Organophosphate Poisoning Research Articles

Acute NETosis from organophosphate poisoning

Acute <scp>NETosis</scp> from organophosphate poisoning

Neuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.

Organophosphates (OPs) and nerve agents are potent neurotoxic compounds that cause seizures, status epilepticus (SE), brain injury, or death. There are persistent long-term neurologic and neurodegenerative effects that manifest months to years after the initial exposure. Current antidotes are ineffective in preventing these long-term neurobehavioral and neuropathological changes. Additionally, there are few effective neuroprotectants for mitigating the long-term effects of acute OP intoxication. We have pioneered neurosteroids as novel anticonvulsants and neuroprotectants for OP intoxication and seizures. In this study, we evaluated the efficacy of two novel synthetic, water-soluble neurosteroids, valaxanolone (VX) and lysaxanolone (LX), in combating the long-term behavioral and neuropathological impairments caused by acute OP intoxication and SE. Animals were exposed to the OP nerve agent surrogate diisopropylfluorophosphate (DFP) and were treated with VX or LX in addition to midazolam at 40 minutes postexposure. The extent of neurodegeneration, along with various behavioral and memory deficits, were assessed at 3 months postexposure. VX significantly reduced deficits of aggressive behavior, anxiety, memory, and depressive-like traits in control (DFP-exposed, midazolam-treated) animals; VX also significantly prevented the DFP-induced chronic loss of NeuN(+) principal neurons and PV(+) inhibitory neurons in the hippocampus and other regions. Additionally, VX-treated animals exhibited a reduced inflammatory response with decreased GFAP(+) astrogliosis and IBA1(+) microgliosis in the hippocampus, amygdala, and other regions. Similarly, LX showed significant improvement in behavioral and memory deficits, and reduced neurodegeneration and cellular neuroinflammation. Together, these results demonstrate the neuroprotectant effects of the novel synthetic neurosteroids in mitigating the long-term neurologic dysfunction and neurodegeneration associated with OP exposure. SIGNIFICANCE STATEMENT: Survivors of nerve agents and organophosphate (OP) exposures suffer from long-term neurological deficits. Currently, there is no specific drug therapy for mitigating the impact of OP exposure. However, novel synthetic neurosteroids that activate tonic inhibition provide a viable option for treating OP intoxication. The data from this study indicates the neuroprotective effects of synthetic, water-soluble neurosteroids for attenuation of long-term neurological deficits after OP intoxication. These findings establish valaxanolone and lysaxanolone as potent and efficacious neuroprotectants suitable for injectable dosing.

Acute oral poisoning due to pretilachlor herbicide – a rare case report from Nepal

Introduction: Acute oral intoxication of pretilachlor, a synthetic chloroacetanilide herbicide, can present similar clinical manifestations of organophosphorus toxicity in humans. Case presentation: A 15-year-old male was admitted after suicidal ingestion of pretilachlor poison, with decreased consciousness and blood-mixed vomiting. Discussion: Pretilachlor is a colorless and odorless liquid that can cause neurotoxicity and carcinogenicity due to its prolonged exposure. The effects of acute oral exposure are mild and may differ from chronic exposure. Individuals exposed to chloroacetanilides may not show symptoms or experience vomiting and neurological issues. Clinical manifestations such as vomiting, excessive lacrimation, bowel and bladder incontinence, bradycardia, and hypotension can be observed in both organophosphate poisoning and pretilachlor poisoning, making accurate diagnosis challenging, particularly in resource-limited settings like ours. There is no specific antidote for pretilachlor poisoning. Treatment focuses on symptomatic care and monitoring the patient’s hemodynamics as per standard protocol. Conclusion: This case underscores the need for prompt stabilization, vigilant monitoring, and supportive care to ensure timely recovery in pretilachlor poisoning cases despite similarities with organophosphate poisoning. It emphasizes the importance of educating and raising awareness among physicians about potential mimickers like organophosphates.

A Prospective Observational Study of Acid Base Disorders in Organophosphorous Poisoning in a Tertiary Care Centre

A Prospective Observational Study of Acid Base Disorders in Organophosphorous Poisoning in a Tertiary Care Centre

Protective Activity of Novel Hydrophilic Synthetic Neurosteroids on Organophosphate Status Epilepticus-induced Chronic Epileptic Seizures, Non-Convulsive Discharges, High-Frequency Oscillations, and Electrographic Ictal Biomarkers.

Nerve agents and organophosphates (OP) are neurotoxic chemicals that induce acute seizures, status epilepticus (SE), and mortality. Long-term neurologic and neurodegenerative effects manifest months to years after OP exposure. Current benzodiazepine anticonvulsants are ineffective in preventing such long-term neurobehavioral and neuropathological changes. New and effective anticonvulsants are needed for OP intoxication, especially for mitigating the long-term sequelae after acute exposure. We developed neurosteroids as novel anticonvulsants and neuroprotectants in OP exposure models. In this study, we evaluated the long-term efficacy of novel synthetic neurosteroids in preventing the development of chronic epilepsy and hyperexcitable ictal events in a rat OP model of SE. Rats were exposed to the OP nerve agent surrogate diisopropylfluorophosphate (DFP), and the experimental groups were treated with the synthetic neurosteroid valaxanolone (VX) or lysaxanolone (LX) 40 minutes post-exposure in conjunction with midazolam. Video-electroencephalography was monitored for two months to assess spontaneous recurrent seizures (SRS), epileptiform discharges, interictal spikes, and high-frequency oscillations (HFOs). Within 60 days of DFP exposure, rats developed chronic epilepsy characterized by frequent SRS, epileptiform discharges, and HFOs. LX treatment was associated with a dose-dependent reduction of epilepsy occurrence and overall seizure burden with a significant decrease in SRS and epileptiform discharges. It also significantly reduced the occurrence of epileptic biomarkers of HFOs and interictal spikes, indicating potential disease-modifying activity. Similarly, the neurosteroid analog VX also significantly attenuated SRS, discharges, HFOs, and ictal events. These results demonstrate the long-term protective effects of synthetic neurosteroids in the OP-exposed post-SE model, indicating their disease-modifying potential to prevent epilepsy and ictal abnormalities. SIGNIFICANCE STATEMENT: The effects of nerve agents and organophosphate (OP) exposure are persistent, and survivors suffer from a number of devastating, chronic neurological dysfunctions. Currently, there is no specific therapy for preventing this disastrous impact of OP exposure. We propose synthetic neurosteroids that activate tonic inhibition provide viable options for preventing the long-term neurological effects of OP intoxication. The results from this study reveal the disease-modifying potential of two novel synthetic neurosteroids in preventing epileptogenesis and chronic epileptic seizures after OP-induced SE.

A Case Study on Organophosphate Poisoning in Dehradun

Organophosphate compounds are used as commercial insecticides and applied as aerosols or dust. Consuming these compounds intentionally or unintentionally lead to dangerous conditions even to fatality. The most common obstacle in treating organophosphorus poisoning is the availability of sufficient medical care, equipment to provide proper emergency care observed in rural areas where there is a lot of gaps between intensive care and acute care. Atropine use is as an antidote in organophosphorus poisoning. The dose of atropine mainly depends on the organophosphorus toxic doses. Atropine is a competitive antagonist of acetylcholine at the muscarinic postsynaptic membrane. Atropine blocks all the muscarinic effects in the body. The authors present a case of suicidal OP poisoning with an overview of management of the acute intoxication. The early recognition of symptoms and prompt treatment helps in reducing the morbidity and mortality.

Approach to non-compressive myeloneuropathy through a rendezvous of 11 cases from an Indian backdrop

IntroductionMyeloneuropathy is a diagnosis ascribed to disorders that concomitantly affect the spinal cord and peripheral nerves. Recognizing this syndrome may sometimes be arduous, even for the most consummate clinicians, because symptomatology can mimic either spinal cord or peripheral nerve disease. Besides, examination findings suggest a predominantly myelopathic or neuropathic picture. This article reports a rendezvous of rare cases of clinically diagnosed myeloneuropathy with different etiological backgrounds and therapeutic responses. MethodsEleven cases of non-compressive myeloneuropathy were admitted to the Department of General Medicine of Burdwan Medical College and Hospital, Burdwan, West Bengal, India, between May 2018 and May 2022. ResultsWe report the cases of 11 patients (6 men and 5 women) who presented with myeloneuropathy of different etiologies (vitamin B12, copper, and vitamin E deficiencies, organophosphate poisoning, chronic alcohol abuse, illicit substances abuse, anti-thyroid peroxidase/anti-thyroglobulin antibody-related neurologic disorder responsive to steroids, Sjögren syndrome, chikungunya infection, paraneoplastic, and hereditary). ConclusionMeticulous historical analysis, careful clinical examination, and apposite utilization and interpretation of biochemical, electrophysiological, and neuroimaging findings are sine-qua-non for an accurate and consistent approach to evaluating a suspected case of myeloneuropathy, facilitating early treatment and recovery. Differential identification of these disorders needs an in-depth perception of the mode of onset of symptoms, the course of progression of the disease, the pattern of myelopathic/neuropathic findings, and recognition of other neurological or systemic manifestations. For untroubled understanding, etiologies of myeloneuropathies should be subdivided into a few broad categories, e.g., metabolic (nutritional), toxic (toxin-induced), infectious, inflammatory (immune-mediated), paraneoplastic, and hereditary disorders.

Suspected intermediate syndrome in a dog after organophosphate poisoning.

To discuss the clinical presentation and successful treatment of a suspected case of intermediate syndrome due to organophosphate (OP) poisoning in a dog. 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 24hours postingestion. One dog developed an onset of neurological signs consistent with intermediate syndrome approximately 24hours postingestion. This patient's clinical signs resolved with the use of pralidoxime chloride. 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.

Literature Review: Impact of Organophosphate Pesticide Exposure on Cholinesterase Enzyme Activity and Associated Risk Factors for Poisoning, 2017-2020

Introduction: Organophosphate pesticides, which are used to control pests of crops, affect the nervous system by inhibiting the activity of cholinesterase enzymes in the body. This can be achieved by inhaling, eating, or applying it to the skin. This study research aims to determine the level of pesticide exposure that can inhibit the activity of the Cholinesterase enzyme in the blood. This study employed a systematic literature review with library sources used through Google Scholar and Science Direct, resulting in 16 research articles discussing cholinesterase enzyme activity due to exposure to organophosphates discussed in 2017-2020. Discussion: The results of a previous study found that exposure to organophosphates significantly reduced cholinesterase enzyme activity by 50-80%. Testing for cholinesterase as a biomarker of exposure to Organophospate (OP) through acetylcholinesterase activity in red blood cells (AChE). This study explored the relationship between gender, age, knowledge of farmers, personal protective equipment, farmers’ smoking behavior, and duration of spraying. Conclusion: Poisoning alters the activity of cholinesterase enzymes in the blood of farmers, resulting in acute and chronic health problems. Several factors have been found to correlate with organophosphate poisoning, including age, level of knowledge among farmers, use of personal protective equipment, smoking behavior, and duration of spraying activities.

Evaluation of the performance of an handheld device for measuring cholinesterase activity, in order to use in cases of organophosphate poisoning

Cholinesterase activity monitoring during the organophosphorus pesticides poisoning is still a challenge in the remote areas. The objective of this study was to evaluate the performance of the Test-mate Model 400 EQM® for the determination of cholinesterase. This is a cross-sectional analytical study conducted with two different levels of quality control sera (QCs) and 40 sera of different cholinesterase concentrations from patients samples. The coefficient of variation obtained for repeatability was compared to the supplier's values. Spearman's coefficient and kappa coefficient (ĸ) were used to examine correlation and assess agreement between measurements obtained with the handheld device and the INDIKO analyzer, used as a reference test. For repeatability of EQM Test-mate ChE®, coefficients of variation was 5.5% and 6% for the normal and pathological control sera respectively, that is lower than 7.5% as recommended by the supplier. A Spearman correlation coefficient of r=0.7451 (p&lt;0.0001) was obtained and a good agreement between the measurements ( ĸ=0.7253 (95%CI: 0.655- 0.841)). This handheld device is repeatable and showed a good correlation and agreement with the INDIKO® analyzer. It would therefore be suitable for determining cholinesterase activity in remote areas in case of organophosphate poisoning.

Study of clinical profile and outcome of poisoning in children admitted to a tertiary care hospital

Background: A poison is any substance that causes harm to a living being. Children are curious and explore their world with all their senses. Every year thousands of children are admitted to emergency department with poisoning. Poisoning pattern changes according to age group, the nature, dose of the poison, type of exposure. This study is aimed at understanding the incidence, aetiology, manner of poisoning and outcome among children less than 18 years of age admitted to Paediatric emergency department. Methods: This is a Prospective observational study conducted in Paediatrics, MMC and RI, Mysore (Cheluvaba Hospital) between January 2019 to June 2019. After taking ethical committee clearance. 142 children with poisoning admitted to emergency department were included in this study. The age and sex of the patient, poisoning agent, manner of poisoning, duration of hospital stay and outcome of all the patients were recorded and analysed. Results: Out of 142, 78 (54.9%) cases are males, 64 (45.1%) cases are females. 91 (64.1%) cases are &lt;5 years of age, 17 (12%) cases are between 5-10 year, 34 (23.9%) cases are above 10 years. Among all, 38 (26%) cases of drugs consumption. 65 (45.8%) cases of kerosene consumption. 21 (14.8%) cases of insecticides and pesticides poison. Unknown compound 18 (12.7%) cases. 4 (2.8%) cases died- aluminium phosphide poisoning 3 (75%) and Organophosphorous poison 1 (25%). Duration of hospital stay varied from 1 day to more than 15 days. Conclusions: Accidental poisoning is common in children below 5 years of age. Suicidal poisoning incidence is increasing among teenagers either due to exam stress or peer pressure. Accidental poisoning can be reduced by simple measures like parental education, replacing the poisoning agent with one of lower toxicity, legislation regarding the child resistant packaging of necessary poisons.

Study of Organophosphorus Poisoning at a Tertiary Care Teaching Hospital

Introduction: Organophosphate (OP) insecticides inhibit both cholinesterase and pseudo-cholinesterase activities. The inhibition of acetylcholinesterase causes accumulation of acetylcholine at synapses, and overstimulation of neurotransmission occurs as a result of this accumulation. The mortality rate of OP poisoning is high. Early diagnosis and appropriate treatment is often life saving. Treatment of OP poisoning consists of intravenous atropine and oximes. The clinical course of OP poisoning may be quite severe and may need intensive care management. Methods: A retrospective study was performed on the patients with OP poisoning. Fifty patients were included. Diagnosis was performed from the history taken either from the patient or from the patient's relatives about the agent involved in the exposure. Diagnosis could was confirmed with serum and red blood cell anticholinesterase levels. Intravenous atropine and pralidoxime was administered as soon as possible. Other measures for the treatment were gastric lavage and administration of activated charcoal via nasogastric tube, and cleansing the patient's body with soap and water. The patients were intubated and mechanically ventilated if the patients had respiratory failure, a depressed level of consciousness, which causes an inability to protect the airway, and hemodynamic instability. Mechanical ventilation was performed as synchronized intermittent mandatory ventilation + pressure support mode, either as volume or pressure control. Positive end expiratory pressure was titrated to keep SaO2 above 94% with 40% FIO2. Weaning was performed using either T-tube trials or pressure support weaning. The chi-square test was used for statistical analysis. Data are presented as mean ± standard deviation. Results: There were 26 female and 24 male patients. Thirty-five were suicide attempts and 15 were accidental exposure. The gastrointestinal route was the main route in 44 patients. The most frequent signs were meiosis, change in mental status, hypersalivation and fasciculations. Ten patients (20.0%) required mechanical ventilation. Complications were observed in 35 patients. These complications were respiratory failure (14 patients), aspiration pneumonia (10 patients), urinary system infection (6 patients), convulsion (4 patients) and septic shock (1 patient). The duration of the intensive care stay was 5.2 ± 3.0 days. Discussion: Ingestion of OP compounds for suicidal purposes is a major problem, especially in developing countries. Thirty-five of our patients used the OP insecticide for suicide. The average respiratory rate of these patients increased from 22 to 38 breaths/min, which is an important sign of respiratory distress. The nurse to patient ratio was increased after these events. Early recognition of respiratory failure resulting in intubation and mechanical ventilation is a life-saving intervention for patients with OP poisoning. Respiratory failure is the most troublesome complication, which was observed in 35 patients. Patients with OP poisoning may have respiratory failure for many reasons, including aspiration of the gastric content, excessive secretions, pneumonia and septicemia complicating acute respiratory distress syndrome. Conclusions: OP insecticide poisoning is a serious condition that needs rapid diagnosis and treatment. Since respiratory failure is the major reason for mortality, careful monitoring, appropriate management and early recognition of this complication may decrease the mortality rate among these patients.

Long-Term Neuropsychiatric Developmental Defects after Neonatal Organophosphate Exposure: Mitigation by Synthetic Neurosteroids.

Children are much more susceptible to the neurotoxic effects of organophosphate (OP) pesticides and nerve agents than adults. OP poisoning in children leads to acute seizures and neuropsychiatric sequela, including the development of long-term disabilities and cognitive impairments. Despite these risks, there are few chronic rodent models that use pediatric OP exposure for studying neurodevelopmental consequences and interventions. Here, we investigated the protective effect of the neurosteroid ganaxolone (GX) on the long-term developmental impact of neonatal exposure to the OP compound, diisopropyl-fluorophosphate (DFP). Pediatric postnatal day-28 rats were acutely exposed to DFP, and at 3 and 10 months after exposure, they were evaluated using a series of cognitive and behavioral tests with or without the postexposure treatment of GX. Analysis of the neuropathology was performed after 10 months. DFP-exposed animals displayed significant long-term deficits in mood, anxiety, depression, and aggressive traits. In spatial and nonspatial cognitive tests, they displayed striking impairments in learning and memory. Analysis of brain sections showed significant loss of neuronal nuclei antigen(+) principal neurons, parvalbumin(+) inhibitory interneurons, and neurogenesis, along with increased astrogliosis, microglial neuroinflammation, and mossy fiber sprouting. These detrimental neuropathological changes are consistent with behavioral dysfunctions. In the neurosteroid GX-treated cohort, behavioral and cognitive deficits were significantly reduced and were associated with strong protection against long-term neuroinflammation and neurodegeneration. In conclusion, this pediatric model replicates the salient features of children exposed to OPs, and the protective outcomes from neurosteroid intervention support the viability of developing this strategy for mitigating the long-term effects of acute OP exposure in children. SIGNIFICANCE STATEMENT: An estimated 3 million organophosphate exposures occur annually worldwide, with children comprising over 30% of all victims. Our understanding of the neurodevelopmental consequences in children exposed to organophosphates is limited. Here, we investigated the long-term impact of neonatal exposure to diisopropyl-fluorophosphate in pediatric rats. Neurosteroid treatment protected against major deficits in behavior and memory and was well correlated with neuropathological changes. Overall, this pediatric model is helpful to screen novel therapies to mitigate long-term developmental deficits of organophosphate exposure.

Evidence Implicating Blood-Brain Barrier Impairment in the Pathogenesis of Acquired Epilepsy following Acute Organophosphate Intoxication.

Organophosphate (OP) poisoning can trigger cholinergic crisis, a life-threatening toxidrome that includes seizures and status epilepticus. These acute toxic responses are associated with persistent neuroinflammation and spontaneous recurrent seizures (SRS), also known as acquired epilepsy. Blood-brain barrier (BBB) impairment has recently been proposed as a pathogenic mechanism linking acute OP intoxication to chronic adverse neurologic outcomes. In this review, we briefly describe the cellular and molecular components of the BBB, review evidence of altered BBB integrity following acute OP intoxication, and discuss potential mechanisms by which acute OP intoxication may promote BBB dysfunction. We highlight the complex interplay between neuroinflammation and BBB dysfunction that suggests a positive feedforward interaction. Lastly, we examine research from diverse models and disease states that suggest mechanisms by which loss of BBB integrity may contribute to epileptogenic processes. Collectively, the literature identifies BBB impairment as a convergent mechanism of neurologic disease and justifies further mechanistic research into how acute OP intoxication causes BBB impairment and its role in the pathogenesis of SRS and potentially other long-term neurologic sequelae. Such research is critical for evaluating BBB stabilization as a neuroprotective strategy for mitigating OP-induced epilepsy and possibly seizure disorders of other etiologies. SIGNIFICANCE STATEMENT: Clinical and preclinical studies support a link between blood-brain barrier (BBB) dysfunction and epileptogenesis; however, a causal relationship has been difficult to prove. Mechanistic studies to delineate relationships between BBB dysfunction and epilepsy may provide novel insights into BBB stabilization as a neuroprotective strategy for mitigating epilepsy resulting from acute organophosphate (OP) intoxication and non-OP causes and potentially other adverse neurological conditions associated with acute OP intoxication, such as cognitive impairment.

Organophospate-Induced Pathology: Mechanisms of Development, Principles of Therapy and Features of Experimental Studies

Organophosphates (OP) are one of the most common neurotoxic xenobiotics. In acute OP poisoning, as a result of suppression of synaptic acetylcholinesterase (AChE) activity, a cholinergic syndrome develops, which can transform into status epilepticus. Within a few days after acute poisoning, the so-called an intermediate syndrome can develop, which is associated with prolonged inhibition of AChE, desensitization of nicotinic receptors, and functional degradation of synapses and muscle fibers. In 10–20 days after a single acute or repeated subacute poisoning, OP-induced delayed polyneuropathy (OPIDN) can develop – a neurodegenerative disease, the signs of which are ataxia, loss of function of the distal sensory and motor axons of peripheral nerves. The occurrence of a neuropsychiatric disorder (NPD) caused by chronic exposure to relatively low-toxicity organophosphorus compounds is usually not associated with acute poisoning; symptoms include cognitive impairment, chronic fatigue, and extrapyramidal symptoms. The list of possible diseases or pathological conditions (syndromes) that develop as a result of acute, subacute or chronic effects of OP on the human body has expanded in recent years due a number of known neurodegenerative diseases (Alzheimer’s, Parkinson’s, multiple sclerosis, etc.). The aging of the body in general and the aging of the brain in particular are considered in the review from the point of view of the consequences of OP poisoning, which can serve as a nonspecific trigger of aging and related neurodegenerative diseases. Gulf syndrome is not a consequence of OP intoxication, but is also of interest and is considered in the context of OP-induced pathology, since its etiology and pathogenesis are associated with the exposure to cholinesterase inhibitors. The review presents data indicating the important role of the vascular endothelium in the development of OP-induced pathology; The first suggestions were made by clinicians in the late 1980s, and the first experimental data were obtained in the early 2000s. The principles of therapy for acute poisoning are outlined, taking into account experimental data from recent years. Some methods for studying OP in experiments in vitro, ex vivo and in vivo with laboratory animals, including the use of carboxylesterase inhibitors, are presented. The most important part of in vivo investigations has been and remains the search for new biomarkers to assess the effectiveness of adjuvant and regenerative therapies.

Time- and region-dependent blood-brain barrier impairment in a rat model of organophosphate-induced status epilepticus

Acute organophosphate (OP) intoxication can trigger seizures that progress to status epilepticus (SE), and survivors often develop chronic morbidities, including spontaneous recurrent seizures (SRS). The pathogenic mechanisms underlying OP-induced SRS are unknown, but increased BBB permeability is hypothesized to be involved. Previous studies reported BBB leakage following OP-induced SE, but key information regarding time and regional distribution of BBB impairment during the epileptogenic period is missing. To address this data gap, we characterized the spatiotemporal progression of BBB impairment during the first week post-exposure in a rat model of diisopropylfluorophosphate-induced SE, using MRI and albumin immunohistochemistry. Increased BBB permeability, which was detected at 6 h and persisted up to 7 d post-exposure, was most severe and persistent in the piriform cortex and amygdala, moderate but persistent in the thalamus, and less severe and transient in the hippocampus and somatosensory cortex. The extent of BBB leakage was positively correlated with behavioral seizure severity, with the strongest association identified in the piriform cortex and amygdala. These findings provide evidence of the duration, magnitude and spatial breakdown of the BBB during the epileptogenic period following OP-induced SE and support BBB regulation as a viable therapeutic target for preventing SRS following acute OP intoxication.

A Case of Acute Pancreatitis in Organophosphate Poisoning

Organophosphate (OP) poisoning is one of the most harmful and easily accessible pesticides for suicide poisoning. It is linked to high mortality and morbidity. Cholinergic syndrome, intermediate syndrome, and syndrome of delayed polyneuropathy are the three primary syndromes that characterize OP poisoning. Organophosphates are strong toxins that are frequently used as pesticides in agriculture. Patients who have consumed organophosphorus may exhibit subclinical symptoms of acute pancreatitis. Correct biochemical analysis and clinical correlation assist in diagnosis. In the study, we described a 24-year-old female who suffered necrotizing pancreatitis after OP poisoning. Keywords: Organophosphate Poisoning, Pesticide, Pancreatitis.

Sex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.

Sex differences are common in human epilepsy. Although men are more susceptible to seizure than women, the mechanisms underlying sex-specific vulnerabilities to seizure are unclear. The organophosphate (OP) diisopropylfluorophosphate (DFP) is known to cause neurotoxicity and status epilepticus (SE), a serious neurologic condition that causes prolonged seizures and brain damage. Current therapies for OP poisoning and SE do not consider neuronal variations between male and female brains. Therefore, we investigated sex-dependent differences in electrographic seizure activity and neuronal injury using the DFP model of refractory SE in rats. Electroencephalogram recordings were used to monitor DFP-induced SE, and the extent of brain injury was determined using fluoro-jade-B staining to detect cellular necrosis. After DFP exposure, we observed striking sex-dependent differences in SE and seizure activity patterns as well as protective responses to midazolam treatment. Following acute DFP exposure, male animals displayed more severe SE with intense epileptiform spiking and greater mortality than females. In contrast, we observed significantly more injured cells and cellular necrosis in the hippocampus and other brain regions in females than in males. We also observed extensive neuronal injury in the somatosensory cortex of males. The anticonvulsant effect of midazolam against SE was limited in this model and found to be similar in males and females. However, unlike males, females exhibited substantially more protection against neuronal damage after midazolam treatment. Overall, these results demonstrate significant sex-dependent differences in DFP-induced refractory SE and neuronal damage patterns, suggesting that it may be possible to develop sex-specific neuroprotective strategies for OP intoxication and refractory SE. SIGNIFICANCE STATEMENT: Sex-dependent differences in neurotoxicity and status epilepticus (SE) are key biological variables after organophosphate (OP) exposure. Here, we investigated sex-dependent differences in SE and brain injury after acute diisopropylfluorophosphate exposure. Male rats had more severe SE and less survival than females, while females had more neuronal damage. Females had more neuroprotection to midazolam than males, while both sexes had similar but partial anticonvulsant effects. These findings suggest that a sex-specific therapeutic approach may prevent neurological complications of OP-induced SE.

A comparative study of atropine and atropine plus pralidoxime in the management of organo-phosphorous poisoning

Background: Poisoning with organophosphorus compounds (OP) is a common problem throughout the world particularly in developing countries. Standard treatment involves resuscitation, administration of the anti-muscarinic agent atropine, an acetylcholinesterase reactivator (pralidoxime) and assisted ventilation if necessary. In this study we compared the efficacy of add-on pralidoxime therapy over therapy with atropine alone in OP poisoning. Methods: The study included 103 patients, out of 103 OP poisoning cases, 54 patients received both atropine and PAM (group A) and 49 received only atropine (group B). Main outcome parameters of the study were total hospital stay and mortality. The data was compared using ‘t’ test while mortality was compared using Fisher’s exact test. Data was tabulated, analysed, reviewed and evaluated. Results: There was no difference in duration of hospital stay between the two group. The mean hospital stay in group A was 3.71±1.92 days and in group B was 3.14±2.01 days (p value &gt;0.05). No difference in mortality was seen between the two group. Out of 54 in group A, 8 died and in group B out of 49, 7 died (p value &gt;0.05). Importantly cost burden is very high in the pralidoxime added group. Conclusions: There is no significant difference in use of atropine alone or atropine-pralidoxime combination in terms of morbidity and mortality in OP poisoning rather the later incurs more economic burden which may not be practicable in poor countries like India. However, a larger multicentric prospective study needs to be conducted, to be able to draw a definitive conclusion.

Detection the severity of organophosphate intoxication using sensitive serum biomarkers S100B and amyloid β (Aβ) in Egyptian subjects

Organophosphate (OP) is a compound considered the main leading cause of morbidity and mortality from poisoning worldwide. Serum pseudocholinesterase was evaluated as a diagnostic indicator; it cannot be used to monitor therapy or severity of the intoxication. The rationale of the current study was to evaluate sensitivity, specificity, and cut-off values of serum S100B and amyloid β for neurological affection severity. This study was carried out on sixty OP-impaired patients; in addition, 20 normal controls were included. Serum liver and kidney function tests, malondialdehyde, pseudocholinesterase, and the levels of S100B and amyloid β (Aβ) were determined. Data showed that Pearson’s analysis indicated that the serum level of S100B was positively correlated with Aβ. On the contrary, the activity of pseudocholinesterase was negatively correlated with both of S100B and Aβ. Serum ALT, AST, creatinine, urea, acetylcholine, and MDA levels were elevated while pseudocholinesterase activity was reduced in moderate and severe OP intoxication versus control. A drastic elevation (p<0.001) in the levels of S100B and Aβ was performed in the patient group suffering from OP intoxication versus the normal group. The diagnostic statistical validation of targeted parameters in distinguishing between moderate OP intoxication and control clarifies that S100B displayed the best AUC (0.997) followed by Aβ (AUC=0.992), while the diagnostic veracity of S100B and Aβ in setting apart severe OP-intoxicated and normal subjects stated the symmetric efficacy of potential markers. It was concluded that the significant changes in the levels of S100B and Aβ were directly proportional to the degree of severity of OP intoxication.