 of each pesticide for 24 h and mutations induced in the sequence of mitochondrial COII gene (690bp) were studied from restriction patterns generated with AluI, PacI, and PsiI restriction endonucleases. Results: Variations in the number and size of digested fragments were recorded from treated individuals compared with controls showing that the restriction enzymes created a cut at different locations. In addition, sequences of COII gene from control and treated individuals were also used to confirm the RFLP patterns. From the sequence alignment data, it was found that mutations caused the destruction and generation of restriction sites in the gene sequence of treated individuals. Conclusion: This study indicates that all the three pesticides had potential to induce mutations in the normal sequence of COII gene and also advocates the use of PCR-RFLP assay as an efficient, rapid, and sensitive technique to detect mutagenicity of pesticides. PMID:24403735

  3. Airborne organophosphate pesticides drift in Mediterranean climate: The importance of secondary drift

    NASA Astrophysics Data System (ADS)

    Zivan, Ohad; Segal-Rosenheimer, Michal; Dubowski, Yael

    2016-02-01

    Pesticide application is a short-term air-pollution episode with near and far field effects due to atmospheric drift. In order to better evaluate resulting air concentrations in nearby communities following pesticide application, measurements of airborne pesticides were conducted at ∼70 m from field edge. This was done following three different application events of the organophosphate pesticide Chlorpyrifos in a persimmon orchard. Complementary information on larger spatial scale was obtained using CALPUFF modeling in which application and meteorological data was used to better evaluate dispersion patterns. Measurements indicated high airborne concentrations during application hours (few μg m-3 for 8 h average), which dropped to tens of ng m-3 in the following days. Measured atmospheric concentrations show that secondary drift (i.e., post-application drift) involves significant loads of pesticides and hence should not be ignored in exposure considerations. Furthermore, CALPUFF modeling revealed the complex dispersion pattern when weak winds prevailed, and showed that during the 24 h after application air concentrations reached levels above the hourly Texas effect screening level (0.1 μg m-3). Interestingly, weak winds on the night after application resulted in a secondary peak in measured and modeled air concentrations. Long exposure time (when secondary drift is considered) and concentrations measured following such common air-assisted orchard application, suggest pesticide drift may have health repercussions that are currently unknown, and emphasize the need for further epidemiological studies.

  4. Mechanism of inhibition of lysyl hydroxylase activity by the organophosphates malathion and malaoxon.

    PubMed

    Samimi, A; Last, J A

    2001-11-01

    Direct inhibition of lysyl hydroxylase by malathion and malaoxon was observed in an in vitro enzyme assay with recombinant lysyl hydroxylase expressed via a baculoviral system. The IC50 values for malathion and malaoxon were estimated to be approximately 60 and 45 mM, respectively. Additional kinetic studies showed this inhibition to be competitive or partially competitive with respect to the synthetic (collagen) peptide, partially uncompetitive with respect to Fe(2+), and partially noncompetitive with respect to ascorbic acid. The calculated values for the K(i) were consistent with the IC50 values. Allosteric effects were not found for any of the cofactors tested, the peptide substrate, or the inhibitors. Interactions were found to be unimolecular for lysyl hydroxylase and its substrate and cofactors as well as for the inhibitors malathion and malaoxon. A computer search of a protein structure database showed an unexpected region of partial homology between the active site sequence of acetylcholinesterase and a segment of lysyl hydroxylase, suggesting a possible molecular basis for these observations. These results suggest the possibility of a novel and hitherto unexpected class of inhibitors of lysyl hydroxylase, based on the organophosphate structure, that might be of value for testing as antifibrotic drugs.

  5. Immobilization of the enzyme GpdQ on magnetite nanoparticles for organophosphate pesticide bioremediation.

    PubMed

    Daumann, Lena J; Larrabee, James A; Ollis, David; Schenk, Gerhard; Gahan, Lawrence R

    2014-02-01

    Annually thousands of people die or suffer from organophosphate (pesticide) poisoning. In order to remove these toxic compounds from the environment, the use of enzymes as bioremediators has been proposed. We report here a Ser127Ala mutant based on the enzyme glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes. The mutant, with improved metal binding abilities, has been immobilized using glutaraldehyde on PAMAM dendrimer-modified magnetite nanoparticles. The immobilized system was characterized using elemental analysis as well as infrared, transmission electron and X-ray photoelectron spectroscopies. The amount of GpdQ that was immobilized with the optimized procedure was 1.488 nmol per g MNP. A kinetic assay has been designed to evaluate the activity of the system towards organophosphoester substrates. The specific activity towards BPNPP directly after immobilization was 3.55 μmol mg(-1)min(-1), after one week 3.39 μmol mg(-1)min(-1) and after 120 days 3.36 μmol mg(-1)min(-1), demonstrating that the immobilized enzyme was active for multiple cycles and could be stored on the nanoparticles for a prolonged period.

  6. Photonic crystal sensor for organophosphate nerve agents utilizing the organophosphorus hydrolase enzyme.

    PubMed

    Walker, Jeremy P; Kimble, Kyle W; Asher, Sanford A

    2007-12-01

    We developed an intelligent polymerized crystalline colloidal array (IPCCA) photonic crystal sensing material which reversibly senses the organophosphate compound methyl paraoxon at micromolar concentrations in aqueous solutions. A periodic array of colloidal particles is embedded in a poly-2-hydroxyethylacrylate hydrogel. The particle lattice spacing is such that the array Bragg-diffracts visible light. We utilize a bimodular sensing approach in which the enzyme organophosphorus hydrolase (OPH) catalyzes the hydrolysis of methyl paraoxon at basic pH, producing p-nitrophenolate, dimethylphosphate, and two protons. The protons lower the pH and create a steady-state pH gradient. Protonation of the phenolates attached to the hydrogel makes the free energy of mixing of the hydrogel less favorable, which causes the hydrogel to shrink. The IPCCA's lattice constant decreases, which blueshifts the diffracted light. The magnitude of the steady-state diffraction blueshift is proportional to the concentration of methyl paraoxon. The current detection limit is 0.2 micromol methyl paraoxon per liter.

  7. Distribution of Organophosphate Esters between the Gas and Particle Phase-Model Predictions vs Measured Data.

    PubMed

    Sühring, Roxana; Wolschke, Hendrik; Diamond, Miriam L; Jantunen, Liisa M; Scheringer, Martin

    2016-07-05

    Gas-particle partitioning is one of the key factors that affect the environmental fate of semivolatile organic chemicals. Many organophosphate esters (OPEs) have been reported to primarily partition to particles in the atmosphere. However, because of the wide range of their physicochemical properties, it is unlikely that OPEs are mainly in the particle phase "as a class". We compared gas-particle partitioning predictions for 32 OPEs made by the commonly used OECD POV and LRTP Screening Tool ("the Tool") with the partitioning models of Junge-Pankow (J-P) and Harner-Bidleman (H-B), as well as recently measured data on OPE gas-particle partitioning. The results indicate that half of the tested OPEs partition into the gas phase. Partitioning into the gas phase seems to be determined by an octanol-air partition coefficient (log KOA) < 10 and a subcooled liquid vapor pressure (log PL) > -5 (PL in Pa), as well as the total suspended particle concentration (TSP) in the sampling area. The uncertainty of the physicochemical property data of the OPEs did not change this estimate. Furthermore, the predictions by the Tool, J-P- and H-B-models agreed with recently measured OPE gas-particle partitioning.

  8. 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

  9. Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression

    SciTech Connect

    Myllymaeki, S.A. . E-mail: saanmy@utu.fi; Karjalainen, M.; Haavisto, T.E.; Toppari, J.; Paranko, J.

    2005-08-22

    Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening.

  10. Glyphosate Poisoning with Acute Pulmonary Edema

    PubMed Central

    Thakur, Darshana Sudip; Khot, Rajashree; Joshi, P. P.; Pandharipande, Madhuri; Nagpure, Keshav

    2014-01-01

    GlySH-surfactant herbicide (GlySH), one of the most commonly used herbicides worldwide, has been considered as minimally toxic to humans. However, clinical toxicologists occasionally encounter cases of severe systemic toxicity. The US Environmental Protection Agency (EPA) states that ‘GlySH’ is of relatively low oral and acute dermal toxicity. It does not have anticholinesterase effect and no organophosphate-like central nervous system (CNS) effects. The clinical features range from skin and throat irritation to hypotension and death. Severe GlySH-surfactant poisoning is manifested by gastroenteritis, respiratory disturbances, altered mental status, hypotension refractory to the treatment, renal failure, and shock.[1] GlySH intoxication has a case fatality rate 3.2–29.3%. Pulmonary toxicity and renal toxicity seem to be responsible for mortality. Metabolic acidosis, abnormal chest X-ray, arrhythmias, and elevated serum creatinine levels are useful prognostic factors for predicting GlySH mortality.[2] There is no antidote and the mainstay of treatment for systemic toxicity is decontamination and aggressive supportive therapy. We report a case of acute pulmonary edema, which is a rare but severe manifestation of oral GlySH poisoning, where patient survived with aggressive supportive therapy. PMID:25948977

  11. Acute illness associated with use of pest strips - seven U.S. States and Canada, 2000-2013.

    PubMed

    Tsai, Rebecca J; Sievert, Jennifer; Prado, Joanne; Buhl, Kaci; Stone, Dave L; Forrester, Mathias; Higgins, Shelia; Mitchell, Yvette; Schwartz, Abby; Calvert, Geoffrey M

    2014-01-17

    Dichlorvos-impregnated resin strips (DDVP pest strips) are among the few organophosphate products still available for indoor residential use. The residential uses for most other organophosphate products, including most DDVP products, were canceled because they posed unreasonable risks to children. DDVP pest strips act by inhibiting acetylcholinesterase activity in the brain and nerves of insect pests and are designed to gradually release DDVP vapor for up to 4 months. Acute illnesses in humans associated with nonlethal acute exposures usually resolve completely, but recovery is not always rapid. To assess the frequency of acute illnesses associated with DDVP pest strips, cases from 2000 through June 2013 were sought from the 12 states that participate in the Sentinel Event Notification System for Occupational Risks (SENSOR)-Pesticides Program, the National Pesticide Information Center (NPIC), and Health Canada.* A total of 31 acute DDVP pest strip-related illness cases were identified in seven U.S. states and Canada. The majority of these illnesses resulted from use of the product in commonly occupied living areas (e.g., kitchens and bedrooms), in violation of label directions. Although 26 of the 31 cases involved mild health effects of short duration, five persons had moderate health effects. Illnesses caused by excess exposure to DDVP pest strips can be reduced by educating the public about the proper usage of DDVP pest strips and with improvements in label directions.

  12. Characterisation of the organophosphate hydrolase catalytic activity of SsoPox

    PubMed Central

    Hiblot, Julien; Gotthard, Guillaume; Chabriere, Eric; Elias, Mikael

    2012-01-01

    SsoPox is a lactonase endowed with promiscuous phosphotriesterase activity isolated from Sulfolobus solfataricus that belongs to the Phosphotriesterase-Like Lactonase family. Because of its intrinsic thermal stability, SsoPox is seen as an appealing candidate as a bioscavenger for organophosphorus compounds. A comprehensive kinetic characterisation of SsoPox has been performed with various phosphotriesters (insecticides) and phosphodiesters (nerve agent analogues) as substrates. We show that SsoPox is active for a broad range of OPs and remains active under denaturing conditions. In addition, its OP hydrolase activity is highly stimulated by anionic detergent at ambient temperature and exhibits catalytic efficiencies as high as kcat/KM of 105 M−1s−1 against a nerve agent analogue. The structure of SsoPox bound to the phosphotriester fensulfothion reveals an unexpected and non-productive binding mode. This feature suggests that SsoPox's active site is sub-optimal for phosphotriester binding, which depends not only upon shape but also on localised charge of the ligand. PMID:23139857

  13. 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

  14. Orange Pomace Improves Postprandial Glycemic Responses: An Acute, Randomized, Placebo-Controlled, Double-Blind, Crossover Trial in Overweight Men

    PubMed Central

    Chen, C.-Y. Oliver; Rasmussen, Helen; Kamil, Alison; Du, Peng; Blumberg, Jeffrey B.

    2017-01-01

    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-controlled, double blind, crossover trial with 34 overweight men who consumed either a 255 g placebo (PLA), a low (35% OP (LOP)), or a high (77% (HOP)) dose OP beverage with breakfast. Blood was collected at 0, 10, 20, 30, and 45 min and at 1, 1.5, 2, 3, 4, 5, 5.5, 6, 6.5, 7, and 8 h. Lunch was consumed after the 5.5-h blood draw. OP delayed the time (Tmax1) to the maximum concentration (Cmax1) of serum glucose during the 2-h period post breakfast by ≥36% from 33 (PLA) to 45 (HOP) and 47 (LOP) min (p = 0.055 and 0.013, respectively). OP decreased post-breakfast insulin Cmax1 by ≥10% and LOP delayed the Tmax1 by 14 min, compared to PLA at 46 min (p ≤ 0.05). HOP reduced the first 2-h insulin area under concentration time curve (AUC) by 23% compared to PLA. Thus, OP diminishes postprandial glycemic responses to a high carbohydrate/fat breakfast and the second meal in overweight men. PMID:28208806

  15. Orange Pomace Improves Postprandial Glycemic Responses: An Acute, Randomized, Placebo-Controlled, Double-Blind, Crossover Trial in Overweight Men.

    PubMed

    Chen, C-Y Oliver; Rasmussen, Helen; Kamil, Alison; Du, Peng; Blumberg, Jeffrey B

    2017-02-13

    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-controlled, double blind, crossover trial with 34 overweight men who consumed either a 255 g placebo (PLA), a low (35% OP (LOP)), or a high (77% (HOP)) dose OP beverage with breakfast. Blood was collected at 0, 10, 20, 30, and 45 min and at 1, 1.5, 2, 3, 4, 5, 5.5, 6, 6.5, 7, and 8 h. Lunch was consumed after the 5.5-h blood draw. OP delayed the time (Tmax1) to the maximum concentration (Cmax1) of serum glucose during the 2-h period post breakfast by ≥36% from 33 (PLA) to 45 (HOP) and 47 (LOP) min (p = 0.055 and 0.013, respectively). OP decreased post-breakfast insulin Cmax1 by ≥10% and LOP delayed the Tmax1 by 14 min, compared to PLA at 46 min (p ≤ 0.05). HOP reduced the first 2-h insulin area under concentration time curve (AUC) by 23% compared to PLA. Thus, OP diminishes postprandial glycemic responses to a high carbohydrate/fat breakfast and the second meal in overweight men.

  16. Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study.

    PubMed Central

    Whyatt, R M; Barr, D B

    2001-01-01

    Experimental data have linked exposure to prenatal organophosphates to adverse neurocognitive sequalae. However, epidemiologic research has been hampered by lack of reliable dosimeters. Existing biomarkers reflect short-term exposure only. Measurements of pesticides in postpartum meconium may yield a longer-term dosimeter of prenatal exposure. As the initial step in biomarker validation, this research determined background levels, detection limits, and stabilities of six organophosphate metabolites in meconium: diethylphosphate (DEP), diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), dimethylphosphate (DMP), dimethylthiophosphate (DMTP), and dimethyldithiophosphate (DMDTP). Calibration curves were also constructed. The meconium was collected from 20 newborns at New York Presbyterian Hospital; analyses were undertaken at the Centers for Disease Control and Prevention (CDC). DEP was detected in 19/20 samples (range 0.8-3.2 microg/g) and DETP was detected in 20/20 (range 2.0-5.6 microg/g). DMP and DEDTP were each detected in 1/20 (at 16 and 1.8 microg/g, respectively). DMTP and DMDTP were not detected. Detection limits were comparable to or lower than those in urine; levels were similar to those seen in adult urine in population-based research. Metabolites were stable at room temperature over 12 hr. Calibration curves were linear over the range tested (0.5-400 microg/g); recoveries ranged from 18% to 66%. Using isotope dilution, recoveries of each analyte in individual samples can be corrected automatically based on the recovery of the respective stable isotope-labeled analogue, making this method fully quantitative. Results indicate that measurements of organophosphate metabolites in meconium have promise as biomarkers of prenatal exposure. Further research is needed to determine the time frame of exposure represented by pesticide levels in meconium and to evaluate the dose-response relationship. PMID:11335191

  17. Editor's Highlight: Comparative Toxicity of Organophosphate Flame Retardants and Polybrominated Diphenyl Ethers to Caenorhabditis elegans.

    PubMed

    Behl, Mamta; Rice, Julie R; Smith, Marjo V; Co, Caroll A; Bridge, Matthew F; Hsieh, Jui-Hua; Freedman, Jonathan H; Boyd, Windy A

    2016-12-01

    With the phasing-out of the polybrominated diphenyl ether (PBDE) flame retardants due to concerns regarding their potential developmental toxicity, the use of replacement compounds such as organophosphate flame retardants (OPFRs) has increased. Limited toxicity data are currently available to estimate the potential adverse health effects of the OPFRs. The toxicological effects of 4 brominated flame retardants, including 3 PBDEs and 3,3',5,5'-tetrabromobisphenol A, were compared with 6 aromatic OPFRs and 2 aliphatic OPFRs. The effects of these chemicals were determined using 3 biological endpoints in the nematode Caenorhabditis elegans (feeding, larval development, and reproduction). Because C. elegans development was previously reported to be sensitive to mitochondrial function, results were compared with those from an in vitro mitochondrial membrane permeabilization (MMP) assay. Overall 11 of the 12 flame retardants were active in 1 or more C. elegans biological endpoints, with only tris(2-chloroethyl) phosphate inactive across all endpoints including the in vitro MMP assay. For 2 of the C. elegans endpoints, at least 1 OPFR had similar toxicity to the PBDEs: triphenyl phosphate (TPHP) inhibited larval development at levels comparable to the 3 PBDEs; whereas TPHP and isopropylated phenol phosphate (IPP) affected C. elegans reproduction at levels similar to the PBDE commercial mixture, DE-71. The PBDEs reduced C. elegans feeding at lower concentrations than any OPFR. In addition, 9 of the 11 chemicals that inhibited C. elegans larval development also caused significant mitochondrial toxicity. These results suggest that some of the replacement aromatic OPFRs may have levels of toxicity comparable to PBDEs.

  18. Atmospheric transport of organophosphate pesticides from California's Central Valley to the Sierra Nevada Mountains

    USGS Publications Warehouse

    Zabik, John M.; Seiber, James N.

    1993-01-01

    Atmospheric transport of organophosphate pesticides from California's Central Valley to the Sierra Nevada mountains was assessed by collecting air- and wet-deposition samples during December, January, February, and March, 1990 to 1991. Large-scale spraying of these pesticides occurs during December and January to control insect infestations in valley orchards. Sampling sites were placed at 114- (base of the foothills), 533-, and 1920-m elevations. Samples acquired at these sites contained chlorpyrifos [phosphorothioic acid; 0,0-diethyl 0-(3,5,6-trichloro-2-pyridinyl) ester], parathion [phosphorothioic acid, 0-0-diethylo-(4-nitrophenyl) ester], diazinon {phosphorothioic acid, 0,0-diethyl 0-[6-methyl-2-(1-methylethyl)-4-pyrimidinyl] ester} diazinonoxon {phosphoric acid, 0,0-diethyl 0-[6-methyl-2-(1-methylethyl)-4-pyrimidinyl] ester}, and paraoxon [phosphoric acid, 0,0-diethyl 0-(4-nitrophenyl) ester] in both air and wet deposition samples. Air concentrations of chloropyrifos, diazinon and parathion ranged from 13 to 13 000 pg/m3 at the base of the foothills. At 533-m air concentrations were below the limit of quantification (1.4 pg/m3) to 83 pg/m3 and at 1920 m concentrations were below the limit of quantification. Concentrations in wet deposition varied with distance and elevation from the Central Valley. Rainwater concentrations at the base of the foot hills ranged from 16 to 7600 pg/mL. At 533-m rain and snow water concentrations ranged from below the limit of quantification (1.3 pg/mL) to 140 pg/mL and at 1920 m concentrations ranged from below the limit of quantification to 48 pg/mL. These findings indicate that atmospheric transport of pesticides applied in the valley to the Sierra Nevada mountains is occurring, but the levels decrease as distance and elevation increase from the valley floor.

  19. Simultaneous determination of eight metabolites of organophosphate and pyrethroid pesticides in urine.

    PubMed

    Guo, Xin Y; Sun, Li S; Huang, Meng Y; Xu, Wei L; Wang, Ying; Wang, Na

    2017-01-02

    A simultaneous method for quantifying eight metabolites of organophosphate pesticides and pyrethroid pesticides in urine samples has been established. The analytes were extracted using liquid-liquid extraction coupled with WCX solid phase extraction (SPE) cartridges. Eight metabolites were chemically derivatized before analysis using gas chromatography-tandem mass spectrometry (GC-MS-MS). The separation was performed on a HP-5MS capillary column (30 m × 0.25 mm × 0.25 µm) with temperature programming. The detection was performed under electro-spray ionization (ESI) in multiple reaction monitoring (MRM) mode. An internal standard method was used. The extraction solvent, types of SPE cartridges and eluents were optimized by comparing the sample recoveries under different conditions. The results showed that the calibration curves of the five organophosphorus pesticides metabolites were linear in the range of 0.2-200 μg/L (r(2) ≥ 0.992) and that of the three pyrethroid pesticides metabolites were linear in the range of 0.025-250 μg/L (r(2) ≥ 0.991). The limits of detection (LODs, S/N ≥ 3) and the limits of quantification (LOQs, S/N ≥ 10) of the eight metabolites were 0.008-0.833 μg/L and 0.25-2.5 μg/L, respectively. The recoveries of the eight metabolites ranged from 54.08% to 82.49%. This efficient, stable, and cost-effective method is adequate to handle the large number of samples required for surveying the exposure level of organophosphorus and pyrethroid pesticides in the general population.

  20. Intrinsic optical fiber sensor for sensing organophosphate nerve agent using the modified cladding approach

    NASA Astrophysics Data System (ADS)

    Bansal, Lalitkumar; El-Sherif, Mahmoud

    2004-03-01

    The concept of modified cladding based sensors represents the largest class of intrinsic fiber optic chemical sensors. In this design, the passive cladding of the optical fiber is replaced by an active coating, called modified cladding. The analyte in this case diffuses into the coating and induces changes in the absorbance, fluorescence, or some other spectroscopic property of the modified cladding, the coating acts as a chemo-chromic transducer and sensing takes place by intensity modulation. This design i.e. of the coating based sensors, has found enormous applicability in the realm of chemical and biochemical sensing which also includes environmental monitoring and detection of chemical warfare agents. In this paper, the development of an intrinsic fiber optic sensor for detection of organophosphate dimethyl-methyl phoshopnate (DMMP) is presented. DMMP is a chemical precursor to the nerve agent sarin. The chemo-chromic transducer material used as a modified coating on the fiber core is NDSA (Naphthalene disulphonic acid) doped polypyrrole. This coating material shows conductivity and absorbance change when exposed to DMMP. The fabrication of the sensor device is a three step process which involves (a) etching a small section of the optical fiber to expose the core, (b) coating the etched section of the optical fiber with the polymer, (c) integration of sensor components and testing. Thin film characterization is done using the UV-Vis spectrophotometer on in-situ coated films of polypyrrole on a glass substrate to check for absorbance change upon exposure to DMMP. The development procedure is presented next and encouraging results are discussed.

  1. Concentrations in air of organobromine, organochlorine and organophosphate flame retardants in Toronto, Canada

    NASA Astrophysics Data System (ADS)

    Shoeib, Mahiba; Ahrens, Lutz; Jantunen, Liisa; Harner, Tom

    2014-12-01

    Concentrations of organobromine (BFRs), organochlorine (CFRs) and organophosphate esters flame retardants and plasticizers (PFRs) in air were monitored for over one year at an urban site in Toronto, Canada during 2010-2011. The mean value for polybrominated diphenyl ethers (BDEs) (gas + particle phase) was 38 pg/m3 with BDE-47 and BDE-99 as the dominant congeners. The mean concentrations in air for ∑non-BDE (BFRs and CFRs), was 9.6 pg/m3 - about four times lower than the BDEs. The brominated FRs: TBP-AE, BTBPE, EH-TBB, BEH-TEBP and the chlorinated syn- and anti-DP were detected frequently, ranging from 87% to 96%. Highest concentrations in air among all flame retardant classes were observed for the Σ-PFRs. The yearly mean concentration in air for ΣPFRs was 2643 pg/m3 with detection frequency higher than 80%. Except for TBP-AE and b- DBE-DBCH, non-BDEs (BFRs, CFRs and PFRs) were mainly associated with the particle phase. BDE concentrations in air were positively correlated with temperature indicating that volatilization from local sources was an important factor controlling levels in air. This correlation did not hold for most BFRs, CFRs and PFRs which were mainly on particles. For these compounds, air concentrations in Toronto are likely related to emissions from point sources and advective inputs. This study highlights the importance of urban air monitoring for FRs. Urban air can be considered a sentinel for detecting changes in the use and application of FRs in commercial products.

  2. Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure.

    PubMed

    Abou-Elwafa Abdallah, Mohamed; Pawar, Gopal; Harrad, Stuart

    2016-01-15

    Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm(2), finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24h exposure. The