Fenitrothion (Sumithion) Poisoning-Related Fasciculations Successfully Managed With Levetiracetam: A Case Report.

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.

Cholesterol Oxime Olesoxime Assessed as a Potential Ligand of Human Cholinesterases.

Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood-brain barrier, and has demonstrated excellent safety and tolerability properties in clinical research. These characteristics indicate it may serve as a centrally active ligand of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), whose disruption of activity with organophosphate compounds (OP) leads to uncontrolled excitation and potentially life-threatening symptoms. To evaluate olesoxime as a binding ligand and reactivator of human AChE and BChE, we conducted in vitro kinetic studies with the active metabolite of insecticide parathion, paraoxon, and the warfare nerve agents sarin, cyclosarin, tabun, and VX. Our results showed that both enzymes possessed a binding affinity for olesoxime in the mid-micromolar range, higher than the antidotes in use (i.e., 2-PAM, HI-6, etc.). While olesoxime showed a weak ability to reactivate AChE, cyclosarin-inhibited BChE was reactivated with an overall reactivation rate constant comparable to that of standard oxime HI-6. Moreover, in combination with the oxime 2-PAM, the reactivation maximum increased by 10-30% for cyclosarin- and sarin-inhibited BChE. Molecular modeling revealed productive interactions between olesoxime and BChE, highlighting olesoxime as a potentially BChE-targeted therapy. Moreover, it might be added to OP poisoning treatment to increase the efficacy of BChE reactivation, and its cholesterol scaffold could provide a basis for the development of novel oxime antidotes.

Utility of Automated Infrared Pupillometry in Assessing the Prolonged Course of Organophosphate Poisoning: A Case Report.

Central and autonomic nervous system signs of organophosphate poisoning (OP), such as altered consciousness, noticeable lacrimation, and salivation, can be influenced by medications used in intensive care settings, such as atropine and pralidoxime methyl (PAM). Because of this, there are no established methods for assessing the duration of OP while receiving antidotal treatment. In the present case, we used the Neurological Pupil Index (NPi) to evaluate the duration of OP in an 82-year-old woman who attempted suicide by ingesting up to 100 mL of fenitrothion. Until hospitalization day (HD) 20, discontinuation of atropine led to the recurrence of altered consciousness, while its reinstatement resulted in improvement; this made it difficult to assess the prolongation of OP based on signs and symptoms. Until HD 20, the NPi remained at 0/0, and subsequently, it increased. Additionally, even after discontinuing atropine, consciousness, tearing, and salivation did not worsen, indicating recovery from OP. On HD 26, serum acetylcholinesterase (AChE) levels were elevated above the measurable level for the first time, following an increase in the NPi. In this case, assessing the persistence of OP based on signs was challenging because these signs improved with atropine and PAM treatment. The improvement in NPi levels coincided with an improvement in poisoning, suggesting that NPi is useful for evaluating the duration of OP. NPi is noninvasive and sensitive compared to AChE, which is used to gauge the persistence of OP and could be used to allow earlier cessation of medication and guide appropriate treatment durations.

Management of organophosphorus poisoning and the role of magnesium sulfate: A scoping review of literature.

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.

Navigating the Neurological Abyss: A Comprehensive Review of Organophosphate Poisoning Complications.

Organophosphate poisoning is a significant global health concern with implications for both occupational and environmental settings. This comprehensive review thoroughly explores the biochemical basis, clinical presentation, diagnostic methods, treatment strategies, and long-term effects of organophosphate exposure. The acute phase is characterized by cholinergic crisis, respiratory distress, and neurological manifestations, while delayed complications include the intermediate syndrome and organophosphate-induced delayed neuropathy. Diagnostic approaches involve clinical evaluation, cholinesterase-level assessments, and imaging studies. Treatment strategies encompass decontamination, antidotes such as atropine and pralidoxime, and supportive care. Long-term effects may include cognitive and neurological sequelae, necessitating rehabilitation approaches such as physical and occupational therapy. Prevention strategies include stringent occupational safety guidelines, sustainable agricultural practices, and public awareness initiatives. The implications for clinical practice underscore the importance of a multidisciplinary approach. At the same time, the call to action emphasizes the need for collaborative efforts in prevention and awareness to mitigate the impact of organophosphate poisoning on public health and the environment.

Tiger nut/coconut dietary intervention as antidotal nutritional remediation strategy against neurobehavioural deficits following organophosphate-induced gut-brain axis dysregulation in mice.

Organophosphate poisoning remains a global health crisis without efficacious treatments to prevent neurotoxicity. We examined whether antidotal tiger nut and coconut dietary intervention could ameliorate neurobehavioral deficits from organophosphate dichlorvos-induced gut-brain axis dysregulation in a mouse model. Mice were divided into groups given control diet, dichlorvos-contaminated diets, or dichlorvos plus nut-enriched diets. They were exposed to a DDVP-contaminated diet for 4 weeks before exposure to the treatment diets for another 8 weeks. This was followed by behavioural assessments for cognitive, motor, anxiety-, and depressive-like behaviours. Faecal samples (pre- and post-treatment), as well as blood, brain, and gut tissues, were collected for biochemical assessments following euthanasia. Dichlorvos-exposed mice displayed impairments in cognition, motor function, and mood along with disrupted inflammatory and antioxidant responses, neurotrophic factor levels, and acetylcholinesterase activity in brain and intestinal tissues. Weight loss and altered short-chain fatty acid levels additionally indicated gut dysfunction. However, intervention with tiger nut and/or coconut- enriched diet after dichlorvos exposure attenuated these neurobehavioral, and biochemical alterations. Our findings demonstrate organophosphate-induced communication disruptions between the gut and brain pathways that manifest in neuropsychiatric disturbances. Overall, incorporating fibre-rich nuts may represent an antidotal dietary strategy to reduce neurotoxicity and prevent brain disorders associated with organophosphate poisoning.

Resurgence to Life: A Case Report on Inpatient Rehabilitation in Organophosphate Poisoning Followed by Intermediate Syndrome.

Organophosphate poisoning (OPP) results from the occupational, accidental, or suicidal intake of organophosphate pesticides (OPs). There is a huge limitation in the available literature on OPP cases and the role of physiotherapy in such cases. We report a case of a 33-year-old farmer, found in a state of ingested insecticide and admitted to the emergency department. The patient had two to three episodes of vomiting, associated with continuous tremors in his hands and legs. Immediately infused with atropine, the patient's general condition deteriorated, and he was intubated with an endotracheal tube. With the signs of long-term intubation, a tracheostomy was done. A respiratory therapy consult was taken for indications of intermediate syndrome and to achieve early weaning. The patient's referral was received in view of the long-term requirement of bronchial hygiene and the need for early ambulation as well as psychological support. Informed consent was taken from the family prior to the commencement of the treatment. Respiratory therapy interventions included body positioning, bronchial hygiene techniques, chest proprioceptive neuromuscular facilitation (PNF) techniques, and mobility exercises to achieve early ambulation. Physiotherapists have the appropriate training, knowledge, and skills to deliver the exercise components and help patients return to their activities of daily living. Significant levels of improvement have been seen in the general condition of the patient. The overall functioning of the patient's health was seen as improved on the scales of consciousness, early mobility in the step-down unit, and quality of life.

Tuning the Envelope Structure of Enzyme Nanoreactors for In Vivo Detoxification of Organophosphates.

Encapsulated phosphotriesterase nanoreactors show their efficacy in the prophylaxis and post-exposure treatment of poisoning by paraoxon. A new enzyme nanoreactor (E-nRs) containing an evolved multiple mutant (L72C/Y97F/Y99F/W263V/I280T) of Saccharolobus solfataricus phosphotriesterase (PTE) for in vivo detoxification of organophosphorous compounds (OP) was made. A comparison of nanoreactors made of three- and di-block copolymers was carried out. Two types of morphology nanoreactors made of di-block copolymers were prepared and characterized as spherical micelles and polymersomes with sizes of 40 nm and 100 nm, respectively. The polymer concentrations were varied from 0.1 to 0.5% (w/w) and enzyme concentrations were varied from 2.5 to 12.5 µM. In vivo experiments using E-nRs of diameter 106 nm, polydispersity 0.17, zeta-potential -8.3 mV, and loading capacity 15% showed that the detoxification efficacy against paraoxon was improved: the LD50 shift was 23.7xLD50 for prophylaxis and 8xLD50 for post-exposure treatment without behavioral alteration or functional physiological changes up to one month after injection. The pharmacokinetic profiles of i.v.-injected E-nRs made of three- and di-block copolymers were similar to the profiles of the injected free enzyme, suggesting partial enzyme encapsulation. Indeed, ELISA and Western blot analyses showed that animals developed an immune response against the enzyme. However, animals that received several injections did not develop iatrogenic symptoms.

Suspected intermediate syndrome in a dog after organophosphate poisoning.

OBJECTIVE: To discuss the clinical presentation and successful treatment of a suspected case of intermediate syndrome due to organophosphate (OP) poisoning in a dog. CASE SUMMARY: Two dogs presented with acute cholinergic signs after ingesting an OP insecticide containing 50% acephate. Clinical signs consistent with acute cholinergic crisis resolved in both dogs within 24 hours postingestion. One dog developed an onset of neurological signs consistent with intermediate syndrome approximately 24 hours postingestion. This patient's clinical signs resolved with the use of pralidoxime chloride. NEW OR UNIQUE INFORMATION PROVIDED: OP poisoning most commonly presents as an acute cholinergic crisis, with rare instances of animals developing intermediate syndrome. Few reports of successful treatment and recovery from intermediate syndrome exist in the veterinary literature, particularly with instances in which 2 dogs within the same exposure setting were treated for acute cholinergic signs and only 1 progressed to an intermediate syndrome. This report also highlights the importance of early intervention with pralidoxime chloride prior to the onset of aging.

Hyperlipasemia Sans Pancreatitis: A Case Series.

Acute pancreatitis results in inflammation and autodigestion of pancreatic acinar cells leading to the elevation of pancreatic enzymes, namely, amylase and lipase. Serum lipase levels have long been considered a hallmark of acute pancreatitis. However, pancreatitis is not always the cause of elevated serum lipase levels. This series presents four patients who had elevated serum lipase levels without any demonstrable damage to the pancreas on imaging. On further evaluation, one of the patients was found to have acute on chronic kidney disease (CKD) whose lipase levels settled later. A patient presenting with an episode of acute gastroenteritis, later diagnosed to have Crohn's disease, also had hyperlipasemia, which improved after a course of initial antibiotics. Non-gastrointestinal causes, such as lupus nephritis and organophosphate (OP) poisoning, also had elevated lipase levels on presentation, in which the hyperlipasemia settled with supportive treatments. It is important to remember other causes of elevated lipase levels in patients with a normal pancreas on imaging studies.

Conjugates of nucleobases with triazole-hydroxamic acids for the reactivation of acetylcholinesterase and treatment of delayed neurodegeneration induced by organophosphate poisoning.

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.

Outcome prediction using sequential organ failure assessment (SOFA) score and serum lactate levels in organophosphate poisoning.

Background: Organophosphorus compounds are widely used as pesticides in agriculture practicing countries like India. Since it is readily available and accessible, it is one of the most commonly used agents for suicidal poisoning. The current study was undertaken to evaluate the performance of the SOFA score (scoring system) and the serum lactate level (laboratory parameter) as a mortality predictor in organophosphorus poisoning. Material and Methods: This prospective observational study was conducted at AIIMS, Bhubaneswar, for 17 months. The study population included all patients with an alleged history of ingestion of organophosphorus (OP) compounds reporting to the casualty. The receiver operating characteristic (ROC) curve and the logistic regression analysis were used for the analysis. Results: In our study, 75 patients with OP poisoning were studied after satisfying the inclusion criteria. OP poisoning was commonly seen in married males aged 21-40 years. Twelve (16%) patients died during the process of treatment. There was a statistically significant difference in the mean SOFA score, serum lactate level, pH value, and mean duration of hospital stay between the discharged and the deceased patients. In the current study, the ROC curve analysis used to assess the predictor of the outcome of OP poisoning showed that the area under the curve for SOFA score and serum lactate level were 0.794 (95% CI 0.641-0.948) and 0.659 (95% CI 0.472-0.847), respectively. Conclusion: Sequential Organ Failure Assessment (SOFA) score is significantly associated with the outcome of organophosphate poisoning and can be utilized to predict mortality.

The role of a combination of N-acetylcysteine and magnesium sulfate as adjuvants to standard therapy in acute organophosphate poisoning: A randomized controlled trial.

Background: Mortality in acute organophosphate (OP) poisoning remains high despite current standard therapy with atropine and oximes. Due to dose-limiting side effects of atropine, novel therapies are targeting other putative mechanisms of injury, including oxidative damage, to reduce atropine dosage. Objectives: N-acetylcysteine (NAC) and magnesium sulfate (MgSO4) have different mechanisms of actions and should act synergistically in OP poisoning. In this study, we wanted to evaluate whether this novel combination, used as an adjuvant to standard care, could improve clinical outcomes. Methods: The study was conducted in the Emergency Department and ICU of AIIMS Bhubaneswar (a tertiary care center and government teaching institute) between July 2019 and July 2021. Eighty-eight adult patients with history and clinical features of acute OP poisoning were randomly allocated (1:1) into two groups. The Study group received 600 mg NAC via nasogastric tube thrice daily for 3 days plus a single dose of 4 g Inj. MgSO4 IV on first day and the Control group received suitably matched placebo (double-blinding) - in addition to standard care in both the groups. The primary outcome measure was to compare the total dose of Inj. Atropine required (cumulative over the entire treatment duration) between the control group and the study group receiving NAC and MgSO4. The secondary outcome measures were lengths of ICU and hospital stays, need and duration of mechanical ventilation, the differences in BuChE activity, oxidative stress biomarkers - MDA and GSH levels, the incidences of adverse effects including delayed sequalae like intermediate syndrome and OPIDN, and comparison of mortality between the two groups. Results: Data from 43 patients in Control and 42 patients in Study group was finally analyzed. The baseline parameters were comparable. Total atropine requirements were lower in the Study group [175.33 ± 81.25 mg (150.01-200.65)] compared to the Control [210.63 ± 102.29 mg (179.15-242.11)] [Mean ± SD (95% CI)], but was not statistically significant. No significant differences in any of the other clinical or biochemical parameters were noted. Conclusion: The N-acetylcysteine and MgSO4 combination as adjuvants failed to significantly reduce atropine requirements, ICU/hospital stay, mechanical ventilatory requirements, mortality and did not offer protection against oxidative damage.

Organophosphorus Poisoning: Acute Respiratory Distress Syndrome (ARDS) and Cardiac Failure as Cause of Death in Hospitalized Patients.

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.

Deltamethrin Poisoning Mimicking Organophosphate Poisoning: A Case Report.

Deltamethrin is a newer class of insecticide used on crops, pets, and livestock, in home pest control, and malaria vector control belonging to the synthetic pyrethroid group, which is being promoted in the place of organophosphate compounds due to the harmful and persistent effects of the latter. Unfortunately, as its usage increased, so has the number of poisoning cases associated with deltamethrin. Fortunately, the mortality in deltamethrin poisoning cases is low. However, deltamethrin poisoning causes signs and symptoms similar to the clinical features of organophosphate poisoning. This case report is of a 20-year-old man who consumed an unknown substance in a suicidal attempt and presented with clinical signs of organophosphate toxicity. Later the compound was identified as deltamethrin. This case report adds to the medical literature on deltamethrin poisoning. It showed that apart from the similarity in their clinical features in toxicity, deltamethrin can even give a positive result on atropine challenge tests like organophosphate and that the fasciculations induced by deltamethrin may be temporary. This case report will also benefit the clinician in unknown compound poisoning cases as it shows that the clinician can suspect deltamethrin toxicity alongside organophosphate toxicity in the differential diagnosis when the atropine challenge test gives a positive result.

Fused human paraoxonase 1 as a prophylactic agent against organophosphate poisoning.

Organophosphates (OPs) are highly neurotoxic compounds and certain OP-compounds are also exploited as a weapon of mass destruction and chemical warfare in terrorist attacks. Available prophylactic and post-exposure treatments are less effective and also have serious side-effects. Thus, there is a dire need to develop effective and safe prophylactic agent(s) against OP-poisoning. Human Paraoxonase 1 (hPON1) can hydrolyze a wide range of OP molecules and can be developed as an effective and safe prophylactic agent. Thus, there is a dire need in the art to develop variant(s) of rhPON1 that not only possess 'good' OP-hydrolyzing activity but also have improved pharmacokinetic properties. In this report, we describe the characterization of the fused hPON1 (FHP) variant that not only exhibit enhanced in vivo pharmacokinetic properties but also delay / prevent the symptoms of OP-poisoning and prevents OP-induced mortality in rats.

Prediction of acute organophosphate poisoning severity using machine learning techniques.

Poisoning with organophosphate compounds is a significant public health risk, especially in developing countries. Considering the importance of early and accurate prediction of organophosphate poisoning prognosis, the aim of this study was to develop a machine learning-based prediction model to predict the severity of organophosphate poisoning. The data of patients with organophosphate poisoning were retrospectively extracted and split into training and test sets in a ratio of 70:30. The feature selection was done by least absolute shrinkage and selection operator method. Selected features were fed into five machine learning techniques, including Histogram Boosting Gradient, eXtreme Gradient Boosting, K-Nearest Neighborhood, Support Vector Machine (SVM) (kernel = linear), and Random Forest. The Scikit-learn library in Python programming language was used to implement the models. Finally, the performance of developed models was measured using ten-fold cross-validation methods and some evaluation criteria with 95 % confidence intervals. A total of 1237 patients were used to train and test the machine learning models. According to the criteria determining severe organophosphate poisoning, 732 patients were assigned to group 1 (patients with mild to moderate poisoning) and 505 patients were assigned to group 2 (patients with severe poisoning). With an AUC value of 0.907 (95 % CI 0.89-0.92), the model developed using XGBoost outperformed other models. Feature importance evaluation found that venous blood gas-pH, white blood cells, and plasma cholinesterase activity were the top three variables that contribute the most to the prediction performance of the prognosis in patients with organophosphate poisoning. XGBoost model yield an accuracy of 90.1 % (95 % CI 0.891-0.918), specificity of 91.4 % (95 % CI 0.90-0.92), a sensitivity of 89.5 % (95 % CI 0.87-0.91), F-measure of 91.2 % (95 % CI 0.90-0.921), and Kappa statistic of 91.2 % (95 % CI 0.90-0.92). The machine learning-based prediction models can accurately predict the severity of organophosphate poisoning. Based on feature selection techniques, the most important predictors of organophosphate poisoning were VBG-pH, white blood cell count, plasma cholinesterase activity, VBG-BE, and age. The best algorithm with the highest predictive performance was the XGBoost classifier.

Novel slow-binding reversible acetylcholinesterase inhibitors based on uracil moieties for possible treatment of myasthenia gravis and protection from organophosphate poisoning.

A series of new compounds in which uracil and 3,6-dimethyluracil moieties are bridged with different spacers were prepared and evaluated in vitro for the acetyl- and butyrylcholinesterase (AChE and BChE) inhibitory activities. These bisuracils are shown to be very effective inhibitors of AChE, inhibiting the enzyme at nano- and lower molar concentrations with extremely high selectivity for AChE vs. BChE. Kinetic analysis showed that the lead compound 2h acts as a slow-binding inhibitor of AChE and possess a long drug-target residence time (τ = 1/koff = 18.6 ± 7.5 min). Moreover, compound 2h ameliorated muscle weakness in myasthenia gravis rat model with a lower effective dose and longer lasting effect than pyridostigmine bromide. Besides, it was shown that compound 2h has an effect of increasing efficiency of antidotal therapy as a pretreatment for poisoning by organophosphates.

The reversed De Ritis ratio for predicting in-hospital mortality among intensive care patients with organophosphate poisoning.

INTRODUCTION: The uncontrolled use of pesticides signifies a substantial health hazard. This study was designed to explore the prognostic role of on-admission hepatic aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the reversed De Ritis ratio (ALT/AST)] in the prediction of in-hospital mortality among patients with acute organophosphate (OP) poisoning. PATIENTS AND METHODS: We conducted a retrospective study based on extracting the required information from the specific medical records for acutely OP-intoxicated patients admitted to the intensive care unit. RESULTS: A total of 49 acutely malathion-intoxicated patients were enrolled in the study. The in-hospital mortality rate was 32.7%. Patients were stratified into survivors and non-survivors. Compared to the survivors, the non-survivors had significantly lower Glasgow coma scale scores, mean arterial blood pressure, significantly higher reversed De Ritis ratio (ALT/AST), and ALT and AST activities. The reversed De Ritis ratio (ALT/AST) and ALT demonstrated good discrimination between the survivors and the non-survivors with an area under the curve (AUC) of 0.708 vs 0.781, respectively, however, AST showed satisfactory discrimination, AUC of 0.694. CONCLUSION: Hepatic aminotransferases are useful in predicting in-hospital mortality in acute OP poisoning. ALT is the most specific biomarker. However, the reversed De Ritis ratio (ALT/AST) is the most sensitive one.

Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning.

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%.