Clinical utility of validated gas chromatography-ion trap mass spectrometry in patients with anticholinesterase pesticides poisoning.

Intentional or unintentional intake of anticholinesterase pesticides became common due to their extensive use in agricultural and domestic purposes, resulting in numerous poisoning cases. A simple, accurate, and sensitive gas chromatography-ion trap mass spectrometry-based method for the quantification of 12 anticholinesterase pesticides (monocrotophos, dimethoate, dichlorvos, azinphos-methyl, carbofuran, chlorpyrifos, dialifos, diazinon, malathion, parathion, methidathion, and terbufos) in serum was developed, and its utility in patients with alleged pesticides poisoning was assessed. The quantification was performed using liquid-liquid extraction by toluene/chloroform (4:1,v/v) with 500 µL of serum. On column limit of detection and limit of quantification were less than 50.00 µg/L. The recovery ranged from 97.54 to 103.23%. The calibration curves were linear (R2 > 0.9937). Accuracy was found to be between - 7.1 and 7.2%. Intra-day and inter-day reproducibility was less than 17% for the spiked quality control serum samples. The level of pesticide in serum quantified by the validated method correlated with clinical signs and symptoms, pseudo-cholinesterase activity, total atropine dose, length of hospital stay, and clinical outcome in 15 patients with alleged pesticide poisoning. The validated method may be used for monitoring and prognosis in patients with pesticide poisoning and diagnosis of poisoning in forensic toxicology.

Assessment of false transmitters as treatments for nerve agent poisoning.

Nerve agents inhibit acetylcholinesterase (AChE), leading to a build-up of acetylcholine (ACh) and overstimulation at cholinergic synapses. Current post-exposure nerve agent treatment includes atropine to treat overstimulation at muscarinic synapses, a benzodiazepine anti-convulsant, and an oxime to restore the function of AChE. Aside from the oxime, the components do not act directly to reduce the overstimulation at nicotinic synapses. The false transmitters acetylmonoethylcholine (AMECh) and acetyldiethylcholine (ADECh) are analogs of ACh, synthesised similarly at synapses. AMECh and ADECh are partial agonists, with reduced activity compared to ACh, so it was hypothesised the false transmitters could reduce overstimulation. Synthetic routes to AMECh and ADECh, and their precursors, monoethylcholine (MECh) and diethylcholine (DECh), were devised, allowing them to be produced easily on a laboratory-scale. The mechanism of action of the false transmitters was investigated in vitro. AMECh acted as a partial agonist at human muscarinic (M1 and M3) and muscle-type nicotinic receptors, and ADECh was a partial agonist only at certain muscarinic subtypes. Their precursors acted as antagonists at muscle-type nicotinic, but not muscarinic receptors. Administration of MECh and DECh improved neuromuscular function in the soman-exposed guinea-pig hemi-diaphragm preparation. False transmitters may therefore help reduce nerve agent induced overstimulation at cholinergic synapses.

Effect of pesticide exposure on the cholinesterase activity of the occupationally exposed tea garden workers of northern part of West Bengal, India.

Context: Pesticide poisoning and related deaths are a global concern, but there is little information about its effect on the occupationally exposed tea garden workers of North Bengal. Objective: This study investigates the level of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the blood of the tea garden workers at risk of exposure to a mixture of pesticides. Materials and methods: The study sample consisted of pesticide exposed workers, non-exposed (control), smokers and alcoholics. AChE and BuChE activity was measured and tested for significance. Results: Results showed that AChE activity was half in the pesticide exposed individuals than controls (p≤ 0.001). BuChE activity was also significantly decreased in the pesticide exposed individuals than controls (p≤ 0.001), while AChE and BuChE activity in smokers and alcoholics were not different from that of controls. However, significantly decreased AChE and BuChE activities were recorded in pesticide exposed workers compared to smokers and alcoholics. Conclusions: The results indicated that the decrease in enzyme activities in tea garden workers was due to mixed pesticides (containing organophosphates) exposure. Age was not found to influence the enzyme activities. However, the gender had little effect on the enzyme activities but the effect was not so prominent.

One-year mortality among hospital survivors of cholinesterase inhibitor poisoning based on Taiwan National Health Insurance Research Database from 2003 to 2012.

BACKGROUND: Acute cholinesterase inhibitor (CI) poisoning, including organophosphate and carbamate poisoning, is a crucial problem in developing countries. Acute intoxication results in a cholinergic crisis, neurological symptoms, or respiratory failure. However, the short-term and long-term outcomes of CI poisoning are seldom reported. METHODS: Data from the National Health Insurance Research Database were used to investigate the outcomes after organophosphate and carbamate poisoning. Patients who were hospitalized for a first episode of acute CI poisoning between 2003 and 2012 were enrolled in this study. Outcomes of acute CI poisoning with or without mechanical ventilation were analyzed. RESULTS: Among 6832 patients with CI poisoning, 2010 developed respiratory failure requiring mechanical ventilation, and the other 4822 patients did not require mechanical ventilation. The hospital mortality rate was higher in patients requiring mechanical ventilation than in those not requiring mechanical ventilation (33.3% versus 4.7%, p < 0.0001). In patients with respiratory failure with mechanical ventilation, the patients without pneumonia had higher mortality rate than those with pneumonia. (36.0% versus 19.9%, p < 0.0001). The 1-year mortality rate the survivors of CI poisoning was 6.7%. Among 5932 survivors after cholinesterase inhibitor poisoning, the one-year mortality rate in patients with mechanical ventilation during hospitalization was higher than those without mechanical ventilation during hospitalization (11.4% versus 5.4% respectively, p < 0.0001). CONCLUSIONS: The one-year mortality rate of survivors after CI poisoning was 6.7%. Meanwhile, age, pneumonia, and mechanical ventilation may be predictive factors for the one-year mortality among the survivors after CI poisoning. Diabetes mellitus was not a risk factor for hospital mortality in patients with CI poisoning.

Clonidine as an adjuvant in the management of acute poisoning by anticholinesterase pesticides.

INTRODUCTION: Anticholinesterase pesticides are widely used in agriculture and domestic settings throughout the world, and they are responsible for great morbidity and mortality. In Egypt and other developing countries, there is a pressing need for new affordable antidotes to treat anticholinesterase pesticide poisoning. Hence, this study was conducted to evaluate the safety and effectiveness of moderate doses of clonidine in the management of adult patients with acute anticholinesterase pesticide poisoning. METHODOLOGY: This study was an open-label, phase II pilot clinical trial. Sixty patients with acute anticholinesterase pesticide poisoning gave consent to participate in the study. They were divided into 2 equal groups, with 30 patients in each group. Group I received clonidine plus the routine treatment, while group II received only the routine treatment. Patients were subjected to full history taking, and their vital and clinical data were recorded. Serum cholinesterase levels and routine laboratory investigations were measured. The different outcomes of the patients were assessed. RESULTS: The baseline characteristics of both groups were similar. Thirteen (43.3%) patients developed significant hypotension during clonidine treatment. The clinical outcomes (including mortality, need for assisted ventilation, length of hospital stay, and total doses of atropine) showed no significant differences between the two groups. CONCLUSION: The use of clonidine in acute anticholinesterase pesticide poisoning may be associated with a high incidence of hypotension requiring intervention. The clinical outcomes may not significantly improve in clonidine-treated patients.

[Characterization of pesticide exposures reported between 2006 and 2013 to a poison information center in Chile]. / Caracterización de las exposiciones a plaguicidas entre los años 2006 y 2013 reportadas al Centro de Información Toxicológica de la Pontificia Universidad Católica de Chile.

BACKGROUND: Pesticides are widely used to increase crop yields and vector control. However, both acute and chronic exposure have health consequences. There is paucity of information about the global occurrence of pesticide poisonings. AIM: To characterize the reports of pesticide exposures received by a University Poison Information Center. MATERIAL AND METHODS: All pesticide exposures reported in Chile between 2006 and 2013 were analyzed. A data-collection sheet provided by the International Programme on Chemical Safety of the World Health Organization, was used to collect information. RESULTS: In the study period, 13,181 reports were analyzed. The main age groups exposed were preschoolers and adults. Sixty one percent of exposures occurred accidentally and 24.8% were suicide attempts. Exposures to acetylcholinesterase inhibitors was reported in 29.3% of cases, to superwarfarin rodenticides in 28.5% and to pyrethroids in 24.0%. An increased risk of suicide attempts with pesticides was observed among women, when compared with men (odds ratio: 1.5; 95% confidence intervals: 1.4-1.6; p < 0.001). The risk was higher among teenage girls. CONCLUSIONS: The amount of cases under acetyl cholinesterase inhibitor exposure, the most toxic pesticides currently in use should be highlighted. Workers should be educated and all cases should be reported to take actions aiming at reducing these events.

Caracterización de las exposiciones a plaguicidas entre los años 2006 y 2013 reportadas al Centro de Información Toxicológica de la Pontificia Universidad Católica de Chile / Characterization of pesticide exposures reported between 2006 and 2013 to a poison information center in Chile

Background: Pesticides are widely used to increase crop yields and vector control. However, both acute and chronic exposure have health consequences. There is paucity of information about the global occurrence of pesticide poisonings. Aim: To characterize the reports of pesticide exposures received by a University Poison Information Center. Material and Methods: All pesticide exposures reported in Chile between 2006 and 2013 were analyzed. A data-collection sheet provided by the International Programme on Chemical Safety of the World Health Organization, was used to collect information. Results: In the study period, 13,181 reports were analyzed. The main age groups exposed were preschoolers and adults. Sixty one percent of exposures occurred accidentally and 24.8% were suicide attempts. Exposures to acetylcholinesterase inhibitors was reported in 29.3% of cases, to superwarfarin rodenticides in 28.5% and to pyrethroids in 24.0%. An increased risk of suicide attempts with pesticides was observed among women, when compared with men (odds ratio: 1.5; 95% confidence intervals: 1.4-1.6; p < 0.001). The risk was higher among teenage girls. Conclusions: The amount of cases under acetyl cholinesterase inhibitor exposure, the most toxic pesticides currently in use should be highlighted. Workers should be educated and all cases should be reported to take actions aiming at reducing these events.

[Acute poisoning with anticholinesterase carbamate pesticides: methomyl-lannate®]. / Intoxications aiguës aux pesticides anti-cholinestérasiques de type carbamate : méthomyl-lannate®.

The methomyl is increasingly involved in suicidal and autolytic attempts. Intoxication with carbamate (CM) compounds is still a frequent cause for admission in the Emergency department of the medical assistance center (MAC) in Tunis, Tunisia. The aim of this study was to describe the demographics, clinical features and hospital course of patients presenting with CM intoxication to the ED of MAC in Tunis, Tunisia. This was a retrospective study about 52 cases of acute poisoning by methomyl, compiled in the MAC from 1st January, 2009 to December 31, 2012. Intoxications were all oral, mostly intentional (33 cases: 65%) and in young patients (29 years old). Females outnumbered males by almost 2:1. The most frequent symptom was hypotension (41 cases: 80%), followed by miosis (39 cases: 75%), rhabdomyolysis (29 cases: 55%), vomiting (18 cases: 43%), bronchorrhea (14 cases: 27%), diarrhea (11 cases: 21%) and fasciculations (8 cases: 17%). Treatments included gastric lavage in 16 patients (32%), assisted ventilation in 8 cases (17%) and atropine in 44 patients (85%). Seven patients died during hospitalization. Pesticide poisoning is a significant public health problem and some preventive measures must be strictly enforced to limit this kind of intoxication.

Exposures to multiple pesticides and the risk of Hodgkin lymphoma in Canadian men.

PURPOSE: To determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. METHODS: Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case-control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Cases (n = 316) were identified through provincial cancer registries and hospital records. Controls (n = 1,506) were frequency-matched to cases by age (± 2 years) within each province and were identified through provincial health records, telephone listings, or voter lists. The Cochran-Armitage test was used to check for trends within pesticide classes. RESULTS: Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88, 95% CI 0.92-3.87) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16, 95% CI 1.02-9.29). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47, 95% CI 1.06-5.75), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. When analyses excluded proxy respondents, OR estimates strengthened in some circumstances. CONCLUSIONS: This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens. These associations should be further evaluated, specifically in relation to age at diagnosis.

The history of pyridinium oximes as nerve gas antidotes: the British contribution.

Irwin B. Wilson, working in the laboratory of David Nachmansohn at Columbia, demonstrated the ability of hydroxylamine to reactivate cholinesterase inhibited by organophosphates. Soon thereafter Wilson and Ginsburg reacted pyridine-2-aldoxime with methyl iodide to synthesize the first pyridinium aldoxime reactivator of clinical relevance, 2-PAM (pralidoxime). Independently, and at the same time, similar work was conducted in Britain at the Chemical Defence Experimental Establishment in Porton by Green leading also to the synthesis of 2-PAM and the recognition of its reactivating properties. While the American contribution is well known, the British achievements were less publicized. The present contribution attempts to shed some light on the life and work of the people who contributed to the early development of cholinesterase reactivators, the pyridinium aldoximes at Porton.

A role for solvents in the toxicity of agricultural organophosphorus pesticides.

Organophosphorus (OP) insecticide self-poisoning is responsible for about one-quarter of global suicides. Treatment focuses on the fact that OP compounds inhibit acetylcholinesterase (AChE); however, AChE-reactivating drugs do not benefit poisoned humans. We therefore studied the role of solvent coformulants in OP toxicity in a novel minipig model of agricultural OP poisoning. Gottingen minipigs were orally poisoned with clinically relevant doses of agricultural emulsifiable concentrate (EC) dimethoate, dimethoate active ingredient (AI) alone, or solvents. Cardiorespiratory physiology and neuromuscular (NMJ) function, blood AChE activity, and arterial lactate concentration were monitored for 12h to assess poisoning severity. Poisoning with agricultural dimethoate EC40, but not saline, caused respiratory arrest within 30 min, severe distributive shock and NMJ dysfunction, that was similar to human poisoning. Mean arterial lactate rose to 15.6 [SD 2.8] mM in poisoned pigs compared to 1.4 [0.4] in controls. Moderate toxicity resulted from poisoning with dimethoate AI alone, or the major solvent cyclohexanone. Combining dimethoate with cyclohexanone reproduced severe poisoning characteristic of agricultural dimethoate EC poisoning. A formulation without cyclohexanone showed less mammalian toxicity. These results indicate that solvents play a crucial role in dimethoate toxicity. Regulatory assessment of pesticide toxicity should include solvents as well as the AIs which currently dominate the assessment. Reformulation of OP insecticides to ensure that the agricultural product has lower mammalian toxicity could result in fewer deaths after suicidal ingestion and rapidly reduce global suicide rates.

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

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

Symptoms of psychological distress and suicidal ideation among banana workers with a history of poisoning by organophosphate or n-methyl carbamate pesticides.

OBJECTIVES: Neuropsychiatric disorders and increased suicide rates have been associated with exposure to cholinesterase inhibiting organophosphates. This study examined symptoms of psychological distress, including suicidal ideation, among banana workers in Costa Rica previously exposed to a cholinesterase inhibiting pesticide. METHODS: 78 workers who had received medical attention 1-3 years previously for occupational pesticide poisoning were recruited: 54 had been exposed to organophosphate, 24 to carbamate, and 43 and 35, respectively, had single and multiple poisoning episodes with a cholinesterase inhibitor. Referents were 130 non-poisoned workers randomly selected from company payrolls. Psychological distress symptoms during the month prior to interview were obtained using the Brief Symptom Inventory (BSI), which has a general severity index and nine subscale scores. Differences in abnormal BSI scores (T score≥63) were assessed through multivariate logistic regression for all poisoned and for subcategories of poisoned as compared to non-poisoned workers. RESULTS: Organophosphate poisoned workers reported significantly more symptoms than non-poisoned on all but one symptom dimension. Significant trends of increasing symptoms with increasing number of previous poisonings were seen for somatisation, obsessive-compulsiveness, interpersonal sensitivity, depression and anxiety. Carbamate poisoned workers only had increased scores for somatisation. The ORs for suicidal thoughts were: all poisoned 3.58 (95% CI 1.45 to 8.84); organophosphate poisoned 3.72 (1.41 to 9.81); carbamate poisoned 2.57 (0.73 to 9.81); and 2.65 and 4.98, respectively for 1 and ≥2 poisonings (trend p=0.01). CONCLUSIONS: This cross-sectional study showed a relationship between acute occupational poisoning with organophosphates and psychological distress including suicidal ideation. Stronger designs are needed to address causality.

Protective effects of Y-27632 on acute dichlorvos poisoning in rats.

Anticholinesterase poisoning is an important health problem in developing countries, and understanding of its underlying mechanisms is essential for the effective treatment. This study is designed to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced cardiac toxicity and mortality in rats. Rats were randomly divided into 4 groups: control (corn oil), dichlorvos (30 mg/kg intraperitoneally), and 1- and 10-mg/kg Y-27632 + dichlorvos groups. After 6 hours of intraperitoneal injection, venous blood and cardiac samples were obtained, biochemical or immunohistochemical analyses were performed, and the intensity of muscle fasciculation was recorded. Serum cholinesterase activities were suppressed with dichlorvos, and these reductions were inhibited with Y-27632 pretreatment. Serum creatine kinase, creatine kinase-MB activities, and myoglobin and N-terminal probrain natriuretic peptide concentrations were not markedly affected with poisoning or Y-27632. Although serum nitric oxide concentrations did not change with dichlorvos, cardiac nitric oxide levels were markedly increased with Y-27632 pretreatment. Cardiac glutathione levels also increased with 1 mg/kg Y-27632. There was no staining for apoptosis, and immunohistochemical analyses of inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Both doses of Y-27632 abolished mortality in rats with acute dichlorvos exposure (100% survival). These results show that administration of Rho-kinase inhibitor can produce protective effects against dichlorvos intoxication in rats. These findings may provide new possibilities for the treatment of organophosphate poisoning.

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

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

Chronic exposures to cholinesterase-inhibiting pesticides adversely affect respiratory health of agricultural workers in India.

OBJECTIVE: The impact of long term exposure to cholinesterase (ChE)-inhibiting organophosphate (OP) and carbamate (C) pesticides on the respiratory health of agricultural workers in India was investigated. METHODS: Three hundred and seventy-six nonsmoking agricultural workers (median age 41 yr) from eastern India who sprayed OP and C pesticides in the field and 348 age- and sex-matched control subjects with non-agricultural occupations from the same locality were enrolled. Prevalence of respiratory symptoms was obtained by questionnaire survey, and pulmonary function tests were carried out by spirometry. Chronic obstructive pulmonary disease (COPD) was diagnosed by the Global Obstructive Lung Disease (GOLD) criteria, and erythrocyte acetylcholinesterase (AChE) was measured by the Ellman method. RESULTS: Agricultural workers had greater prevalences of upper and lower respiratory symptoms, and appreciable reduction in spirometric measurements. Overall, lung function reduction was noted in 48.9% of agricultural workers compared with 22.7% of control, and a restrictive type of deficit was predominant. COPD was diagnosed in 10.9% of agricultural workers compared with 3.4% of controls (p<0.05 in chi(2) test), and the severity of the disease was greater in agricultural workers. Red blood cell (RBC) AChE was lowered by 34.2% in agricultural workers, and the fall in AChE level was positively associated with respiratory symptoms, lung function decrement and COPD after controlling for education and income as potential confounders. CONCLUSIONS: Long-term exposure to cholinesterase-inhibiting agricultural pesticides currently in use in India is associated with a reduction in lung function, COPD and a rise in respiratory symptoms.

Medical treatment of acute poisoning with organophosphorus and carbamate pesticides.

Organophosphorus compounds (OPs) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OP can be fatal and death is usually caused by respiratory failure. The mechanism of OP poisoning involves inhibition of acetylcholinesterase (AChE) leading to inactivation of the enzyme which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the nervous systems. During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with OP. They act by reactivation of AChE inhibited by OP. However, they differ in their activity in poisoning with pesticides and warfare nerve agents and there is still no universal broad-spectrum oxime capable of protecting against all known OP. In spite of enormous efforts devoted to development of new pyridinium oximes as potential antidotes against poisoning with OP only four compounds so far have found its application in human medicine. Presently, a combination of an antimuscarinic agent, e.g. atropine, AChE reactivator such as one of the recommended pyridinium oximes (pralidoxime, trimedoxime, obidoxime and HI-6) and diazepam are used for the treatment of OP poisoning in humans. In this article the available data related to medical treatment of poisoning with OP pesticides are reviewed and the current recommendations are presented.

Electrocardiographic findings of acute organophosphate poisoning.

In this study, we evaluated 85 patients who presented to our Emergency Department with organophosphate (OP) poisoning and discuss their associated electrocardiographic (ECG) abnormalities. Over a period of 3 years, 85 patients with OP poisoning were included in this retrospective study. ECG analysis included the rate, rhythm, ST-T abnormalities, conduction defects, and measurement of PR and QT intervals. The mean age was 32.2 +/- 14.9 years. Sixty percent of the patients were female. The mean corrected QT interval (QTc interval) was 0.435 +/- 0.052 s. Prolongation of the QTc interval (55.5%) was the most common ECG abnormality, followed by sinus tachycardia (31.8%). Elevation of the ST segment and low amplitude T waves were seen in 15 cases (17.6%). Patients with OP poisoning might reveal ECG abnormalities such as QTc interval prolongation or non-specific ST-T changes. QTc interval prolongation cannot be used as a unique predictive factor in determining short-term prognosis in OP poisoning. We found no clear relation between OP poisoning-related malignant ventricular dysrhythmia and QTc interval.

Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged mouse brain areas.

Gliotic scar formation and angiogenesis are two biological events involved in the tissue reparative process generally occurring in the brain after mechanically induced injury, ischemia or cerebral tumor development. For the first time, in this study, neo-vascularization and glial scar formation were investigated in the brain of soman-poisoned mice over a 3-month period after nerve agent exposure (1.2 LD50 of soman). Using anti-claudin-5 and anti-vascular endothelial growth factor (VEGF) immunostaining techniques on brain sections, blood vessels were quantified and VEGF expression was verified to appraise the level of neo-angiogenesis induced in damaged brain areas. Furthermore, glial scar formation and neuropathology were estimated over time in the same injured brain regions by anti-glial fibrillary acidic protein (GFAP) immunohistochemistry and hemalun-phloxin (H&P) dye staining, respectively. VEGF over-expression was noticed on post-soman day 3 in lesioned areas such as the hippocampal CA1 field and amygdala. This was followed by an increase in the quantity of mature blood vessels, 3 months after soman poisoning, in the same brain areas. On the other hand, massive astroglial cell activation was demonstrated on post-soman day 8. Reactive astroglial cells were located only in damaged cerebral regions where H&P-stained eosinophilic neurons were found. For longer experimental times, astroglial response slowly decreased overtime but remained detectable on post-soman day 90 in some discrete brain regions (i.e. CA1 field and amygdala) evidencing the formation of a glial scar. In this study, we discuss the key role of VEGF in the angiogenic process and in the glial or neuronal response induced by soman poisoning.