Blood Cholinesterase Activity Research Articles

<strong><span lang="EN-GB">Protective role of <em>Ipomoea aquatica</em> Forsk. crude extract on rat tissues in the presence of acephate and carbofuran by histopathology and cytometric determination</span></strong>

Ipomoea aquatica Forsk., commonly called water spinach ( ‘kalmi’ in Bengali) is an underexploited local green leafy vegetable having enormous scope as a cheap antioxidant source. The study explores the ameliorative effect of aqueous I. aquatica extract (IAE) in acephate and carbofuran treated Wistar male rats. Aqueous IAE (@ 20 mg/kg body wt.), administered to rats treated with organophosphate acephate (@ 30 mg/kg body wt.) and carbamate carbofuran (@ 0.1 mg /kg body wt.), attenuated the cholinesterase activity in brain, liver and cellular blood and reformed the histological perturbations in the brain cortex as well as the kidney anomalies, to a good extent. The IAE also upregulated the NF-E2-related factor-2 (Nrf-2) and MnSOD gene expression against pesticide toxicity. Hence, results of the present study intervenes into a new approach of justifying the deleterious side effects of pesticides that are commonly used, and how green leafy vegetables can help ameliorate those harmful effects.

Soman-induced toxicity, cholinesterase inhibition and neuropathology in adult male Göttingen minipigs.

Animal models are essential for evaluating the toxicity of chemical warfare nerve agents (CWNAs) to extrapolate to human risk and are necessary to evaluate the efficacy of medical countermeasures. The Göttingen minipig is increasingly used for toxicological studies because it has anatomical and physiological characteristics that are similar to those of humans. Our objective was to determine whether the minipig would be a useful large animal model to evaluate the toxic effects of soman (GD). We determined the intramuscular (IM) median lethal dose (LD50) of GD in adult male Göttingen minipigs using an up-and-down dosing method. In addition to lethality estimates, we characterized the observable signs of toxicity, blood and tissue cholinesterase (ChE) activity and brain pathology following GD exposure. The 24 h LD50 of GD was estimated to be 4.7 μg/kg, with 95 % confidence limits of 3.6 and 6.3 μg/kg. As anticipated, GD inhibited ChE activity in blood and several tissues. Neurohistopathological analysis showed neurodegeneration and neuroinflammation in survivors exposed to 4.7 μg/kg of GD, including in the primary visual cortex and various thalamic nuclei. These findings suggest that the minipig will be a useful large animal model for assessing drugs to mitigate neuropathological effects of exposure to CWNAs.

Decrease in Cellular Nanovesicles Concentration in Blood of Athletes More Than 15 Hours After Marathon.

IntroductionCellular nanovesicles (CNVs), that are shed from cells, have been recognized as promising indicators of health status. We analyzed the effect of long-distance running on concentration of CNVs, along with some standard blood parameters, in 27 athletes two days before and >15 hours after physical effort.MethodsCNVs were isolated by repetitive centrifugation and washing of samples, and assessed by flow cytometry. Cholinesterase (ChE) and glutathione S-transferase (GST) activity were measured spectrophotometrically. Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were measured using enzyme-linked immunosorbent assay (ELISA). C-reactive protein (CRP) was measured with immunoturbidimetric determination and lipidogram parameters were measured by enzymatic colorimetric assay. Flow cytometry was used for blood cell count and mean platelet volume (MPV) measurement.ResultsMore than 15 hours after physical effort a decrease was found in CNVs’ concentration in isolates from blood (46%; p<0.05), in ChE activity in whole blood (47%; p<0.001), in plasma (34%; p<0.01), and in erythrocyte suspension (54%; p<0.001), as well as in GST activity in erythrocyte suspension (16%; p<0.01) and in IL-6 concentration in plasma (63%; p<0.05). We found no change in GST activity in plasma and in TNF-α concentration in plasma. Correlations (>0.8; p<0.001) between CNVs’ concentration and ChE activity, and GST activity, respectively, in erythrocyte suspension were found.ConclusionWe found that >15 hours post-physical effort, CNVs’ concentration was below the initial value, concomitant with other measured parameters: ChE and GST activity as well as IL-6 concentration, indicating a favorable effect of physical effort on health status. CNVs’ concentration and ChE activity in isolates from peripheral blood proved to have potential as indicators of the response of the human body to inflammation after physical effort. Physical activity should be considered as an important factor in preparation of subjects for blood sampling in procedures focusing on CNV-containing diagnostic and therapeutic compounds.

The Cholinergic Profile as a Target for Rational Therapy of Central Nervous System Diseases and Injuries

Objective. To conduct a comparative analysis of the clinical efficacy of cholinergic drugs and acetylcholinesterase inhibitors and their combinations in the complex therapy of cerebrovascular pathology and the sequelae of closed craniocerebral trauma (cCCT) using clinical, instrumented, and laboratory follow-up investigations. Materials and methods. A total of 90 patients with cerebrovascular pathology (chronic cerebral ischemia grade 2 (I67; 45 patients) and the sequelae of cCCT (T90; 45 patients) were studied. Groups were divided into three subgroups each of 15 patients. Complex treatment included basal and specific therapy: subgroup 1 received the drug Neuromidin, group 2 received Gliatilin, and group 3 received Neuromidin plus Gliatilin. Treatment duration was two months. All patients underwent complex clinical, neurophysiological, and laboratory investigations before treatment and at one and two months from treatment initiation: plasma cholinesterase activity was estimated, patients were tested on the Mini Mental State Examination (MMSE) and the Hamilton scale, and patients underwent transcranial magnetic stimulation with assessment of the central motor conduction time and evaluation of somatosensory evoked potentials with determination of the central afferent conduction time. Results. Before treatment, a strong positive correlational relationship was found between patients’ age and serum cholinesterase activity (Rs = 0.77; p = 0.0001). On the background of treatment, all study parameters showed significant (p < 0.05) improvements with the exception of the MMSE, which showed only a trend to improvement) in subgroups 1 and 3 of each group as compared with values obtained in subgroups 2 of the corresponding groups. In addition, at two months from treatment initiation, there were significant decreases in serum cholinesterase activity in patients of subgroups 1 and 2. Conclusions. Assessment of deviations in the “cholinergic profile” (blood cholinesterase activity) in patients with cerebral pathology and the strategy of using cholinergic drugs and acetylcholinesterase inhibitors and their combination to correct psychoneurological disorders is among the most important directions in optimizing the combined treatment of patients of this category.

Faktor Yang Berhubungan dengan Kejadian Keracunan Pestisida Pada Petani Sayur dan Palawija di Desa Selat Kecamatan Pemayung Kabupaten Batang Hari Tahun 2018

Pesticide is toxic and harmful materials, this pesticide can cause either positive or negative impact for the prosperity of the human beings and environment. The negative impact wiil cause directly various problems to our health. Pesticide poisoning can be identified by examining blood cholinesterase activity. The aim of this research is to identify factors that related to pesticide exposure to the level of blood cholinesterase of farmers that spray non-staple food crops at Selat Village of Pemayung Sub-district of Batang Hari Ditrict. This research method is a quantitative research with cross sectional design. Independent variables in this research are knowledge concening pesticide, protective clothes, sprying in line with wind direction, while the dependent variable was the farmers. The population was all non-staple food crops farmers at at Selat Village of Pemayung Sub-district of Batang Hari Ditrict. The samples were 30 people. The results of the research by applying statistic test, there was a relation of knowledge to pesticide poisoning with P value = 0.019, the use of protective clothes with P value = 0.024 and spraying in line with wind direction with P value = 0.000. The research shows that non-staple food crops farmers at Selat Village had pesticide poisoning of 80.0%. In order to prevent pesticide poisonong, it is recommended that the farmers should improve their knowledge regarding pesticide, while spraying the pesticide, farmers should wear complete protective clothes properly and make sure to follow the wind direction while spraying.

The pro-convulsant effects of diazinon low dose in male rats under amygdala kindling

Organophosphates can damage the brain in systemic intoxication. In this study, the effects of a minimum toxic dose (MTD) of diazinon (DZ) on amygdala afterdischarge threshold (ADT), kindling acquisition and kindled seizure parameters were evaluated. Intact male rats were stereotactically implanted with a tripolar and two monopolar electrodes in the amygdala and dura respectively. After recovery, animals received daily either, olive oil (control), 15 or 30 mg/kg (MTD) of DZ intraperitoneally, and ADT, afterdischarge duration (ADD) at each stage (S1 to S5) of kindling and number of trials for kindling acquisition were determined daily. Also, the effect of DZ on stage 4 latency (S4L), ADD, stage 5 duration (S5D) and the activity of the red blood cholinesterase (ChE) were evaluated. The ADT was lower and the ADD was longer significantly in DZ treated group in comparison to control (p < 0.01) and the number of trials to reach each stage of kindling acquisition was reduced (p < 0.001). The total amount of ADDs during the kindling procedure increased significantly 5 days after DZ treatment. While the S4L was reduced, the S5D increased significantly after DZ treatment. The ChE activity was inhibited significantly after 20 min of DZ treatment and continued till 24 h (p < 0.01). Data indicate that even half of the MTD of DZ could increase the sensitivity and excitability of the CNS to the epileptic activity at least via reduction of stimulation threshold and AD prolongation. Furthermore, repeated exposure to the low concentrations of organophosphates may be pro-convulsant and should be restricted.

The behavior of Pesticide Usage and Risk of Health Disorders in Vegetable Farmers

The study aims to describe the behavior of pesticide usage and its effect on farmer health. Pesticide usage behavior includes indicators of storage behavior and application action. The farmers’ health is observed in the activity of cholinesterase blood and the symptoms of the disease. The study has occurred in March-August 2017 involving 60 vegetable farmers in Tinggimoncong District of Gowa Regency, South Sulawesi Province. Blood cholinesterase activity was measured by taking farmers’ blood samples. The results showed that farmers showed erroneous behavior in the use of pesticides such as throwing pesticide packaging in an unsafe place and not using the right personal protective equipment. Farmers are at risk for health problems due to mild levels of poisoning.

Inhibition of cholinesterases following percutaneous intoxication with V agents in rats

Female Wistar rats were percutaneously (p.c.) intoxicated (1xLD50) with VX and its two derivatives differing in their substitution on nitrogen (diethyl- and dibutyl- derivatives). Blood cholinesterase activity was continuously monitored; 100 min after the intoxication (or after death), acetylcholinesterase (AChE) activity was determined in diaphragm and brain parts (pontomedullar area – PM, frontal cortex – FC, and basal ganglia – BG). Blood ChE activity remains unchanged at very short interval (5 min) after VX administration; this interval was prolonged for diethyl- and dibutyl derivatives. AChE activity was decreased to 20–30% of control values in diaphragm, then in FC (60–70%) and PM (54–74%). AChE activity in BG was relatively resistant (cca 80%). When the AChE activity was compared for all three agents in relationship to survival (11 animals) or death (7 animals), significant differences between the activities in survived (32%) and died (13%) rats were demonstrated in diaphragm but not in the blood. This tendency (higher AChE activity in survived animals) was also observed in PM and FC, however, not statistically significant. It is concluded that both parts of the molecule – substitution on nitrogen atom and the rest of agent molecule (phosphorus head) probably influence penetration through the skin and simultaneously AChE inhibition. As hypothesis, AChE activity in diaphragm could be important for survival or death in case of acute p.c. intoxication with these types of V agents.

DNA Damaging Effects, Oxidative Stress Responses and Cholinesterase Activity in Blood and Brain of Wistar Rats Exposed to Δ9-Tetrahydrocannabinol.

Currently we are faced with an ever-growing use of Δ9-tetrahydrocannabinol (THC) preparations, often used as supportive therapies for various malignancies and neurological disorders. As some of illegally distributed forms of such preparations, like cannabis oils and butane hash oil, might contain over 80% of THC, their consumers can become intoxicated or experience various detrimental effects. This fact motivated us for the assessments of THC toxicity in vivo on a Wistar rat model, at a daily oral dose of 7 mg/kg which is comparable to those found in illicit preparations. The main objective of the present study was to establish the magnitude and dynamics of DNA breakage associated with THC exposure in white blood and brain cells of treated rats using the alkaline comet assay. The extent of oxidative stress after acute 24 h exposure to THC was also determined as well as changes in activities of plasma and brain cholinesterases (ChE) in THC-treated and control rats. The DNA of brain cells was more prone to breakage after THC treatment compared to DNA in white blood cells. Even though DNA damage quantified by the alkaline comet assay is subject to repair, its elevated level detected in the brain cells of THC-treated rats was reason for concern. Since neurons do not proliferate, increased levels of DNA damage present threats to these cells in terms of both viability and genome stability, while inefficient DNA repair might lead to their progressive loss. The present study contributes to existing knowledge with evidence that acute exposure to a high THC dose led to low-level DNA damage in white blood cells and brain cells of rats and induced oxidative stress in brain, but did not disturb ChE activities.

Exposure of chlorpyrifos in toddlers living in an agricultural area in Sakon Nakhon province, North-East Thailand

Purpose Children living in agricultural areas are exposed to pesticides in their living areas and through activities of daily living. These exposures may lead to adverse health effects. The purpose of this paper is to investigate household environmental and behavioural factors associated with chlorpyrifos exposure and resultant adverse health effects in children living in an agricultural community. Design/methodology/approach A cross-sectional study was conducted including 65 toddlers (age of 12–36 months) and their parents were face-to-face interviewed from January to February 2016. Toddler’s hands and feet, toys and floors were wiped for chlorpyrifos residue analysis. The wipes were extracted and analysed by gas chromatography with a flame photometric detector, and blood cholinesterase activity was measured by the EQM Test-mate (model 400). Findings The average age (± standard deviation) of children was 19.9 (±5.9) months. Chlorpyrifos detections were 61.5 per cent (hands), 57.1 per cent (toys), 53.8 per cent (floors) and 30.8 per cent (feet). The highest chlorpyrifos residue concentration was detected on toy surface (3.022 µg/m2). Chlorpyrifos residues on hands and feet were positively correlated with concentrations on floors and toys (Spearman’s ρ, p&lt;0.01). Multiple linear regression analysis revealed that more frequent hand washing (β=−0.236, p=0.067) and showering (β=−0.240, p=0.056) was negatively associated with chlorpyrifos residue on children’s body. House cleaning frequency was significantly associated with an increase in haemoglobin-adjusted erythrocyte cholinesterase (β=0.251, p&lt;0.05). Originality/value Chlorpyrifos exposures found in the children household area through their activities and behaviours can cause several adverse health effects. The circumstances associated with chlorpyrifos exposure should be mitigated and reduced to improve the household environment of children living agricultural areas.

Agroquímicos organofosforados y su potencial daño en la salud de trabajadores agrícolas del campo sonorense

El uso de agroquímicos es necesario para mantener el rendimiento promedio de los cultivos. Sin embargo, los efectos causados en los trabajadores agrícolas representan un problema de salud. La determinación de la actividad de la colinesterasa en la sangre es un valioso indicador de exposición a agroquímicos organofosforados. Con base en lo anterior, se explora la posibilidad de intoxicaciones agudas grado 1 y se determinan los valores de acetilcolinesterasa en 25 personas que laboran en actividades agrícolas y en 5 como muestra control. De la población estudiada, 86% presentó valores normales de la actividad de la colinesterasa. No obstante, los resultados sirven como indicadores biológicos de intoxicación y son importantes para el seguimiento y detección de los efectos tóxicos producidos.

FAKTOR-FAKTOR YANG BERHUBUNGAN DENGAN TINGKAT KERACUNAN PESTISIDA PADA TENAGA PENJUAL PESTISIDA

The purpose of this study to determine the risk factors that have a relation to the rate of pesticide poisoning on the seller / entrepreneur / dealers (distributors).&#x0D; This study is a survey with a cross-sectional approach. Subjects were all salespeople pesticides in Bengkulu city by 52 people (total sampling). The dependent variable is the rate of pesticide poisoning, while the independent variable is the length of service, knowledge, attitudes, practices and use of protective equipment. Statistical analysis using Chi Square followed Logistic Regression with SPSS significance level (p &lt;0.05).&#x0D; Based on the results of blood cholinesterase activity of 52 subjects, the majority were poisoned as many as 41 people (78.85%), and normal as many as 11 people (21.15%). Chi Square statistical test results show, there are several risk factors associated namely, knowledge (p = 0.000), attitude (p = 0.019), practice (p = 0.040), and the use of personal protective equipment (p = 0.001), whereas the test results Multifariate statistics using Logistic Regression, of bebarapa related factors turned out to be only 2 (two) were significantly associated, namely knowledge (p = 0.006 to OR = 25.896) and the use of personal protective equipment (p = 0.018 to OR = 9.873).

Efficacy of antidotes and their combinations in the treatment of acute carbamate poisoning in rats

BackgroundPhysostigmine and its analogues neostigmine, pyridostigmine and rivastigmine are carbamates nowadays used in many indications, including antidotal effects against antimuscarinic poisonings, reversal of competitive neuromuscular block, myasthenia gravis, Alzheimer’s disease and prophylaxis against nerve agent intoxications. Use of these medicinal carbamates, but also of carbamate insecticides, created need for research into the potential and mechanisms of action of several antidotes against carbamate poisonings, including anticholinergics and oximes. AimThe goal of this experimental study was to ascertain the life-preserving potential of anticholinergics atropine, hexamethonium and d-tubocurarine, oxime HI-6 and their combinations in rats poisoned with physostigmine or pyridostigmine. Materials and methodsExperiments were performed in Wistar rats. Carbamates were injected subcutaneously (sc) and antidotes intramuscularly (im). Median lethal dose (LD50) in animals treated with antidotes were compared to the ones in saline-treated rats and protective ratios (PRs) were calculated. Atropine (5, 10 and 20 mg/kg), hexamethonium (5, 10 and 20 mg/kg), d-tubocurarine (0.005, 0.010 and 0.020 mg/kg) and oxime HI-6 (25, 50 and 100 mg/kg) were used as monotherapies and in dual combinations, where atropine was the obligatory antidote. Biochemical experiments consisted in measuring of the cholinesterase activities in brain, whole blood and diaphragm in rats 5, 15, 30, 60, 120 and 240 min after poisoning with 0.8 LD50 of physostigmine or pyridostigmine. ResultsAll the tested antidotes assured some degree of protection against the two carbamates. Atropine and hexamethonium produced better protection in physostigmine-poisoned rats, while d-tubocurarine and HI-6 were more efficacious in pyridostigmine-intoxicated animals. Oxime HI-6 50 mg/kg reactivated acetylcholinesterase (AChE) in brain inhibited by physostigmine and in diaphragm inhibited by pyridostigmine. ConclusionsMechanism of physostigmine-induced lethal effect is predominantly central and it involves inhibition of brain AChE, while pyridostigmine produces the same effect exclusively outside the central nervous system, by inhibiting AChE in the respiratory muscles. As a consequence, increasing doses of atropine and their combination with hexamethonium assure excellent protection against physostigmine toxicity, while the best protection against pyridostigmine is provided by a strictly peripherally acting antinicotinic d-tubocurarine and bispyridinium oxime HI-6. The oxime acts as antidote against physostigmine and pyridostigmine poisoning by reactivating AChE in the brain and diaphragm, respectively.

Association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed workers

Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group (P < 0.001). Multivariate analysis indicates that exposure group (b = − 1.016, P < 0.001), agender (b = 0.365, P < 0.001), drinking (b = 0.271, P = 0.004) and TERF1rs3863242 (b = − 0.368, P = 0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate.

Factors associated with health effects from occupational exposure to pesticide residues among greengrocers in fresh market, Bangkok, Thailand

ABSTRACTGreengrocers are occupationally exposed to pesticide residues (PRs) on vegetables via dermal contact, especially organophosphates (OPs). The study's aim was to explore health effects from exposure to PRs. Eighty five vegetable vendors at a large fresh market in Bangkok were tested blood cholinesterase activity by the Test-mate ChE Kit (Model 400). The average acetylcholinesterase (AChE) and plasma cholinesterase (PChE) levels were 3.33 ± 0.66 U/ml and 2.06 ± 0.46 U/ml, respectively. The subjective symptoms were skin rash/itching, fatigue/tiredness, eye irritation/blurred vision, headache, and excessive sweating. Multiple linear regression analysis showed a positively significant association between scores of practices regarding exposure to PRs and AChE levels, and a negatively significant relationship between OP residues on hands and PChE levels (p-value < 0.05). Binary logistic regression analysis revealed that either AChE or PChE was significantly associated with eye symptoms and neuromuscular symptoms (p-value < 0.05). A statistically significant association between low score of dermal practice and having skin symptoms was found. Exposure to PRs by hand contact and consumption with poor hygiene habits can pose health problems among greengrocers. The findings emphasized that good personal hygiene practices such as wearing gloves and washing hands can prevent and reduce the health effects from exposure to PRs.

Interaction between polymorphisms in cell-cycle genes and environmental factors in regulating cholinesterase activity in people with exposure to omethoate.

Cholinesterase activity (ChA), the effective biomarker for organophosphate pesticide exposure, is possibly affected by single nucleotide polymorphisms (SNPs) in cell-cycle-related genes. One hundred and eighty workers with long-term exposure to omethoate and 115 healthy controls were recruited to explore the gene–gene and gene–environment interactions. The acetylthiocholine and dithio-bis-(nitrobenzoic acid) method was used to detect the cholinesterase activities in whole blood, erythrocytes and plasma. Genetic polymorphisms were determined by the PCR-RFLP and direct PCR electrophoresis methods. Statistical results showed that the cholinesterase activities of whole blood, erythrocytes and plasma in the exposure group were significantly lower than those in the control group (p < 0.001), and erythrocyte cholinesterase activities were associated with gender, smoking and drinking in the exposure group (p < 0.05). Single-locus analyses showed that there is a statistically significant difference in the ChA among the genotypes CC, CA and AA of the p21 rs1801270 locus in the control group (p = 0.033), but not in the exposure group. A significant interaction between genes and environmental factors (i.e. p53, p21, mdm2, gender, smoking and drinking) affecting ChA was found through a generalized multifactor dimensionality reduction analysis. These obtained markers will be useful in further marker-assisted selection in workers with exposure to omethoate.

SUSPECTED CARBARYL TOXICITY IN A CAPTIVE COLONY OF STRAW-COLORED FRUIT BATS ( EIDOLON HELVUM).

Carbaryl was the first carbamate insecticide produced and remains the most widely used due to its perceived low level of toxicity in nontarget species. This report describes the management and evaluation of a group of straw-colored fruit bats, Eidolon helvum, that were exposed to carbaryl. Cholinesterase activity of blood, retina, and brain was evaluated to further investigate whether carbaryl was the causative agent. Decreased whole blood and retinal cholinesterase activity coupled with the response to atropine suggests that the cause of the clinical signs in this bat colony was due to carbaryl exposure. Whole blood and retinal tissue may be the best samples for confirming carbamate exposure in this species.

Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats.

VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure. Characterization of such a threshold is crucial for dealing with unresolved operative dilemmas such as when it is safe enough to resettle a population that has been evacuated from a VX-contaminated area. Rats, continuously exposed to various doses of VX (0.225-45µg/kg/day) for 4weeks via implanted mini-osmotic pumps, showed a dose-dependent and continuous decrease in ChE activity in whole blood, brain and muscles, ranging between 20 and 100%. Exposure to 13.5µg/kg/day led to a stable low ChE activity level (~20%), accompanied by transient and negligible electrocorticogram spectral power transformations, especially in the theta and alpha brain wave frequencies, and a significant decrease in total brain M2 receptor density. These changes were neither accompanied by observable signs of intoxication nor by changes in motor function, circadian rhythm or TSPO level (a reliable marker of brain damage). Following exposure to lower doses of 2.25 and 0.225µg/kg/day, the only change measured was a reduction in ChE activity of 60 and 20%, respectively. Based on these results, we delineate ChE inhibition as the physiological measure most susceptible to alterations following prolonged VX exposure, and determine for the first time the threshold sub-acute VX dose for minimal physiological effects (up to 20% reduction in ChE activity) in the rat as 0.225µg/kg/day.

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

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

Factors that contribute to insecticide poisoning among immigrant agricultural workers in Thailand.

There has been a strong increase in the international movement of workers during the last few decades. As Thailand's economy has rapidly developed during the past 20years, it has attracted growing numbers of laborers from the bordering countries of Myanmar, Lao PDR, and Cambodia. Numbers of migrant workers in Thai agriculture have risen to the extent that the sector's continued growth has become increasingly dependent on migrant workers. The purpose of this study was to explore the factors that contribute to the development of symptoms of insecticide poisoning among immigrant agricultural workers in the eastern region of Thailand. Data were collected via interviews (N=891), and the levels of cholinesterase activity in the workers' blood were tested using reactive test strips. Only 4.4% of the workers had normal levels of cholinesterase activity and 75.1% had levels that were abnormal. Regarding factors that affect gastrointestinal symptoms of poisoning, being aged 45 to 50 increased the risk of developing gastrointestinal symptoms (odds ratio (OR): 2.51; 95% CI: 1.41-4.46), as did using a backpack spraying technique (OR: 3.74; 95% CI: 2.16-6.49) and having only moderate levels of self-protection behavior while spraying the insecticides (OR: 2.23; 95% CI: 1.16-4.29). Having an at risk level of cholinesterase activity increased the risk of gastrointestinal symptoms (OR: 3.25; 95% CI: 1.05-10.04) and the risk of respiratory symptoms (OR: 2.75; 95% CI: 1.17-6.44). It is recommended that insecticide self-protection measures should be promoted and health monitoring should be implemented for migrant workers affected by high-risk insecticide use.