- Organophosphate-pyrethroid combined poisoning may be associated with prolonged cholinergic symptoms compared to either poison alone. [Journal Article]
- IJIndian J Anaesth 2018; 62(11):903-905
- One-year mortality among hospital survivors of cholinesterase inhibitor poisoning based on Taiwan National Health Insurance Research Database from 2003 to 2012. [Journal Article]
- BPBMC Pharmacol Toxicol 2018 Nov 13; 19(1):72
- CONCLUSIONS: The one-year mortality rate of survivors after CI poisoning was 6.7%. Meanwhile, age, pneumonia, and mechanical ventilation may be predictive factors for the one-year mortality among the survivors after CI poisoning. Diabetes mellitus was not a risk factor for hospital mortality in patients with CI poisoning.
- Effect of cholinergic crisis on the potency of different emergency anaesthesia protocols in soman-poisoned rats. [Journal Article]
- CTClin Toxicol (Phila) 2018 Oct 11; :1-7
- CONCLUSIONS: The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals.Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.
- Neurotoxic effects of organophosphorus pesticides and possible association with neurodegenerative diseases in man: A review. [Journal Article]
- TToxicology 2018 Dec 01; 410:125-131
- In this article the neurotoxic disorders appearing in patients exposed to organophosphorus pesticides and known mechanisms involved are reviewed. Organophosphorus compounds cause four main neurotoxic...
In this article the neurotoxic disorders appearing in patients exposed to organophosphorus pesticides and known mechanisms involved are reviewed. Organophosphorus compounds cause four main neurotoxic effects in humans: the cholinergic syndrome, the intermediate syndrome, organophosphate-induced delayed polyneuropathy and chronic organophosphate-induced neuropsychiatric disorder. Compared to the cholinergic syndrome, that causes millions of cases of poisoning with fatality of more than 15% each year, other disorders involve much smaller number of patients. Possible link of exposure to organophosphorus pesticides with neurodegenerative diseases, dementia, attention deficit hyperactivity disorder and Parkinson's disease in man is also approached. This article is focused on neurotoxic disorders appearing after acute and chronic exposure to organophosphates with emphasis on molecular mechanisms, clinical presentation, pathogenesis, and possibilities for prevention/medical treatment.
- Prediction of organophosphorus insecticide-induced intermediate syndrome with stimulated concentric needle single fibre electromyography. [Journal Article]
- PlosPLoS One 2018; 13(9):e0203596
- CONCLUSIONS: Prolonged jitter recorded with SfEMG <24 hours of ingestion of an OP strongly correlates with subsequent occurrence of IMS. The time course of electrophysiological recovery of the NMJ was similar to the time course of respiratory recovery in IMS patients.
- Addition of ketamine to standard-of-care countermeasures for acute organophosphate poisoning improves neurobiological outcomes. [Journal Article]
- NNeurotoxicology 2018; 69:37-46
- Rats poisoned with sarin enter into ahyper-cholinergic crisis characterized by excessive salivation, respiratory distress, tremors, seizures, and death. Through the use of rescue medications and an a...
Rats poisoned with sarin enter into ahyper-cholinergic crisis characterized by excessive salivation, respiratory distress, tremors, seizures, and death. Through the use of rescue medications and an anticonvulsant, death can be avoided in many animals, with the long-term consequences of poisoning partly ameliorated, especially when countermeasures are made available immediately after exposure. However, when anticonvulsant measures are delayed by as little as 30 min, clinical, neurological, cognitive, and psychiatric abnormalities may persist long after the initial exposure. This study sought to determine if the addition of the NMDA receptor antagonist Ketamine to human standard-of-care countermeasures consisting of two rescue medications (2-PAM and atropine) and an anti-convulsant (Midazolam), would afford protection against persistent neurobiological compromise. Rats were exposed to sarin (105 μg/kg via subcutaneous injection), and treated 1 min later with 2-PAM and Atropine Methyl Nitrate (IM) to minimize mortality. One of four anti-convulsant protocols was then initiated at 50 min postsarin:Midazolam alone (MDZ, a single injection (IM) at 0.66 mg/kg); Ketamine alone (KET, a series of five injections (IM) of Ketamine at 7.5 mg/kg, 90 min apart); Midazolam + low dose Ketamine (MDZ + lowKET, a single injection of Midazolam (IM) at 0.66 mg/kg, plus five sequential doses of ketamine (IM) at 2.5 mg/kg, starting at the time of Midazolam dosing and then 90 min apart); Midazolam + high dose Ketamine (MDZ + highKET, a single injection of Midazolam (IM) at 0.66 mg/kg, plus five sequential injections of 7.5 mg/kg Ketamine (IM), starting at the time of Midazolam dosing and then 90 min apart). Animals were preassigned to groups culled at post-exposure Days 1, 7 or 30, for histopathology. For all surviving animals, EEG activity was monitored through skull electrodes for 24-h beginning immediately after sarin exposure. Surviving animals also underwent 24-h EEG monitoring on Days 6, 13, and/or 29, post-sarin. Memory assessment using the Morris Water Maze was performed on Days 1, 4, 7, 14 and 30. Following sarin exposure, 85% of surviving animals demonstrated status epilepticus within 20 min. Each of the anti-convulsant protocols was sufficient to stop convulsions within 1 h of anti-convulsant administration, but all of the animals still showed signs of electrographic status for an additional 2-12 h, without substantial differentiation between treatment groups. However, for post-sarin hours 13-24, the MDZ + highKET group showed significantly less severe EEG abnormalities than the MDZ and KET groups (Mood's Median Test, p < 0.005). At one month post-exposure, 90% of animals that had received Midazolam alone still showed evidence of some epileptiform activity. In contrast, 90% of animals that had received Midazolam + high dose Ketamine combination therapy had EEG profiles that were within normal limits. This difference in EEG outcomes was highly significant (Mood's Median Test, p < 0.001). Likewise, on the water maze, the majority of animals that had received Midazolam combined with either high or low dose Ketamine therapy returned to near baseline levels of mnemonic performance within 2 weeks, whereas the majority of the animals that had received midazolam alone or ketamine alone demonstrated persistent and significant memory impairments even at one month postexposure (Mood's Median Test, p < 0.005). With respect to neuronal necrosis, animals in the MDZ + highKET group showed significantly less overall damage than animals in other treatment groups (Mood's Median Test, p < 0.001). Of special note were findings in the hippocampus, where only 12% of animals in the MDZ + highKET group showed evidence of necrosis on H&E staining, whereas 100% of animals in the KET group, 70% of animals in the MDZ group, and 40% of animals in the MDZ + lowKET group showed evidence of hippocampal necrosis. Overall, the data demonstrate that Ketamine augmentation of an atropine, 2PAM, and Midazolam standard-ofcare for sarin exposure provides clinically-relevant additional protection against the negative neurobiological consequences of sarin, even when initiation of the anti-convulsant countermeasures is delayed by 50 min.
- Blood-brain barrier breakdown, memory impairment and neurotoxicity caused in mice submitted to orally treatment with thymol. [Journal Article]
- ETEnviron Toxicol Pharmacol 2018; 62:114-119
- Several evidences have related the biochemical and pharmacological properties of thymol, but the possible neurotoxic effects of this compound remain unknown and not evaluated. Thus, the purpose of th...
Several evidences have related the biochemical and pharmacological properties of thymol, but the possible neurotoxic effects of this compound remain unknown and not evaluated. Thus, the purpose of this study was to evaluate whether intake of thymol in different doses (10, 20 and 40 mg/kg) induce neurotoxicity and behavioral alterations using mice as experimental model, as well as the involvement of blood-brain barrier (BBB) and brain neurotransmitters in these alterations. Thymol (20 and 40 mg/kg) significantly decrease latency time to inhibitory avoidance task when compared to control group, indicating a memory loss after 30 days of oral treatment. Also, thymol (20 and 40 mg/kg) induced a significant increase on BBB permeability to Evan's blue dye when compared to control group, which is an indicative of BBB breakdown. Moreover, a significant increase of brain acetylcholinesterase (AChE) was observed in mice treated with 40 mg/kg of thymol, while the activity of sodium-potassium pump (Na+, K+-ATPase) was inhibited in mice treated with 20 and 40 mg/kg thymol when compared to control group. Finally, mice that received 20 and 40 mg/kg thymol showed a significant increase on cerebral reactive oxygen species (ROS) levels and cerebral xanthine oxidase (XO) activity compared to control group. Based on these evidences, the rupture of BBB can be considered an important pathway linked in thymol-induced memory loss. Also, the augmentation of brain ROS levels elicited by increase on XO activity may be a via involved in the damage to BBB, and an oxidative pathway that impairs the activity of brain neurotransmitters, as AChE and Na+, K+-ATPase. In summary, the dose of 10 mg/kg thymol can be safe and without neurotoxic effects in a period of 30 days of intake.
- Prolonged paralysis in a child with organophosphate pesticide poisoning. [Case Reports]
- SAS Afr Med J 2018 05 25; 108(6):468-470
- A 17-month-old boy presented to a local community health centre in Cape Town, South Africa, with severe organophosphate pesticide poisoning (OPP), necessitating the use of intravenous atropine to con...
A 17-month-old boy presented to a local community health centre in Cape Town, South Africa, with severe organophosphate pesticide poisoning (OPP), necessitating the use of intravenous atropine to control cholinergic symptoms, as well as emergency intubation for ongoing respiratory distress. He required prolonged ventilatory support in the intensive care unit at his referral hospital and had subsequent delayed neurological recovery, spending 8 days in hospital.We present this case to emphasise the importance of adequate atropinisation in the management of severe OPP and to highlight the dangers of inappropriate use of suxamethonium for intubation in patients with OPP.
- Novichok agents: a historical, current, and toxicological perspective. [Journal Article]
- TCToxicol Commun 2018; 2(1):45-48
- The Novichok, or "newcomer" class of nerve agents are lesser characterized, weaponized organophosphate agents. The use of known Novichok agents in warfare is banned under the Chemical Weapons Convent...
The Novichok, or "newcomer" class of nerve agents are lesser characterized, weaponized organophosphate agents. The use of known Novichok agents in warfare is banned under the Chemical Weapons Convention of 1997. Novichok agents are considered more potent than VX gas and can be applied in unitary and binary forms. Like other nerve agents, Novichok agents irreversibly bind acetylcholinesterase and produce a cholinergic toxidrome. Uniquely, these agents are thought to also target neurons in the peripheral nervous system. Delayed treatment or massive exposure may therefore cause a debilitating neuropathy. The recent 2018 assassination attempt of Russian dissident Sergei Skripal and his daughter Yulia in the United Kingdom highlights the importance of recognizing the potential lethal effects of these nerve agents. Treatment of Novichok agent poisoning is similar to management of other nerve agents. Given increasing worldwide incidents attributed to chemical weapons such as Novichok agents, clinicians should know how to rapidly recognize symptoms of acute poisoning and administer life-saving antidotal therapy, when indicated.
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- Acute cholinergic syndrome in a patient with Alzheimer's disease taking the prescribed dose of galantamine. [Journal Article]
- PPsychogeriatrics 2018; 18(5):434-435