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Introduction: Organophosphorus compounds are pesticides commonly used for agricultural purposes. However, by nature they are poisonous, and administration either accidental or intentional is a medical emergency requiring prompt evaluation and treatment, and can even lead to death. In addition due to the ease of their availability, they are commonly used for self-harm/suicidal purposes. Many of the patients are initially managed at primary or secondary healthcare setups before being referred to tertiary care hospitals. The purpose of our study is to find a prognostic marker in the initial blood work of these patients. Materials and Methods: A total of 46 patients were included in this retrospective cross-sectional survey conducted at the Department of Emergency Medicine, Holy Family Hospital, Rawalpindi. Data were collected from patient files using specific questionnaires. Outcomes were defined in terms of Emergency Department disposition. Data were analysed using SPSS v25. A univariate analysis, followed by Spearman's Correlation was used. Results: Patients with a higher WBC to Platelet ratio had worse outcomes. The Spearman's rho correlation coefficient was calculated and a moderately strong correlation (rho = .458, p < .001) was found. Conclusion: WBC to Platelet ratio is a hematological parameter determined to be most strongly correlated with adverse outcomes in Organophosphate Poisoning. It has a statistically significant stronger correlation than the WBC count alone. However, further extensive and focused studies are needed to corroborate these findings and substantiate them as a definite marker of prognostic significance. [ABSTRACT FROM AUTHOR]

BackgroundExposures to cholinesterase inhibitor pesticides (e.g. organophosphates) have been associated with children's neurobehavioral alterations, including attention deficit and impulsivity. Animal studies have observed transient alterations in neurobehavioral performance in relation to cholinesterase inhibitor pesticide exposures; however, limited evidence exists regarding transient effects in humans.MethodsWe estimated the associations between neurobehavioral performance and time after Mother's Day flower harvest (the end of a heightened pesticide usage period) among 308 4-to 9-year-old children living in floricultural communities in Ecuador in 2008 who participated in the ESPINA study. Children's neurobehavior was examined once (NEPSY-II: 11 subtests covering 5 domains), between 63 and 100days (SD: 10.8days) after Mother's Day harvest (blood acetylcholinesterase activity levels can take 82days to normalize after irreversible inhibition with organophosphates).ResultsThe mean (SD) neurobehavioral scaled scores across domains ranged from 6.6 (2.4) to 9.9 (3.3); higher values reflect greater performance. Children examined sooner after Mother's Day had lower neurobehavioral scores than children examined later, in the domains of (score difference per 10.8days, 95%CI): Attention/Inhibitory Control (0.38, 0.10-0.65), Visuospatial Processing (0.60, 0.25-0.95) and Sensorimotor (0.43, 0.10-0.77). Scores were higher with longer time post-harvest among girls (vs. boys) in Attention/Inhibitory Control.ConclusionsOur findings, although cross-sectional, are among the first in non-worker children to suggest that a peak pesticide use period may transiently affect neurobehavioral performance, as children examined sooner after the flower harvest had lower neurobehavioral performance than children examined later. Studies assessing pre- and post-exposure measures are needed.

Organophosphate pesticide (OP) poisoning is quite common and can cause cardiovascular complications and even direct myocardial injury. However, no guideline has included an acute poisoning as a potential cause for a type 2 myocardial infarction (MI) so far. Here we present a case of a 61-year-old woman brought by ambulance to emergency department one hour after accidental ingestion of an unknown quantity of a solution she used against flea infestation. The patient presented with dizziness, myosis, excessive sweating, hypersalivation, sphincteric incontinence, muscle fasciculation, tremor of the extremities, pale skin, alcoholic and pesticide breath odour. Even though we had no guidelines to fall back on, we successfully treated the patient with low-molecular-weight heparin, antiplatelets, statin, diltiazem, antidote therapy, and supportive care. Physicians should be aware that OP poisoning can induce type 2 MI as a complication within a few hours since exposure, and emergency management should always include close cardiac monitoring.

Industrial production of food for animals and humans needs increasing amounts of pesticides, especially of organophosphates, which are now easily available worldwide. More than 3 million cases of acute severe poisoning are estimated to occur worldwide every year, and even more cases remain unreported, while 200,000–350,000 incidentally or intentionally poisoned people die every year. Diagnostic and therapeutic procedures in organophosphate poisoning have, however, remained unchanged. In addition to several neurologic symptoms (miosis, fasciculations), hypersecretion of salivary, bronchial, and sweat glands, vomiting, diarrhea, and loss of urine rapidly induce dehydration, hypovolemia, loss of conscience and respiratory distress. Within hours, signs of acidosis due to systemic hypoxia can be observed at first laboratory investigation after hospitalization. While determination of serum-cholinesterase does not have any diagnostic value, it has been established that hypoalbuminemia alone or accompanied by an increase in creatinine, lactate, or C-reactive protein serum levels has negative prognostic value. Increased serum levels of C-reactive protein are a sign of systemic ischemia. Protective mechanical ventilation should be avoided, if possible. In fact, acute respiratory distress syndrome characterized by congestion and increased weight of the lung, accompanied by heart failure, may become the cause of death. As the excess of acetylcholine at the neuronal level can persist for weeks until enough newly, locally synthesized acetylcholinesterase becomes available (the value of oximes in reducing this time is still under debate), after atropine administration, intravenous albumin and fluid infusion should be the first therapeutic interventions to reestablish normal blood volume and normal tissue oxygenation, avoiding death by cardiac arrest.

Background and Objective: Organophosphates poisoning is among the most prevalent forms of intentional and unintentional poisoning in Pakistan. However, the actual burden of AKI secondary to organophosphate poisoning in Pakistani population is still not known. This study aimed to determine the actual burden of AKI among patients admitted at National Poison Control Centre, Karachi. Methods: A cross-sectional survey was conducted at National Poison Control Centre, Karachi November, 2013 to April, 2014. A sample of 300 patients of age 18 years and above, presenting with organophosphate poisoning within 24 of exposure or ingestion were included in the study. Frequency of acute kidney injury was calculated using the diagnostic criteria of serum creatinine level of >1.4 mg/dL. Data was analyzed using SPSS version 19. Results: The frequency of AKI which was defined as creatinine level >1.4 mg/dL was 22.3% (n=67). However, there was no statistically significant difference was found in frequency of AKI on the basis of age, sex, amount of organophosphates ingested and BMI. This study found statistically significant differences in the AKI frequency on the basis of lag time. Those who presented earlier after poisoning had relatively low frequency of AKI. Conclusion: This study concludes that AKI is a common complication among patients presenting with organophosphate poisoning at National Poison Control Center, Karachi. Lag time is a key determinant of AKI among patients with organophosphate poisoning. Timely treatment can prevent this critical complication among patients with organophosphate poisoning. [ABSTRACT FROM AUTHOR]

Objective: There is insufficient evidence on the effectiveness of gastric lavage in organophosphorus poisoning. This study was done to quantitate the level of chlorpyrifos and quinalphos retrieved in gastric lavage fluid. Methods: Patients presenting within six hours of ingesting quinalphos or chlorpyrifos with International Program on Chemical Safety Poison Severity Score (IPCS PSS) grade 2 or more were included in the study. After the stabilisation of patients, gastric lavage was performed with alliquotes of 200 ml of normal saline till aspirate became clear. Quantification of the pesticide was done in the first 10 ml of lavage fluid aspirated out and in blood with gas chromatography with triple quadruple mass spectrometer (GC-MSMS). Results: There were six patients in each pesticide group. Mean time for reaching hospital after the ingestion of pesticide was 2.8 ± 1.1(range 1.25-6) hours. Median quantity of chlorpyrifos in the lavage fluid was 10.24 (IQR 14.36) µg/L and in quinalphos, it was 1360.62 (IQR 1691.2) µg/L. Other compounds detected in lavage fluid and confirmed in blood were endosulfan, diazinon, pirimiphos, pyridafenthion, pyrazophos, pirimiphos ethyl, and azinphos. Conclusion: Chlorpyrifos and quinalphos are detected in lavage fluid after one hour of ingestion and few milligrams are retrieved by gastric lavage. The presence of other pesticides including endosulfan were confirmed in lavage fluid. [ABSTRACT FROM AUTHOR]

The high toxicity of organophosphorus compounds originates from covalent inhibition of acetylcholinesterase (AChE), an essential enzyme in cholinergic neurotransmission. Poisonings that lead to life-threatening toxic manifestations require immediate treatment that combines administration of anticholinergic drugs and an aldoxime as a reactivator of AChE. An alternative approach to reduce the in vivo toxicity of OPs focuses on the use of bioscavengers against the parent organophosphate. Our previous research showed that AChE mutagenesis can enable aldoximes to substantially accelerate the reactivation of OP-enzyme conjugates, while dramatically slowing down rates of OP-conjugate dealkylation (aging). Herein, we demonstrate an efficient HI-6-assisted VX detoxification, both ex vivo in human blood and in vivo in mice by hAChE mutants modified at the choline binding site (Y337A and Y337A/F338A). The catalytic scavenging of VX in mice improved therapeutic outcomes preventing lethality and resulted in a delayed onset of toxicity symptoms.

Acetylcholinesterase (AChE; EC 3.1.1.7), an essential enzyme of cholinergic neurotransmission in vertebrates, is a primary target in acute nerve agent and organophosphate (OP) pesticide intoxication. Catalytically inactive OP-AChE conjugates formed between the active-center serine and phosphorus of OPs can, in principle, be reactivated by nucleophilic oxime antidotes. Antidote efficacy is limited by the structural diversity of OP-AChE conjugates resulting from differences in the structure of the conjugated OP, the different active-center volumes they occupy when conjugated to the active-center serine of AChE, and the distinct chemical characteristics of both OPs and oximes documented in numerous X-ray structures of OP-conjugated AChEs. Efforts to improve oxime reactivation efficacy by AChE structure-based enhancement of oxime structure have yielded only limited success. We outline here the potential limitations of available AChE X-ray structures that preclude an accurate prediction of oxime structures, which are necessary for association in the OP-AChE gorge and nucleophilic attack of the OP-conjugated phosphorus.

Exposures to seizure-inducing chemical threat agents are a major public health concern. Of particular need is improved treatment to terminate convulsions and to prevent the long-term neurological sequelae in survivors. We are studying the organophosphorus cholinesterase inhibitor diisopropyl fluorophosphate (DFP) and the GABA receptor inhibitor tetramethylenedisulfotetramine (TETS), which arguably encompass the mechanistic spectrum of seizure-inducing chemical threats, with the goal of identifying therapeutic approaches with broad-spectrum efficacy. Research efforts have focused on developing translational models and translational diagnostic approaches, including (1) in vivo models of DFP- and TETS-induced seizures for studying neuropathological mechanisms and identifying treatment approaches; (2) in vivo imaging modalities for noninvasive longitudinal monitoring of neurological damage and response to therapeutic candidates; and (3) higher-throughput in vitro platforms for rapid screening of compounds to identify potential antiseizure and neuroprotective agents, as well as mechanistically relevant novel drug targets. This review summarizes our progress toward realizing these goals and discusses best practices and mechanistic insights derived from our modeling efforts.

On March 4, 2018, two casualties collapsed on a park bench in Salisbury, Wiltshire, UK. They were later discovered to have been the victims of an attempted murder using the Soviet-era Novichok class of nerve agent. The casualties, along with three further critically ill patients, were cared for in Salisbury District Hospital's Intensive Care Unit. Before the COVID-19 pandemic, the Salisbury and Amesbury incidents were the longest-running major incidents in the history of the UK National Health Service. This narrative review seeks to reflect on the lessons learned from these chemical incidents, with a particular focus on hospital and local organisational responses. [ABSTRACT FROM AUTHOR]

Abebe Getie, Yaschilal Muche Belayneh Department of Pharmacy, College of Medicine and Health Sciences, Wollo University, Dessie, EthiopiaCorrespondence: Yaschilal Muche BelaynehDepartment of Pharmacy, College of Medicine and Health Sciences, Wollo University, P.O. Box 1145, Dessie, EthiopiaTel +251918092466Email yaschilal.muche19@gmail.comBackground: Poisoning causes significant patient morbidity and mortality worldwide. It is a common reason for emergency department visits and hospitalizations. Acute poisoning needs immediate effective management to prevent patient mortality or sequela. This study was carried out to determine the pattern of acute poisoning cases and their management at the emergency department of Dessie referral hospital, northeast Ethiopia.Methods: A retrospective cross-sectional study of all registered poisoning cases managed at the emergency department of Dessie referral hospital was conducted from March 10 to May 2, 2018.Results: There were a total of 147 registered poisoning cases listed in the registry during the study period, of which 120 cases (81.6%) had complete data and were included in the study. Among the total of 120 studied poisoning cases, 66 (55%) were females, and 53 (44.2%) were in the age group of 21– 30 years. The causative poison was documented for 118 cases. Organophosphates were the most common poisoning agents involved in 54 (45%) of the cases followed by sodium hypochlorite, 27 (22.5%), and food poisoning, 19 (15.8%). Among the total patients, 77 (64.2%) were self-poisoned intentionally, 31 (25.8%) were poisoned in an unintentional manner and the rest, 12 (10%), had an unknown manner of poisoning. Mental disorder, 25 (20.8%); family disharmony, 23 (19.2%); and marital disharmony, 19 (15.8%) were the three most common causes of intentional poisoning. In all cases of acute poisoning, both pharmacological and non-pharmacological treatment approaches were used. Cimetidine was the most commonly used pharmacologic treatment, 118 (98.3%), followed by antiemetic, 107 (89.2%); proton pump inhibitor, 87 (72.5%), and atropine, 67 (55.8%). ANOVA did not show a statistically significant difference (P> 0.05) in the frequency of poisoning cases across seasons.Conclusion: Among 120 acute poisoning cases, 77 (64.2%) were intentional poisoning cases. Organophosphate poisoning accounts for 45% of the total poisoning cases. The three major reasons for intentional poisoning were mental disorders (20.8%), family disharmony (19.2%) and marital disharmony (15.8%). Cimetidine (98.3%) was the most commonly used pharmacologic treatment of the poisoning cases.Keywords: acute poisoning, emergency department, organophosphate poisoning

Organophosphate (OP) poisoning is a critical public health issue, particularly in agricultural regions where these compounds are extensively used as pesticides. The toxic effects of OP compounds arise from their inhibition of acetylcholinesterase, leading to an accumulation of acetylcholine and a subsequent cholinergic crisis, which can be fatal if not promptly treated. Traditional management of OP poisoning includes the administration of atropine and pralidoxime; however, these treatments often fall short of reducing the high morbidity and mortality associated with severe cases. Recent research has highlighted the potential of magnesium sulfate as an adjunctive treatment for OP poisoning. Magnesium sulfate exerts its beneficial effects through mechanisms such as calcium channel blockade and stabilization of neuromuscular junctions, which help mitigate the cholinergic hyperactivity induced by OP compounds. Clinical studies have shown that magnesium sulfate can significantly reduce the duration of intensive care unit (ICU) stays and improve overall patient outcomes. This narrative review aims to comprehensively analyze current insights into using magnesium sulfate to manage OP poisoning. It discusses the pathophysiology of OP poisoning, the pharmacological action of magnesium sulfate, and the clinical evidence supporting its use. Furthermore, the review will address the safety profile of magnesium sulfate and its potential role in current treatment guidelines. By synthesizing available evidence, this review seeks to establish magnesium sulfate as a game-changer in the management of OP poisoning, ultimately contributing to better clinical practices and patient outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nelakuditi et al.)

Organophosphate poisoning (OPP) remains a significant public health issue globally, particularly in middle- and low-income countries. This study aimed to assess the effectiveness of physiotherapy interventions in managing patients with OPP, focusing on reducing the severity of intermediate syndrome symptoms and associated complications such as respiratory muscle weakness and bilateral loculated pleural effusions. A 48-year-old male with a history of alcohol consumption was transferred to the medicine intensive care unit due to poison ingestion. The patient exhibited symptoms of respiratory distress and decreased consciousness, necessitating intubation and mechanical ventilation. Physiotherapy interventions included patient education, secretion mobilization, vital capacity improvement, secondary complication prevention, chest expansion exercises, dyspnea-relieving positions, and mobilization. The patient's progress was monitored using various scales, including the Functional Independence Measure Scale, ICU Mobility Scale, and Chelsea Critical Care Physical Assessment Tool. Significant improvements in functional independence, mobility, and psychological well-being were observed throughout the intervention period. This study highlights the importance of physiotherapy in the comprehensive management of OPP, emphasizing its role in mitigating respiratory complications and improving overall functional outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vikhe et al.)

While accidental poisoning is fairly common in children, the data are sparse when organophosphate (OP) is considered the culprit toxin. Only case reports of such patients from the Southeast Asian Region have been documented, despite it contributing largely to the global burden of organophosphorus poisoning in the adult population. This can be attributed to difficulty in diagnosing children because of varied presentations in the pediatric population and unreliable or unavailable exposure history. We present a case of a 19-month-old toddler who presented to the ED with OP poisoning, which proved to be a diagnostic and management challenge because of more common differentials and the unavailability of a clear history., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patel et al.)

Fenitrothion is one of the most globally used organophosphorus pesticides, which can cause neurological symptoms, including involuntary movements. However, due to the limited number of case report, information on its treatment is also scarce. Here we presented a 74-year-old Japanese woman who was admitted to our hospital due to a persistent nausea and vomiting after ingesting 200 mL of 50% fenitrothion for a suicidal attempt. She received continuous intravenous infusion of atropine and 2-pyridine aldoxime methiodide under mechanical ventilation and continuous hemodiafiltration. However, she developed fasciculations of the face and right arm on day 11, which raised suspicions of delayed neuropathy associated with organophosphorus poisoning. To reduce the risk of respiratory depression, she received intravenous levetiracetam at a dosage of 1,000 mg/day. However, as her fasciculations persisted, the levetiracetam dosage was adjusted to 2,000 mg/day on day 14. On the following day, her fasciculations subsided. Neurologic symptoms of lipid-soluble organophosphorus poisoning, including fenitrothion, can sometimes delay following ingestion. Temporary administration of levetiracetam may prove effective in alleviating fasciculations.

Background: Organophosphate poisoning is a serious issue and it results in significant casualties in developing countries. Since agriculture remains an important and necessary sector of human society and organophosphate are commonly used in agriculture, it is difficult to prevent organophosphate poisoning. Gastrointestinal bleeding is not a common but life threatening symptom of organophosphate poisoning. We report a rare case of gastrointestine bleeding due to organophosphate poisoning.Case Presentation: A 78-year-old woman presented to our hospital approximately 12 h after ingesting a mouthful of organophosphate and benzodiazepines in a suicide attempt. Six weeks after successful medical treatment for respiratory failure, she developed recurring melena. Colonoscopy and esophagogastroduodenoscopy findings were negative for ulcers or bleeding. Enteroscopy revealed severe circumferential ulcers with luminal narrowing 10 cm proximal to the ileocecal valve. The patient underwent a 100-cm ileum resection after failed medical treatment and recovered uneventfully. The resected terminal ileum demonstrated severe inflammation and a sharp transitional zone between the healthy and injured mucosa approximately 50 cm proximal to the ileocecal valve. Pathological examination revealed an injured mucosa with inflammatory cell infiltration and structural damage. This case highlights a rare event of OP poisoning with late-onset lower gastrointestinal bleeding, which prolonged the patient's recovery course and parenteral alimentation period.Conclusion: We report a rare case of a patient with organophosphate poisoning, with late-onset lower GI tract bleeding, which raised clinical awareness regarding the organophosphate poisoning that induce intestinal symptoms. [ABSTRACT FROM AUTHOR]

We conducted a randomized-controlled trial of a home-based intervention to reduce pesticide exposures to farmworkers' children in Monterey County, California (n=116 families). The intervention consisted of three home-based educational sessions delivered by community health workers in Spanish. Measurements of organophosphate (OP) insecticide metabolites in child urine (n=106) and pesticides in home floor wipes (n=103) were collected before and after the intervention. Median child urinary dialkyl phosphate (DAP) metabolite levels were slightly lower among the intervention group children at follow-up compared with baseline, albeit nonsignificantly. DAP metabolite levels in the control group children were markedly higher at follow-up compared with baseline. In adjusted models, intervention participation was associated with a 51% decrease in total DAP metabolite levels. Carbaryl, chlorpyrifos, cypermethrin, dacthal, diazinon, malathion, and trans-permethrin were commonly detected in the floor wipes. In adjusted models, intervention participation was significantly associated with a 37% decrease in trans-permethrin floor wipe levels in homes, but not OP or other agricultural pesticides. In summary, intervention group children had slightly reduced pesticide exposures, whereas child exposures were higher among the control group. Additional intervention studies evaluating methods to reduce pesticide exposures to farmworker families and children are needed.

For the first time, the efficacy of post-exposure treatment of organophosphate (OP) poisoning was increased by transdermal delivery of acetylcholinesterase (AChE) reactivator pyridine-2-aldoxime methochloride (2-PAM) as a preventive countermeasure. By selecting the optimal ratio of components, classical transfersomes (based on soybean phosphatidylcholine and Tween 20) and modified transfersomes (based on soybean phosphatidylcholine, Tween 20 and pyrrolidinium cationic surfactants with different hydrocarbon tail lengths) were obtained for 2-PAM encapsulation. Transfersomes modified with tetradecylpyrrolidinium bromide showed the best results in encapsulation efficiency and sustained release of 2-PAM from vesicles. Using Franz cells, it was found that the incorporation of surfactants into PC liposomes results in a more prolonged release of 2-PAM through the rat skin. Transfersomes containing 2-PAM, after exhaustive physical and chemical characterization, were embedded in a gel based on Carbopol® 940. A significantly high degree of erythrocyte AChE reactivation (23 ± 7%) was shown for 2-PAM in unmodified transfersomes in vivo. Preliminary transdermal administration of 2-PAM 24 h before emergency post-exposure treatment of OP poisoning leads to an increase in the survival rate of rats from 55% to 90%.

Background: Human serum paraoxonase 1 (PON1) hydrolyzes organophosphate (OP) compounds and so significantly alters an individual’s susceptibility to the toxicity of these chemicals. The study was designed to assess the serum PON1 activity in a series of patients with OP poisoning. Methods: Suspected OP poisoning patients presented within 6 hours of consumption at emergency department were recruited. Demographic information of patients, clinical findings, treatments given, complications, length of hospital stay and clinical outcome were collected into datasheets. Patients were graded into moderate and severe poisoning. Serum PON1 was measured by ELISA method and serum cholinesterase by butyrylthiocholine method. Results: Mean serum PON1 level in patients with severe poisoning was significantly lower than those with moderate poisoning (426 ± 179 U/L vs. 868 ± 79 U/L, P < 0.001). Serum PON1 significantly correlated with serum cholinesterase levels (r = 0.400, P < 0.001) and negatively associated with total length of hospital stay (r = -0.338, P < 0.001), total atropine dose (r = -0.826, P < 0.001), serum amylase (r = -0.331, P < 0.001), lipase (r = 0.260, P = 0.011) and total creatinine kinase (r = -0.456, P < 0.001). Serum PON1 and cholinesterase levels were significantly lower in expired patients and those who required ventilation assistance as compared to recovered patients who did not require ventilation assistance. Conclusion: Lower PON1 activity was significantly associated with lower serum cholinesterase and poorer outcomes. PON1 activity may be considered as an indicator of prognosis in OP poisoning.

Objective: Organophosphates (OPs) are widely used for pest control worldwide, leading to increased risk for human exposure. The acute hormonal effects of OP include deficiencies in the thyroid-stimulating hormone (TSH), adrenocorticotropic hormone, and insulin-like growth factor 1 hormone correlated with the levels of cholinesterase. Most patients with OP-related hormone deficiency recover at 3 months of follow-up. However, the chronic effects of these chemicals are not clear. The aim of the present study was to determine the chronic influences of OP on pituitary functions in patients who had OP poisoning. Materials and Methods: This prospective study was performed in Erciyes University Medical School. All of the patients who had OP poisoning were followed up in the medical intensive care unit (MICU). They were evaluated after discharge from the MICU after at least 6 months with regard to pituitary functions. In all patients, data were extracted from the MICU records. Baseline hormone levels were assessed, and dynamic tests (insulin tolerance test and glucagon stress test) were performed. Results: Twenty-nine adult patients (13 women and 16 men) with OP poisoning were included in the study. The mean age of the patients was 41.9+-16.7 years. The mean time from hospitalization to assessment of pituitary functions was 43.9+-15.8 months in patients with OP poisoning. All patients had normal prolactin, TSH, follicle-stimulating hormone, and luteinizing hormone levels. Women had normal estrogen levels, and men had normal total testosterone levels. Cortisol deficiency was detected in only 1 (3.4%) patient, and growth hormone (GH) insufficiency was found in 3 (10.3%) patients. Conclusion: GH and cortisol axis may be affected by OP poisoning in the long term. Thus, pituitary hormone levels should be tested following an acute period in patients with OP.

Background: Organophosphates (OPs) are regularly utilized as pesticides all over the world. Exposures to OPs cause countless cases of poisoning and death annually. Organophosphates inebriation generates a range of muscarinic, nicotinic, and cholinergic side effects including both central and peripheral nervous systems. OP compound’s simple accessibility is responsible for expanding rates of pesticide poisoning and the fact that it is a noteworthy reason for morbidity and mortality that presents general medical issues in a growing district. Methods: I performed a review of the published literature. The databases Medline, Embase, Scopus and Google Scholar were searched using the terms intermediate syndrome, organophosphate induces intermediate syndrome and organophosphate poisoning. Databases were merged and a duplicate was removed. Results: In intense organophosphate poisoning, serious and delayed acetylcholinesterase restraint comes with oxidative stress, identified in erythrocyte membranes, that takes place in the initial phases of poisoning and may add to the progress and seriousness of intermediate syndrome (IMS). Conclusion: It normally appears 2-4 days after presentation when the side effects and indications of the intense cholinergic disorder (e.g., muscle fasciculations, muscarinic signs) are not evident anymore. However, IMS has been considered as a noteworthy causative factor of organophosphate-related morbidity and mortality due to its incessant presence and potential occurrence of breathing malfunction. The aim of the article is to bring down the clear idea about the IMS.

Introduction: Acute organophosphate (OP) poisoning is one of the most common poisoning causing significant morbidity and mortality in developing countries. Acute cholinergic manifestations predominate with many patients requiring intensive care management and ventilator support. Nerve conduction studies including repetitive nerve stimulation can evaluate the altered neuromuscular transmission and peripheral nerve function by OPs. Objective: To evaluate the electrophysiological abnormalities in patients with acute OP poisoning and correlate with clinical status. Materials and Methods: Patients with acute OP poisoning admitted from August 2016 to August 2017 were prospectively studied. Nerve conduction studies including phrenic nerve conduction were performed within 24 h of admission. Repetitive nerve stimulation was performed at 3 and 30 Hz. Nerve conduction findings were compared with data from age-matched healthy controls. Results: Thirty patients were included (18 men and 12 women) in the study. Their age ranged from 16 to 47 years (30 ± 9.2). The first assessment revealed a mild reduction of compound muscle action potential (CMAP) amplitude and reduced F-wave persistence. Eleven patients had repetitive CMAPs suggesting cholinergic excess. Seven among the 11 patients requiring mechanical ventilation had decrement–increment response with 30 Hz stimulation and reduced diaphragmatic CMAP amplitude (P = 0.02). Conclusion: The presence of repetitive CMAPs, decrement–increment response to tetanic stimulation and reduced diaphragmatic CMAP amplitude in OP poisoning patients correlate with neuromuscular paralysis and need for mechanical ventilation.

Organophosphate (OP) compounds include highly toxic chemicals widely used both as pesticides and as warfare nerve agents. Existing countermeasures are lifesaving, but do not alleviate all long-term neurological sequelae, making OP poisoning a public health concern worldwide and the search for fully efficient antidotes an urgent need. OPs cause irreversible acetylcholinesterase (AChE) inhibition, inducing the so-called cholinergic syndrome characterized by peripheral manifestations and seizures associated with permanent psychomotor deficits. Besides immediate neurotoxicity, recent data have also identified neuroinflammation and microglia activation as two processes that likely play an important, albeit poorly understood, role in the physiopathology of OP intoxication and its long-term consequences. To gain insight into the response of microglia to OP poisoning, we used a previously described model of diisopropylfluorophosphate (DFP) intoxication of zebrafish larvae. This model reproduces almost all the defects seen in poisoned humans and preclinical models, including AChE inhibition, neuronal epileptiform hyperexcitation, and increased neuronal death. Here, we investigated in vivo the consequences of acute DFP exposure on microglia morphology and behaviour, and on the expression of a set of pro- and anti-inflammatory cytokines. We also used a genetic method of microglial ablation to evaluate the role in the OP-induced neuropathology. We first showed that DFP intoxication rapidly induced deep microglial phenotypic remodelling resembling that seen in M1-type activated macrophages and characterized by an amoeboid morphology, reduced branching, and increased mobility. DFP intoxication also caused massive expression of genes encoding pro-inflammatory cytokines Il1β, Tnfα, Il8, and to a lesser extent, immuno-modulatory cytokine Il4, suggesting complex microglial reprogramming that included neuroinflammatory activities. Finally, microglia-depleted larvae were instrumental in showing that microglia were major actors in DFP-induced neuroinflammation and, more importantly, that OP-induced neuronal hyperactivation was markedly reduced in larvae fully devoid of microglia. DFP poisoning rapidly triggered massive microglia-mediated neuroinflammation, probably as a result of DFP-induced neuronal hyperexcitation, which in turn further exacerbated neuronal activation. Microglia are thus a relevant therapeutic target, and identifying substances reducing microglial activation could add efficacy to existing OP antidote cocktails.

Introduction The development of an extrapyramidal syndrome (EPS) is assumed to be a potential and important consequence of organophosphate poisoning (OP). Even though its causal relationship is firmly established, the information available in the literature regarding the orientation to be given is scarce, and its approach remains shrouded in a significant degree of uncertainty. Catatonia, as a neuropsychiatric condition, may present a marked overlap with the set of extrapyramidal symptoms developed after OP. Does the overlap between the symptoms seen in catatonia and in EPS make differential diagnosis fundamental or does it have no relevance in relation to the approach to be established? Objectives To discuss the therapeutic approach to be implemented in the extrapyramidal symptoms resulting from OP and reflect on the overlap between catatonia and EPS. Methods Presentation of a clinical case and review of the literature. Results A 50-year-old woman with major depressive disorder developed a condition marked by exuberant extrapyramidal symptoms 3 weeks after OP. Significant stiffness, tremor, dysphagia and facial hypomimia were some of the symptoms observed. Therapy was started with amantadine 100mg daily, with complete resolution of the symptoms after 5 days. Follow-up revealed reversal of extrapyramidal symptoms, in the absence of any neuroimaging changes or any other neuropsychiatric manifestations. Conclusions The possible overlap between catatonia and EPS is remarkable. The two conditions, regardless of their differentiation, may benefit from an identical approach using dopaminergic drugs. The use of amantadine, even in low doses, may be an option in the rapid reversal of extrapyramidal symptoms resulting from OP. Disclosure No significant relationships.

Organophosphate pesticide (OP) poisoning is quite common and can cause cardiovascular complications and even direct myocardial injury. However, no guideline has included an acute poisoning as a potential cause for a type 2 myocardial infarction (MI) so far. Here we present a case of a 61-year-old woman brought by ambulance to emergency department one hour after accidental ingestion of an unknown quantity of a solution she used against flea infestation. The patient presented with dizziness, myosis, excessive sweating, hypersalivation, sphincteric incontinence, muscle fasciculation, tremor of the extremities, pale skin, alcoholic and pesticide breath odour. Even though we had no guidelines to fall back on, we successfully treated the patient with low-molecular-weight heparin, antiplatelets, statin, diltiazem, antidote therapy, and supportive care. Physicians should be aware that OP poisoning can induce type 2 MI as a complication within a few hours since exposure, and emergency management should always include close cardiac monitoring. [ABSTRACT FROM AUTHOR]

Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals' resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD 50 of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood-brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development.

Introduction: Background: Childhood poisoning, characterised by exposure to toxic substances, poses a global health concern with variations across regions. Despite the importance of having current information about childhood acute poisoning in our region, there is a noticeable gap in such research in our local context. Regularly reviewing the agents responsible for poisoning in our locale is essential for devising prevention strategies and treatment approaches. This study aimed to examine the patterns and outcomes of childhood poisoning at the Children's Emergency Department of the Federal Medical Centre, Yenagoa, Bayelsa State, Nigeria., Methods: A retrospective cross-sectional study was conducted, analysing cases of childhood poisoning in the Children's Emergency Ward, presenting from January 2013 to December 2022. Sociodemographic data, types of poisoning agents, home interventions, clinical features and outcomes were extracted from medical records., Results: Of 9389 admissions, 81 (0.8%) cases were admitted for childhood poisoning, but only 69 cases were analysed (total n=69). Children aged under 5 years (52.2%) and who were males (59.4%) were mostly involved. Organophosphates (21.7%) and kerosene (20.3%) were common poisoning agents, often accidental (72.5%) and occurring at home (94.2%). Delayed hospital presentation (>2 hours) was common (68.1%). Vomiting (72.5%) and drooling saliva (56.5%) were prevalent symptoms. Hydration (60.9%) was the main hospital intervention, while antidotes were infrequently used (15.9%). Mortality was 8.7%, predominantly due to kerosene ingestion in young children., Conclusion: Organophosphate and kerosene poisoning are the most common in this facility. Enforcement challenges persist, emphasising the importance of safe storage practices and improved poison control measures. Addressing resource constraints for antidote availability and increasing awareness are vital for effective management and prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Organophosphorus (OP) nerve agents inhibit acetylcholinesterase (AChE), creating a cholinergic crisis in which death can occur. The phosphylated serine residue spontaneously dealkylates to the OP-aged form, which current therapeutics cannot reverse. Soman's aging half-life is 4.2 min, so immediate recovery (resurrection) of OP-aged AChE is needed. In 2018, we showed pyridin-3-ol-based quinone methide precursors (QMPs) can resurrect OP-aged electric eel AChE in vitro , achieving 2% resurrection after 24 h of incubation (pH 7, 4 mM). We prepared 50 unique 6-alkoxypyridin-3-ol QMPs with 10 alkoxy groups and five amine leaving groups to improve AChE resurrection. These compounds are predicted in silico to cross the blood-brain barrier and treat AChE in the central nervous system. This library resurrected 7.9% activity of OP-aged recombinant human AChE after 24 h at 250 μM, a 4-fold increase from our 2018 report. The best QMP ( 1b ), with a 6-methoxypyridin-3-ol core and a diethylamine leaving group, recovered 20.8% (1 mM), 34% (4 mM), and 42.5% (predicted maximum) of methylphosphonate-aged AChE activity over 24 h. Seven QMPs recovered activity from AChE aged with Soman and a VX degradation product (EA-2192). We hypothesize that QMPs form the quinone methide (QM) to realkylate the phosphylated serine residue as the first step of resurrection. We calculated thermodynamic energetics for QM formation, but there was no trend with the experimental biochemical data. Molecular docking studies revealed that QMP binding to OP-aged AChE is not the determining factor for the observed biochemical trends; thus, QM formation may be enzyme-mediated.

Organophosphorus agents are easily absorbed via respiratory, gastrointestinal, and dermal routes, and inhibit the acetylcholine transferase enzyme (AChE), which is responsible for the majority of toxicity caused by organophosphates in the body. A comprehensive search was conducted across three prominent databases, namely Google Scholar, PubMed, and Science Direct, to identify relevant articles published. The search focused on the keywords "MgSO4" or "magnesium sulfate" in conjunction with "organophosphate" or "organophosphate poisoning." Inhibition of AChE results in the accumulation of acetylcholine (ACh) in synapses and stimulation of cholinergic receptors. Considering that several studies have shown the use of magnesium sulfate (MgSO4) in inhibiting the release of ACh in the central and peripheral sympathetic and parasympathetic synapses, this study was conducted to review the role of MgSO4 in the treatment of OP. The intravenous administration of MgSO4 exhibits favorable tolerability and clinical efficacy in alleviating cardiac toxicity associated with OP exposure.

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n=120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P≤0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P≤0.05) and PON1 192 (P≤0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal.

Translational research is needed to understand and predict the neurotoxic consequences associated with repeated occupational exposures to organophosphorus pesticides (OPs). In this report, we describe a research strategy for identifying biomarkers of OP neurotoxicity, and we characterize pesticide application workers in Egypt's Menoufia Governorate who serve as our anchor human population for developing a parallel animal model with similar exposures and behavioral deficits and for examining the influence of human polymorphisms in cytochrome P450 (CYP) and paraoxonase 1 (PON1) enzymes on OP metabolism and toxicity. This population has previously been shown to have high occupational exposures and to exhibit a broad range of neurobehavioral deficits. In addition to observational studies of work practices in the field, questionnaires on demographics, lifestyle and work practices were administered to 146 Egyptian pesticide application workers applying pesticides to the cotton crop. Survey results indicated that the application workforce uses standard operating procedures and standardized equipment provided by Egypt's Ministry of Agriculture, which provides a workforce with a stable work history. We also found that few workers report using personal protective equipment (PPE), which likely contributes to the relatively high exposures reported in these application workers. In summary, this population provides a unique opportunity for identifying biomarkers of OP-induced neurotoxicity associated with occupational exposure.

Background: Acute organophosphate poisoning (AOPP) is related to several clinical complications that may be fatal. The aim of this study was to evaluate the effects of demographic, clinical and laboratory findings on AOPP outcome. Methods: In this retrospective cross-sectional study, medical records of all patients with AOPP admitted to Imam Reza Hospital, Mashhad, Iran, were reviewed from January 2016 to December 2017. Demographic data, clinical presentations, erythrocyte cholinesterase (RBC-ChE) and serum cholinesterase (S-ChE) activities were studied and evaluated in relation to clinical outcome of the patients. Results: A total of 64 patients (37 male, 27 female) were evaluated from whom 6 patients (9.4%) died. Statistically significant relationships were found between the outcome of the patients and RBC-ChE activity (p =0.008), intratracheal intubation (p=0.003), and abnormal blood pressure (p =0.009). Despite the lower mean S-ChE levels in the deceased patients and loss of consciousness in 42.2% (n=27) of patients, there was no statistically significant correlations between these factors and patients’ outcome (p =0.147, p =0.075, respectively). Conclusion: RBC-ChE activity, need for intratracheal intubation, and abnormal blood pressure on admission were important predictive factors in the clinical outcome of AOPP. Although S-ChE activity, level of consciousness, white blood cell count and blood glucose level on admission provide useful information, these data had no prognostic value in patients with AOPP.

Background: Organophosphate (OP) poisoning is a global issue, causing over 200,000 deaths annually especially in developing countries, such as Sri Lanka and India. Clinical presentation of a typical OP poisoning may follow three well-defined phases. The initial phase is an acute cholinergic crisis, after that Intermediate Syndrome (IMS) may develop within 24-96 hours, and lastly, Organophosphate-Induced Delayed Polyneuropathy (OPIDPN) may present after 2-3 weeks. The signs and symptoms of the IMS are weakness of the respiratory muscles, including the diaphragm, intercostal, accessory, neck, and proximal limbs muscles. The aim of this study was to highlight the clinical profile of the IMS following organophosphate poisoning. Methods: This descriptive, prospective, and cross-sectional study was conducted at the Teaching Hospital, Batticaloa, Sri Lanka, over a period of 6 months from March 1, 2017 to August 31, 2017. Results: Of the total 65 enrolled patients, 60% (n=39) were male. All patients ingested OP pesticide for deliberate self-harm and all of them had some degrees of initial cholinergic crises. The prevalence of IMS in the studied patients was 5.88%. All 5 patients with IMS had neck, facial and proximal limbs muscle weakness from whom, two cases (40%) had extra-ocular muscle paralysis. There was no in-hospital fatality among IMS patients. Conclusion: IMS is a rare and life-threatening problem in OP intoxication. Early diagnosis and intensive care management can prevent further complications and mortality. Prevalence of IMS in this study was lower than previous reports with almost similar clinical features.

Organophosphate (OP) poisoning is prevalent in developing countries. Toxicity occurs by voluntary injection, inhalation, and absorption. Self-injection is rare. The current case report describes a 61-y/o male with subcutaneous self-injected one cc OP poisoning presenting with delayed drowsiness, nausea, and vomiting. He was treated and presented a good clinical response to treatment with pralidoxime and had a successful recovery. Diagnosis of OP compound toxicity by the parenteral route is a challenge. By observing patients, the dose, and the time between poisoning until the time to start treatment, we can conclude different presentations and outcomes of OP poisoning.

Objectives: This study is designed to assess the mortality in OPP patients with low GCS scores. Study Design: Cross Sectional study. Setting: Jinnah Postgraduate Medical Center. Period: From 1st February 2018 to 31st August 2018. Material & Methods: Included patients with low GCS, both genders and age of 18-60 years diagnosed with OPP. Their GCS was calculated and the outcome was determined in terms of mortality. Results: Out of 70 patients, the mean age was 35.2+16.5 years with the majority (62.9%) <30 years. 62.9% of these were males. Most (57.1%) of them presented after ingestion of <15mL of OP, 60% had the poisoning for >60 minutes, and the majority (74.3%) had taken it orally. When the GCS was computed, 81.40% had that of >5, while the mean came out to be 6.64 ±1.43. The mortality rate here was 17.10%. Conclusion: GCS toll can be a helpful and practical tool in assessing the mortality among the patients of OPP. However, because of the limited literature on the subject further studies are recommended to improve its validity. [ABSTRACT FROM AUTHOR]

To evaluating the efficacy of fresh frozen plasma (FFP) in comparison with conventional regimen in the treatment of organophosphate (OP) poisoning. PubMed, ScopeMed, Cochrane, Scopus, and Google Scholar databases were searched. The search strategy used the following key words "organophosphate" and "poisoning or toxicity", "(atropine and oxime)", "fresh frozen plasma", "clinical trial", "outcome". The treatment with atropine or/and oxime was considered conventional therapy. The length of hospitalization, the length of ICU admission, need for mechanical ventilation and its duration, clinical recovery point, choline esterase level, mortality rate, and intermediate syndrome (IMS) occurrence were the key outcomes of interest. Databases were searched during the period of 2003–2019. Five studies were included in the analysis. Pooling of data showed that the relative risk (RR) of mortality in OP poisoning for five included trials comparing FFP-treated group with conventional regimen therapy was [0.563 (95% CI (0.252, 1.255)]. The summary of RR for IMS in two studies was [RR: 1.34, 95% CI (0.655, 2.742)]. In addition, there was a non-significant mean difference (MD) in hospital stay [MD: −0.106, 95% CI (−0.434, 0.223)] in three included trials. A significant MD was observed in the length of ICU admission in two trials between FFP-treated group compared to the conventional treatment group [MD: −2.672, 95% CI (−4.189, −1.154)], but after random effects meta-analysis, the changes were not significant [MD: −2.015, 95% CI (−6.308, 2.277)]. The summary of fixed-effect meta-analysis for choline esterase level in three trails was [MD: −0.117, 95% CI (−0.468, 0.234)]. The RR of ventilation requirement for two included trials in the FFP-treated group comparing to the conventional regimen therapy was [0.84, 95% CI (0.691, 1.022)] while for ventilation duration in two studies was [MD: −0.183, 95% CI (−0.567, 0.201)]. The addition of FFP to conventional therapy did not improve the outcomes of mortality, IMS, hospital length of stay, cholinesterase levels, need or duration of mechanical ventilation, and only the length of ICU stay could affect in the treated group. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of conjugates of adenine and uracil derivatives with triazole-hydroxamic acids moieties as uncharged reactivators of organophosphate-inhibited cholinesterases. • Development of acetylcholinesterase reactivators with improved blood–brain barrier permeability. • Interest as a treatment for delayed organophosphate neurotoxicity. A series of new uncharged conjugates of adenine, 3,6-dimetyl-, 1,6-dimethyl- and 6-methyluracil with 1,2,4-triazole-3-hydroxamic and 1,2,3-triazole-4-hydroxamic acid moieties were synthesized and studied as reactivators of organophosphate-inhibited cholinesterase. It is shown that triazole-hydroxamic acids can reactivate acetylcholinesterase (AChE) inhibited by paraoxon (POX) in vitro , offering reactivation constants comparable to those of pralidoxime (2-PAM). However, in contrast to 2-PAM, triazole-hydroxamic acids demonstrated the ability to reactivate AChE in the brain of rats poisoned with POX. At a dose of 200 mg/kg (i.v.), the lead compound 3e reactivated 22.6 ± 7.3% of brain AChE in rats poisoned with POX. In a rat model of POX-induced delayed neurodegeneration, compound 3e reduced the neuronal injury labeled with FJB upon double administration 1 and 3 h after poisoning. Compound 3e was also shown to prevent memory impairment of POX-poisoned rats as tested in a Morris water maze. [ABSTRACT FROM AUTHOR]

Although methidathion is an organophosphate insecticide, it is different from the other organophosphates in terms of toxicity. Because of its relatively high fat solubility, the apparent volume of methidathion distribution throughout the body is very high, indicating that hemoperfusion is not effective in removing this organophosphate from the body. Redistribution of methidathion from fat to blood can also occur when plasma levels diminish. Additionally, acetylcholinesterase aging, which is the loss of an alkyl side chain that prevents reactivation by oximes, is very rapid so that the effective reactivation by oximes is thwarted. Thus, methidathion’s effect on acetylcholinesterase inhibition is long lasting, particularly with a high dose. In addition to its parasympatholytic effect and ability to induce muscle paralysis, methidathion poisoning is associated with a profound and long-lasting circulatory collapse due to sympathetic ganglion blockade. This report presents the case of a 55-year-old man who accidentally ingested a high dose of methidathion. He later developed enteroinvasive aspergillosis infection-induced multiple bowel perforations on two separate occasions while on mechanical ventilator support, resulting in a fatal outcome. The renin-angiotensin axis activated by sympathetic ganglion blockade may have reduced the patient’s splanchnic blood flow, contributing to translocation of endotoxin. Also, the effect of excessive acetylcholine on non-neuronal acetylcholine receptors may have contributed to the development of fatal enteroinvasive aspergillosis in this patient.

Background: Exposure to environmental toxins such as organophosphates poses a great threat to the health of the public. In this work, we investigated the effects of continuous exposure to dichlorvos (DDVP) on kidney function and hematological parameters, and the possible antidote activity of Nigella sativa oil (NSO). Methods: This research was conducted in 2016, at The Animal Holding and Research Laboratory of Faculty Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Twenty-four Wistar rats were randomly divided into four groups, six rats each. The four groups received: 1. phosphate buffer solution as controls, 2. DDVP, 3. DDVP+NSO and 4. NSO alone. After 2 wk of treatment, blood samples were collected and hematological profile (RBC, Hb), erythrocyte indices (MCV, MCH, MCHC, and Plt), renal function parameters (albumin, urea, total protein, chloride, sodium, and potassium ions) and nonspecific immune response (WBC) were measured. Results: Rat exposed to DDVP showed red blood cell count, hemoglobin, packed cell volume, albumin, and total protein levels was reduced from control, while white blood cell count and urea significantly increased as compared to controls, the change in K+ level was not significant. NSO maintained optimal levels of red blood cell count, hemoglobin, packed cell volume, albumin, white blood cell count, and urea, indicative of its protective effect against hemo-, immuno- and nephrotoxicity of DDVP. Conclusion: N. sativa (Black Caraway) oil might be a potential antidote in hematotoxicity, immunosuppression and renal dysfunction in organophosphate poisoning, especially dichlorvos. The protective effect of NSO against dichlorvos toxicity can be attributed to its antioxidant capacity.

Objectives: Organophosphate (OP) pesticides inhibit both red blood cell (RBC) and plasma cholinesterases (ChEs). Oximes, especially pralidoxime (2-PAM), are widely used as antidotes to treat OP poisoning. In addition, N-acetylcysteine (NAC) is sometimes used as an adjuvant antidote. The current study aimed to assess the feasibility of using NAC as a single therapeutic agent for OP poisoning in comparison to in vitro 2-PAM. Methods:This study was carried out at the Razi Drug Research Center of Iran University of Medical Sciences, Tehran, Iran, between April and September 2014. A total of 22 healthy human subjects were recruited and 8 mL citrated blood samples were drawn from each subject. Dichlorvos-inhibited blood samples were separately exposed to low and high doses (final concentrations of 300 and 600 μmol.L-1, respectively) of 2-PAM, NAC and cysteine. Plasma and RBCs were then separated by centrifugation and their ChE activity was measured using spectrophotometry. Results: Although cysteine—and not NAC—increased the ChE activity of both plasma and RBCs over those of dichlorvos, it did not increase them over those of a high dose of 2-PAM. Conclusion:These results suggest that the direct reactions of 2-PAM and cysteine with dichlorvos and the reactivation of phosphorylated ChEs occurr via an associative stepwise addition-elimination process. High therapeutic blood concentrations of cysteine are needed for the elevation of ChE activity in plasma and RBCs; however, both this agent and NAC may still be effective in the reactivation of plasma and RBC ChEs.

Introduction: Atropine is not recommended in organophosphorus (OPs) poisoning cases without any obvious clinical signs. This study aimed to evaluate the clinical utility of Atropine challenge test in screening OPs poisoning cases with atypical presentation. Methods: In this prospective cross sectional study, after primary supportive care, patients with atypical pretentions of OPs poisoning underwent Atropine challenge test (1 mg intravenously) and demographic parameters, clinical presentations, and serum level of cholinesterase enzyme were compared between cases with positive and negative test results. Results: 20 patients with the mean age of 47.60 ± 13.25 years were studied. The mean time since exposure and initial symptoms was 6.17 ± 2.99 hours. The most common clinical presentations were tachycardia (55%) and flushing (35%). The atropine challenge test was positive in 3 (15.00%) cases. The two groups were the same regarding gender distribution (p = 0.582), mean age (p = 0.957), clinical presentation (p > 0.05), and mean PR interval (p = 0.729). The level of cholinesterase was 220.00 ± 15.52 U/mL and 332.17 ± 143.99 U/mL in patients with positive and negative Atropine challenge test, respectively (p = 0.006). Conclusion: Patients with positive Atropine challenge test had a significantly lower level of serum cholinesterase and response to Atropine in their therapeutic management. Hence, Atropine challenge test could be considered as a useful clinical test in the setting of acute OPs poising.