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In acute organophosphorus (OP) or carbamate poisoning, some patients require high dose atropine to counteract the effects on heart rate (HR) and blood pressure (BP). This study describes the factors associated with high dose atropine therapy and the use of adrenaline to reverse the inadequate HR response to atropine.Consecutive patients admitted to the intensive care unit (ICU) were prospectively recruited. Demographic data, treatment and outcomes of patients who failed to achieve target HR (100/min) or systolic BP90 mm Hg with either a cumulative atropine dose of 100-mg within 6-h following admission or an infusion of 30 mg/h for at least 3-h were compared with patients who achieved the targets. Factors associated with high dose atropine therapy were explored using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CIs).Of the 181 patients admitted with OP or carbamate poisoning, 155 patients fulfilled inclusion criteria. The mean (SD) age was 35.7 (15.8) years; admission APACHE-II score was 14.6 (7.5). Heart rate and/or BP target was not achieved in 13.6%. In these patients, target HR was achieved after adding adrenaline infusion at 2-4 μg/min. Ventilation duration (11.6 ± 6.3 vs. 8.4 ± 6.9 days,High dose atropine therapy is required in a subset of patients with OP and carbamate poisoning and was associated with longer ventilation duration and ICU stay. Adrenaline infusion improved hemodynamics in these patients.

Organophosphorus agents (OP) are widely used as pesticides due to their cost effectiveness, yet they present a significant public health risk owing to their high toxicity, especially in cases of occupational exposure in agriculture, during suicide attempts using pesticides, and as nerve agents in warfare. Their vigorous permeability through inhalation, ingestion, and dermal exposure results in a high number of reported OP poisoning cases and alarming mortality rates. Initial first-aid management involves decontamination, ventilation, and hemodialysis. Additionally, current treatment guidelines recommend prompt administration of atropine as a first-line antidote, oximes as a follow-up, benzodiazepines for seizure control, and pyridostigmine for prophylaxis. Nevertheless, current treatment options are associated with several challenges. Thus, recent research has focused on investigating novel approaches for their potential in improving current management strategies. This article intends to review recent advances in OP poisoning treatment, including agents investigated for their use as an alternative or adjunctive therapy, novel formulations such as nasal drops or sublingual tablets for emergency administration of atropine, as well as innovative strategies for enhanced oximes delivery and overall efficacy. However, two major barriers may limit these innovations, ethical issues associated with their clinical assessment in emergencies, and limited profitability in countries where most cases occur.

Despite organophosphate pesticide is the most prevalent cause of acute poisoning in low- and middle-income countries, data on organophosphate induced delayed neuropathy (OPIDN) are limited. We aimed to characterize organophosphates' long-term effects on the peripheral nervous system after an acute cholinergic crisis in adults.We performed a prospective observational study in an academic hospital of north India in patients aged 13-40 years with acute organophosphate ingestion. After resolving the cholinergic crisis, the patients were followed for six months with neurologic assessments, including history, neurologic examination, and nerve conduction study (NCS).Twenty-three patients were recruited to the study. All but one had normal neurological examination and NCS at discharge from hospital a median duration of six days (interquartile range, 3-10) after self-poisoning. Eight (34.8%) developed OPIDN during the six-month follow-up. Three patients had symptomatic neuropathy, and NCS detected subclinical peripheral nerve involvement in five. All cases were associated with chlorpyrifos ingestion (8/17 total chlorpyrifos cases). Two OPIDN cases had foot drop and gait ataxia at three-month which persist at six-month. One patient had distal paresthesia at three months, which improved at a six-month follow-up. NCS in OPIDN cases invariably revealed axonal degeneration, injury to motor fibers more than sensory fibers, and frequent peroneal nerve involvement. None of the baseline characteristics, including the ingested amount, predicted clinical or subclinical OPIDN in chlorpyrifos self-poisoned patients on a univariant analysis.Peripheral nerve involvement is not uncommon after recovery from a cholinergic crisis in chlorpyrifos self-poisoning and debilitating in some patients. Detection of subclinical injury on NCS may provide an early window to prevent severe symptomatic neuropathy.

International audience; Novel 6-alkyl- and 6-alkenyl-3-fluoro-2-pyridinaldoximes have been synthesised by using a mild and efficient chemoselective hydrogenation of 6-alkynyl-3-fluoro-2-pyridinaldoxime scaffolds, without altering the reducible, unprotected, sensitive oxime functionality and the C-F bond. These novel 6-alkyl-3-fluoro-2-pyridinaldoximes may find medicinal application as antidotes to organophosphate poisoning. Indeed, one low-molecular-weight compound exhibited increased affinity for sarin-inhibited acetylcholinesterase (hAChE) and greater reactivation efficiency or resurrection for sarin-inhibited hAChE, compared with those of 2-pyridinaldoxime (2-PAM) and 1-({[4-(aminocarbonyl)pyridinio]methoxy}methyl)-2-[(hydroxyimino)methyl]pyridinium chloride (HI-6), two pyridinium salts currently used as antidote by several countries. In addition, the uncharged 3-fluorinated bifunctional hybrid showed increased in vitro blood-brain barrier permeability compared with those of 2-PAM, HI-6 and obidoxime. These promising features of novel low-molecular-weight alkylfluoropyridinaldoxime open up a new era for the design, synthesis and discovery of central non-quaternary broad spectrum reactivators for organophosphate-inhibited cholinesterases.

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%) 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.

High lethality, fast action, and simple synthesis make nerve agents (NAs) the most dreaded chemical weapons (CWs) of mass destruction in the world. Disturbances of the autonomic nervous system and neuromuscular junction (NMJ) by NAs and organophosphorus (OP) insecticides lead to cholinergic crisis and skeletal muscle paralysis. Current medical intervention has remained mostly unchanged since their first discovery in the 1950s. Within this overview, we have followed their development, clinical successes, and failures and discuss the major demerits of available antidotes. In current times, with precision medicine becoming increasingly relevant in various fields of medicine, the antidotal approach should be broadened to better cope with individual cases of NA intoxication. When possible, countermeasures could be targeted directly to achieve a better patient prognosis. As the threat of NA misuse and accidental cases of OP insecticide intoxication are still omnipresent, advancement of intervention expertise and further research in this field should be supported.

INTRODUCTION: Atropine sulfate is an FDA-approved medical countermeasure (MCM) for the treatment of organophosphorus nerve agent and organophosphate pesticide toxicity. Sufficient MCM supplies must be available in an incident involving a mass human exposure either from an accidental chemical release or a terrorist attack. METHODS: We performed a randomized, 3-sequence, 3-period phase I crossover study to assess the bioavailability and pharmacokinetics (PK) of a single dose (0.5 mg and 1.0 mg) of 1% ophthalmic atropine sulfate solution administered sublingually to 15 healthy adult volunteers. The primary endpoint was evaluation of the bioavailability of each of the two sublingual doses against a 1.0 mg reference intravenous (IV) atropine dose. Secondary endpoints included the safety and tolerability (xerostomia scale) of atropine sulfate administered sublingually. RESULTS: Sublingual atropine was safe (no severe AEs or SAEs were reported with either dose) and well tolerated, with a single subject reaching maximum xerostomia on a single dosing day. The geometric mean AUC(∞) was 286.40, 493.81, and 816.47 min*ng/mL for the 0.5 mg and 1.0 mg sublingual doses, and the 1.0 mg IV dose, respectively. Compared to IV administration, the 1.0 mg sublingual dose produced 0.60 (90% CI: 0.55–0.66) of the overall concentration of atropine over time (AUC(∞)). CONCLUSION: Sublingual atropine sulfate 1% ophthalmic solution may be an alternative formulation and route of administration combination which expands the capacity and dosing options of atropine as a nerve agent MCM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13181-021-00873-0.

Organophosphates (OPs) are commonly used pesticides worldwide. Humans are exposed to OPs via different routes viz., the respiratory tract, gastrointestinal tract, and dermal integuments. OPs induce neuropathy by either phosphorylating acetyl cholinesterase or neuropathy target esterase, or by binding specifically to nicotinic or muscarinic receptors of nervous system. Other than neurobehavioral effects in humans, OPs cause cholinergic crisis, intermediate syndrome, OP-induced delayed neuropathy, and Chronic organophosphate-induced neuropsychiatric disorders in time and dosage dependent manner. Biomonitoring of OP markers from body fluids minimizes or measures the severity of the impact, allowing for timely control of the exposure. The standard treatments for OPs poisoning which avoid secondary organ damage are atropine administration, acetylcholine esterase restoration therapy with oximes, and general intensive care. This review summarizes the toxic manifestation data available on humans and discusses potential therapeutic modalities, with the aim to highlight the importance of increasing awareness about its potential risk and reevaluation of exposure level.

Acute organophosphorus pesticide poisoning (AOPP) with cardiac arrest has an extremely high mortality rate, and corresponding therapeutic strategies have rarely been reported. Therefore, this study aimed to explore the prognostic factors and effective treatments of AOPP-related cardiac arrest. This retrospective study was conducted in our department in the years 2018–2021. We conducted a descriptive analysis of the clinical manifestations, rescue strategies, and prognosis of patients with AOPP who had experienced cardiac arrest and successful cardiopulmonary resuscitation. This study included six cases of patients with AOPP in addition to cardiac arrest; in four cases, cardiac arrest occurred

Organophosphorus (OP) insecticide poisoning causes respiratory failure due to acetylcholinesterase (AChE) inhibition. The AChE reactivating antidote pralidoxime was developed in the 1950s and was soon noted to benefit patients occupationally poisoned with the highly potent OP insecticide parathion. Routine use of pralidoxime and other oximes such as obidoxime then became widely recommended. However, nearly all severe cases of OP poisoning now result from self-poisoning with large volumes of less potent (WHO hazard class Ib and II) insecticides and co-formulated solvents. Unfortunately, oxime clinical trials have never shown benefit from their use for these patients, and some have shown that pralidoxime may be associated with harm, including increased mortality. Oximes should not be used routinely for the care of OP insecticide-poisoned patients until translational and clinical studies have identified a safe and effective oxime regimen and identified the patients who benefit.

The role of soluble growth stimulating gene 2 protein and highly sensitive cardiac troponin in the diagnosis of early myocardial injury caused by acute organophosphorus pesticide poisoning was studied. 171 inpatients with AOPP were divided into three experimental groups according to their mild, moderate, and severe conditions. 20 healthy people were selected as the control group. The levels of cTnI, HS-CTNI, NT proBNP, and ST2 were measured at the 4th and 12th hours after the experiment. The measured data were expressed by mean standard deviation. The independent sample t -test was used for the detection between the two groups, and one-way ANOVA was used for the analysis and comparison between multiple groups. The relevant data were analyzed by Spearman correlation test ( P < 0.05 ). The levels of cTnI and HS cTnI in the experimental group increased with the extension of time and the deepening of poisoning degree; four hours after admission, ST2 and NT proBNP water in the control group and the experimental group increased significantly on average. According to the analysis of the data, there was a positive correlation between HS TnI and ST2 in patients with AOPP ( r = 0.938 , P < 0.001 , r = 0.827 , P < 0.001 ). The more serious the disease, the higher the concentrations of HS TnI and ST2, and the more serious the myocardial injury.

Introduction: Patients who require mechanical ventilation after self-poisoning with ingested organophosphorus (OP) insecticides often die. Aspiration of stomach contents may contribute to lung injury and lethality. This study was designed to assess the severity of direct and indirect pulmonary injury created by pulmonary instillation of mixtures of OP insecticide, solvent (Solv), and porcine gastric juice (GJ), compared to controls.Methods: Terminally anaesthetised minipigs (groups n=5) were exposed to sham bronchoscopy or given mixtures (0.5mL/kg) of: saline, GJ, OP insecticide and GJ (OP+GJ), or Solv and GJ (Solv+GJ), placed into the right lung, and monitored for 48h. Lung injury was assessed through analysis of bronchoalveolar lavage fluid (BALF), computed tomography and histopathology.Results: OP+GJ created a direct lung injury consisting of neutrophil infiltration, oedema and haemorrhage, as well as indirect injury to the other lung. OP+GJ directly-injured lung parenchyma had increased concentrations of BALF protein, albumin, IL-6, IL-8 and C-reactive protein (CRP) at 24h (PConclusion: Pulmonary instillation of OP+GJ created more lung damage than controls or Solv+GJ. In patients with severe OP insecticide poisoning and reduced consciousness, early airway protection is likely to reduce pulmonary damage.

Therapeutic efficacy of antidotal treatment of acute poisoning by nerve agents is generally assessed by the evaluation of LD50 values of nerve agents over 24 h following poisoning without or with a...

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.

Background: Nowadays, organophosphate (OP) compounds are widely used in agricultural field as an insecticide. Toxicity with these compounds is owing to inhibition of acetyl cholinesterase enzyme. Patients are presented with muscarinic and nicotinic side effects. Objective: To study the clinical aspect of OP poisoning in detail with hospital stay, clinical course, complication, and recovery and mortality in OP poisoning. Materials and Methods: This study was done at GGH, Vijayawada India, comprising 250 cases of OP poisoning. After taking written consent, personal history of the patients was taken. Then, a detailed history regarding poison and clinical symptoms was taken. Then, general and systematic examinations of patients were carried out, and blood samples were sent for investigations. We followed up the patients till discharge or death. Result: In our study, maximum incidence of OP poisoning was in between 21-30 years age group (37.5%), and male to female ratio was 4:1. Clinical symptoms such as unconsciousness, stupor (75%), vomiting (10%), convulsions (62.5%) are froth at mouth and nostrils (50%) and the common symptoms whereas constricted pupils (75%), pulmonary oedema (87.5%), Tachycardia (75%), hypotension (25%) are the common signs noted in this series of cases who were treated in the hospital and where the hospital records were available. Histopathological examination of tissue revealed usually congestion of brain, oedema and congestion of lungs and fatty degeneration in liver and in some cases cloudy swelling and tubular necrosis in kidneys Conclusion: Detailed history and thorough clinical examination of patients are helpful in diagnosing the patients of OP poisoning. Life-threatening complications occurred in these patients. Early detection and immediate treatment in intensive care units with injections atropine and PAM can increase the chances of survival rate of patients.

Some epidemiological evidence implicates acute organophosphate (OP) pesticide poisoning in long-term neurocognitive deficits. However, no study has prospectively followed up poisoned patients long-term from the time of intoxication. We aimed to determine whether clinically significant acute OP self-poisoning leads to subacute and chronic neurocognitive deficits, in a prospective follow up study.Employing Mini Mental State Examination, Digit Span and Cambridge Neuropsychological Test Automated Battery (CANTAB), we compared multiple cognitive functions in 222 patients hospitalized with acute OP pesticide self-poisoning with a control group of 52 patients hospitalized with paracetamol overdose, at three time points: on discharge following clinical recovery, 6 weeks and 6 months post-ingestion. Intergroup comparisons at each time point were done in multiple regression models, adjusting for sex, age, education and psychiatric comorbidities. OP within-group analysis was done to determine a dose-response relationship.After adjusting for covariates, the OP poisoned group had significantly poorer working memory (Digit Span) and episodic memory (CANTAB Paired Associates Learning); impaired spatial planning (CANTAB Stocking of Cambridge); and slower response speed in the sustained attention task (CANTAB Rapid Visual Information Processing), in the post-discharge assessment. Only working memory and episodic memory measures were impaired in the OP group at 6 weeks, whereas no significant intergroup differences were observed at 6 months. The OP subgroup who had complete red cell acetylcholinesterase inhibition on admission had poorer episodic memory when tested post-discharge than those who had partial inhibition, but no significant subgroup differences were observed at 6 weeks or 6 months.Acute OP pesticide poisoning may cause neuropsychological impairment that outlasts the cholinergic phase on a subacute time scale; but does not cause measurable chronic neuropsychological deficits.

Background: Individuals have the chance to get exposed to organophosphates either at domestic, or industrial spheres. Organophosphate poisoning is a worldwide problem. Organophosphate insecticides inhibit Cholinesterase enzymatic activity. Chlorpyrifos, Phorate 10% granules and Monocrotophos are insecticides and pesticides commonly used in India by farmers. Aim: The present study aims at determining the effect oforganophosphate compounds on thyroid profile in individuals exposed to acute poisoning. Materials and Methods: In this study, those individuals who were acutely presented at the emergency department, SVS Medical College, Mahabubnagar, with a history of intentional or accidental intake of either chlorpyrifos or Phorate 10% granules or Monocrotophos (Organophosphorus compounds) were taken as cases. Intake of these compounds was confirmed by analyzing serum cholinesterase levels. Those patients having a serum cholinesterase levels value below 4000 U/L were included in this study. Simultaneously, the sample was analyzed for thyroid profile that includes Total triiodothyronine (TT3), Total tetraiodothyronine (TT4) and Thyroid stimulating hormone (TSH). Reanalyzing of thyroid profile was done after a time gap of one month from the day of discharge from hospital after recovery. Results: Total T3, Total T4 and TSH values showed statistically significant change (p-value between the acute poisoning phase and one month follow up phase of after recovery. Conclusion: Total T4 values are significantly higher in acute organophosphorus poisoned phase mimicking thyrotoxicosis, and return to normal biological reference range after recovery, whereas TSH values in acute opiates poisoned phase were significant lower than that of recovery phase. Keywords: Organophosphorus compounds (OPC), Total triiodothyronine(TT3), Total tetraiodothyronine(TT4), Thyroid stimulating hormone (TSH), Cholinesterase enzyme.

Organophosphorus (OP) insecticide poisoning is a significant health problem in South Asian countries. Although cholinergic receptors are present at the junction between photoreceptors and the retinal pigment epithelium (RPE), human studies of the effects of OP poisoning on the visual pathways are very few. This study aims to demonstrate the pattern of changes in retina and post retinal pathways in patients with acute OP poisoning using visual electrophysiological tests.This is an observational, cross-sectional study conducted at the Neurophysiology Unit, Teaching Hospital, Peradeniya, Sri Lanka. We tested 16 patients recovered from cholinergic phase, at least 24 h after deatropinization and within 8 weeks of OP ingestion. We assessed the functional integrity of the photoreceptors and ganglion cells of the macula by pattern electroretinography (PERG); RPE by electro-oculography (EOG); and post retinal pathways by pattern reversal visual evoked potentials (PR-VEP). Latencies and amplitudes of PR-VEP and PERG, light peak (LP), dark trough (DT) and Arden ratio of EOG were determined in patients and compared with 16 controls using the Mann-Whitney U test.Of the 16 OP-poisoned patients (median age of 37 ± IQR 20 years), six (37.5%) had reduced Arden ratio with reference to the International Society of Clinical Electrophysiology of Vision cut-off value of 1.7. The median Arden ratio in patients (1.69 ± IQR 0.36) was significantly lower compared to controls (1.90 ± IQR 0.4). The median latencies and amplitudes of PR-VEP or PERG were not significantly different between patients and controls. However, three patients had prolonged P100 latencies in PR-VEP and one had prolonged P50 latency in PERG.Acute OP poisoning seems to affect the functions of the RPE and the visual electrophysiological changes outlast the cholinergic phase. Limited evidence suggests that photoreceptors of the macula region and post retinal pathway might be affected in some patients.

Organophosphorus (OP) pesticides and nerve agents still pose a threat to the population. Treatment of OP poisoning is an ongoing challenge and burden for medical services. Standard drug treatment consists of atropine and an oxime as reactivator of OP-inhibited acetylcholinesterase and is virtually unchanged since more than six decades. Established oximes, i.e. pralidoxime, obidoxime, TMB-4, HI-6 and MMB-4, are of insufficient effectiveness in some poisonings and often cover only a limited spectrum of the different nerve agents and pesticides. Moreover, the value of oximes in human OP pesticide poisoning is still disputed. Long-lasting research efforts resulted in the preparation of countless experimental oximes, and more recently non-oxime reactivators, intended to replace or supplement the established and licensed oximes. The progress of this development is slow and none of the novel compounds appears to be suitable for transfer into advanced development or into clinical use. This situation calls for a critical analysis of the value of oximes as mainstay of treatment as well as the potential and limitations of established and novel reactivators. Requirements for a straightforward identification of superior reactivators and their development to licensed drugs need to be addressed as well as options for interim solutions as a chance to improve the therapy of OP poisoning in a foreseeable time frame.

Pulmonary delivery of protein drugs into the systemic circulation is highly desirable as the lung provides a large absorption surface area and a more favorable environment for biologics compared to other delivery routes. However, pulmonary systemic delivery of proteins presents several challenges such as poor protein stability and limited bioavailability, especially for large proteins (molecular weight > 50 kDa), which exhibit an average bioavailability of 1% to 5% when delivered via the pulmonary route. Here, we demonstrated that with the conjugation of zwitterionic poly(carboxybetaine) (pCB) polymer, the bioavailability of organophosphate hydrolase (OPH) was significantly increased from 5% to 53%. OPH conjugated with pCB delivered through intubation-assisted intratracheal instillation (IAIS) into the lung exhibited improved pharmacokinetic properties and prophylactic efficacy against organophosphate poisoning, showing its application potential. Zwitterionic polymer conjugation provides the possibility for a favorable, non-invasive delivery of biological therapeutics into the systemic circulation.

Aims: The present study aims to determine the phototoxic and haemolytic activity of organophosphorus. The use of alternative in vitro assays with human erythrocytes is suggested to predict the polluting effect of these products on health. Methodology: Human erythrocytes from Toluca Blood Bank were used. Sodium dodecyl sulfate was employed as a positive control. Additionally, the haemolysis percentage of three organophosphate (Acetate, Chlorpyrifos, Malathion, Methamidophos, Methyl Parathion) induced photo haemolysis formulated with surfactants on a concentration of 2 x 109 erythrocytes were evaluated. Finally, the products were classified as irritant or phototoxic. Results: Results showed that the HC50 red blood cells were similar for each organophosphate (Malathion and Methamidophos) indicating very irritant action with ratio classification (L/D) of 0.041 and 0.053, respectively. On the other hand, Chlorpyrifos was classified as an irritant with L/D= 0.14. On the other hand, the HC50 obtained photo hemolysis assays irradiated red blood cells was similar for each organophosphate (Acetate, Chlorpyrifos, Malathion, Methamidophos, Methyl Parathion) indicating no phototoxic action. Conclusion: As a conclusion, it can be said that the parameters of haemolysis and denaturation of proteins are good indicators to classify organophosphorus formulated with surfactants as irritating or phototoxic.

Introduction: Acute organophosphorus (OP) pesticide poisoning is widespread in the developing world. Being predominantly an agricultural country, pesticides and insecticides are used abundantly for cultivation, and access to these poisonous chemical substances by the population is easy. The objectiveof the study was to identifythe nature of the demographic profile, type of compound, clinical manifestations, and outcome of organophosphate poisoning presenting to a tertiary care teaching hospital in India. Material and methods: A cross-sectional study was conducted among 100 patients admitted with OPC poisoning inthe department of general medicine,Velammal Medical College Hospital and Research Institute, Madurai from January 2016 to July 2019. The diagnosis was made based on history or evidence of exposure to OP compound within 24 hours; characteristic manifestations of OP poisoning include, miosis, fasciculations, excessive salivation, improvement of signs and symptoms with administration of atropine were recorded. IBM SPSS version 22 was used for statistical analysis. Results:The majority of the subjects were males(80%). The majority (66%) were in the age group of 21-40 years. The most common OPC to be consumed was Methyl parathion (27%), followed by chlorpyrifos (22%). The major GIT complications were abdominal pain/cramps (100%), followed by nausea and vomiting (83%). Mechanical ventilation was needed in 40% and mortality was reported in 25% of the subjects. Conclusion:OP poisoning affects resonantly males in their economically productive phase of life. Considering the high mortality, adequate strengthening of health services, especially at the primary level is the need of the hour.

Patients intoxicated with organophosphorous compounds may need general anaesthesia to enable mechanical ventilation or for control of epileptiform seizures. It is well known that cholinergic overstimulation attenuates the efficacy of general anaesthetics to reduce spontaneous network activity in the cortex. However, it is not clear how propofol, the most frequently used intravenous anaesthetic today, is affected. Here, we investigated the effects of cholinergic overstimulation induced by soman and acetylcholine on the ability of propofol to depress spontaneous action potential activity in organotypic cortical slices measured by extracellular voltage recordings. Cholinergic overstimulation by co-application of soman and acetylcholine (10 μM each) did not reduce the relative inhibition of propofol (1.0 μM; mean normalized action potential firing rate 0.49 ± 0.06 of control condition, p < 0.001, Wilcoxon signed rank test) but clearly reduced its efficacy. Co-application of atropine (10 nM) did not improve the efficacy. Propofol preserved its relative inhibitory potential but did not produce a degree of neuronal depression which can be expected to assure hypnosis in humans. Since a combination with atropine did not improve its efficacy, an increase in dosage will probably be necessary when propofol is used in victims suffering from organophosphorous intoxication.

Background 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.

Organophosphorus (OP) 1 nerve agents pose a severe toxicological threat, both after dissemination in military conflicts and by terrorists. Hydrolytic enzymes, which may be administered into the blood stream of victims by injection and can decompose the circulating nerve agent into non-toxic metabolites in vivo, could offer a treatment. Indeed, for the phosphotriesterase found in the bacterium Brevundimonas diminuta (BdPTE), 2 engineered versions with improved catalytic efficiencies have been described; yet, their biochemical stabilities are insufficient for therapeutic use. Here, we describe the application of rational protein design to develop novel mutants of BdPTE that are less susceptible to oxidative damage. In particular, the replacement of two unpaired cysteine residues by more inert amino acids led to higher stability while maintaining high catalytic activity towards a broad spectrum of substrates, including OP pesticides and V-type nerve agents. The mutant BdPTE enzymes were produced in Escherichia coli, purified to homogeneity, and their biochemical and enzymological properties were assessed. Several candidates both revealed enhanced thermal stability and were less susceptible to oxidative stress, as demonstrated by mass spectrometry. These mutants of BdPTE may show promise for the treatment of acute intoxications by nerve agents as well as OP pesticides.

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.

Organophosphate pesticide poisoning is a common clinical problem in developing countries, bringing with it significant morbidity and mortality. There is limited evidence on the mobility status in patients who survive acute intoxication by organophosphates. The purpose of this study is to assess the mobility patterns and barriers to mobilization in organophosphate poisoning survivors in the intensive care unit. This cross-sectional study looked at 37 patients with acute intoxication from organophosphate compounds. Patients with Acute Physiology and Chronic Health Evaluation scores of less than 93 and Richmond Agitation and Sedation scores between −2 and +2 were included. Potential mobility barriers, bed mobility, functional strength, transfers, and endurance were assessed using the Perme Intensive Care Unit Mobility score on alternative days for the first ten days of intensive care unit admission. Perme scores (2.50–6.0, p ≤ 0.01) improved significantly with improvement in the subcomponents of bed mobility score (1.83 ± 0.35 to 7.23 ± 3.84), transfers (0.37 ± 0.02 to 4.78 ± 3.84), and gait (1.83 ± 0.35 to 5.23 ± 1.27) from day 2 through day 10 of hospital admission. The endotracheal tube and continuous infusion were identified as major barriers to mobilization (66.6%) using Perme scores. Perme scores improved gradually in organophosphate poisoning patients in the intensive care unit. Identification of mobility barriers may help in the modification of rehabilitation goals.

Introduction: Acute organophosphate (OP) poisoning is a global health problem and responsible for many deaths worldwide every year. It acts by inhibition of acetylcholinesterase causing cholinergic crises that lead to muscarinic, nicotinic and central manifestations. One of the most serious complications of organophosphate exposure is cardiac toxicity including electrocardiogram changes.This study aimed to evaluate corrected QT interval as predictor of major outcome events which included mortality, need for mechanical ventilation, number of atropine and toxogonine ampoules and duration of hospital stay in acute organophosphate toxicity. Methods: The study recruited 98 patients suffering from acute OP poisoning, who were admitted to Tanta University Poison Control Unit. QTc interval length and the different outcomes of the patients were recorded. Results: Fifty five patients (56.1 %) showed a prolonged QTc interval. Significant statistical association was recorded between QTc interval and delay time, manner & route of poisoning, severity of oranophosphrous toxicity and pseudocholinesterase level. Also, significant statistical association was recorded between QTc interval and need for mechanical ventilation, mortality, number of atropine & toxogonine ampoules and duration of hospital stay. Conclusion: Finally, it was concluded that QTc interval could be a good predictor for outcomes of acute organophosphrous poisoning.

Introduction First responders and those who work with organophosphate (OP) compounds can experience ocular symptoms similar to those caused by exposure to low levels of nerve agents. This study was designed to examine the efficacy of a safe, clinically available, simulant that reproduces ocular symptoms associated with low-level OP exposure. Among these ocular symptoms are a constriction of the pupils (miosis), decreased visual acuity, and changes in accommodation. Materials and Methods Volunteers aged 18–40 were assigned to groups receiving either a two-drop or three-drop dose of FDA approved 2% pilocarpine ophthalmic solution. Baseline visual performance measurements were taken before eye drop instillation and a timer was started following the first drop of pilocarpine. Once eye drops were administered, visual performance including distant and near vision, pupil size, and accommodation were measured every 5 minutes for 2 hours. Results Both groups experienced significant miosis in excess of 90 minutes. Visual acuity was significantly reduced because of accommodative changes. The three-drop group experienced longer lasting combined effects when compared to the two-drop group. Conclusions 2% pilocarpine ophthalmic solution can safely simulate major ocular symptoms of OP exposure for behavioral research studies for at least 60 minutes.