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Annales Pharmaceutiques Francaises Sep 2019Organophosphorus compounds (OP) are toxic molecules developed as insecticides and chemical warfare nerve agents (CWNAs). Most OP are neurotoxic and act as nervous system... (Review)
Review
Organophosphorus compounds (OP) are toxic molecules developed as insecticides and chemical warfare nerve agents (CWNAs). Most OP are neurotoxic and act as nervous system disruptors by blocking cholinergic transmission. They are therefore responsible for many poisonings worldwide. OP toxicity may result either from acute or chronic exposure, and their poisoning effect were evaluated using several animal models. These latter were also used for evaluating the efficacy of antidotes. Strategies based on enzymes that can trap (stoichiometric bioscavengers) or degrade (catalytic bioscavengers) OP, were particularly studied since they allow effective decontamination, without toxicity or environmental impact. This review summarizes the results obtained in vivo with enzymes through three levels: prophylaxis, treatment and external decontamination. The efficiency of enzymatic treatments in different animal models is presented and the relevance of these models is also discussed for a better extrapolation to humans.
Topics: Animals; Antidotes; Chemical Warfare Agents; Cholinesterase Reactivators; Enzyme Replacement Therapy; Humans; Insecticides; Organophosphate Poisoning
PubMed: 31253354
DOI: 10.1016/j.pharma.2019.06.002 -
Arhiv Za Higijenu Rada I Toksikologiju Dec 2020Phosphylation of the pivotal enzyme acetylcholinesterase (AChE) by nerve agents (NAs) leads to irreversible inhibition of the enzyme and accumulation of neurotransmitter... (Review)
Review
Phosphylation of the pivotal enzyme acetylcholinesterase (AChE) by nerve agents (NAs) leads to irreversible inhibition of the enzyme and accumulation of neurotransmitter acetylcholine, which induces cholinergic crisis, that is, overstimulation of muscarinic and nicotinic membrane receptors in the central and peripheral nervous system. In severe cases, subsequent desensitisation of the receptors results in hypoxia, vasodepression, and respiratory arrest, followed by death. Prompt action is therefore critical to improve the chances of victim's survival and recovery. Standard therapy of NA poisoning generally involves administration of anticholinergic atropine and an oxime reactivator of phosphylated AChE. Anticholinesterase compounds or NA bioscavengers can also be applied to preserve native AChE from inhibition. With this review of 70 years of research we aim to present current and potential approaches to counteracting NA poisoning.
Topics: Acetylcholinesterase; Chemical Warfare; Chemical Warfare Agents; Cholinesterase Inhibitors; Cholinesterase Reactivators; Humans; Nerve Agents; Organophosphate Poisoning; Oximes
PubMed: 33410774
DOI: 10.2478/aiht-2020-71-3459 -
Current Biology : CB Nov 2015Stynoski et al. introduce the dendrobatids, a charismatic group of frogs known for their colourful and often poisonous skin.
Stynoski et al. introduce the dendrobatids, a charismatic group of frogs known for their colourful and often poisonous skin.
Topics: Animals; Anura; Female; Male; Poisons; Skin; Skin Pigmentation; Toxins, Biological
PubMed: 26528739
DOI: 10.1016/j.cub.2015.06.044 -
Theranostics 2021Poisons always have fascinated humankind. Initially considered as deleterious or hazardous substances, the modern era has witnessed the controlled utilization of... (Review)
Review
Poisons always have fascinated humankind. Initially considered as deleterious or hazardous substances, the modern era has witnessed the controlled utilization of dangerous poisons in medicine and cosmetics. Simultaneously, antidotes have become crucial as reversal agents to counteract the effects of a poison, and they are also used today to positively cancel the benefits of a poison after use. Currently, the majority of poisons are composed of small molecules. This review focuses on recent developments to reverse or prevent toxic effects of poisons by encapsulation in host molecules. Cyclodextrins, cucurbiturils, acyclic cucurbituril derivatives, calixarenes, and pillararenes, have been reported to largely impact the effects of toxic compounds, thus extending the current paradigm of small molecule antidotes by adding a new family of macrocyclic compounds to the current arsenal of antidotes. Along this line of research, endogenous "harmful" species are also sequestered by one or more of these supramolecular host molecules, expanding the potential of supramolecular antidotes to diverse therapeutic areas.
Topics: Animals; Antidotes; Humans; Macrocyclic Compounds; Poisons; Small Molecule Libraries
PubMed: 33391548
DOI: 10.7150/thno.53459 -
The Veterinary Clinics of North... Nov 2020The liver is one of the most commonly affected organs by ingested toxicants. This article familiarizes veterinarians with clinical signs, serum biochemistry changes,... (Review)
Review
The liver is one of the most commonly affected organs by ingested toxicants. This article familiarizes veterinarians with clinical signs, serum biochemistry changes, necropsy findings, and field information found in livestock poisonings with hepatotoxic plants. The focus is on the most common plant-derived hepatotoxins important to livestock in North America. Pyrrolizidine alkaloids are covered in greater detail than the other toxins, because they are likely the most important plant-derived toxins worldwide in livestock, wildlife, and even human exposure. Additionally, many of the principles discussed regarding clinical diagnosis of pyrrolizidine alkaloid intoxication can be applied to the other poisonous plants listed.
Topics: Animals; Cattle; Cattle Diseases; Liver Diseases; Livestock; North America; Plant Poisoning; Plants, Toxic; Pyrrolizidine Alkaloids
PubMed: 33032701
DOI: 10.1016/j.cvfa.2020.08.003 -
BMC Public Health Jan 2022Self-harm and suicide are important causes of morbidity and mortality in Sri Lanka, but our understanding of these behaviours is limited. Qualitative studies have...
BACKGROUND
Self-harm and suicide are important causes of morbidity and mortality in Sri Lanka, but our understanding of these behaviours is limited. Qualitative studies have implicated familial and societal expectations around sex and relationships. We conducted an explorative analysis using case-control data to investigate the association between sex education and self-poisoning in Sri Lanka.
METHODS
Cases (N=298) were self-poisoning inpatients on a toxicology ward, Teaching Hospital Peradeniya. Controls (N=500) were sex and age frequency matched to cases and were outpatients/visitors to the same hospital. Participants were asked whether they had received sex education, and to rate the quality and usefulness of any sex education received. Logistic regression models adjusted for age, sex, and religion quantified the association between receipt, quality and usefulness of sex education and self-poisoning. We tested whether the associations differed by sex.
RESULTS
Roughly 1-in-3 cases and 1-in-5 controls reported having not received sex education. Individuals who did not receive sex education were nearly twice as likely to have self-poisoned than those who did (OR 1.68 (95% CI 1.11-2.55)). Those who reported the sex education they received as not useful were more likely to have self-poisoned compared to those who reported it useful (OR 1.95 (95% CI 1.04-3.65)). We found no evidence of an association between self-poisoning and the self-rated quality of sex education, or that associations differed by participant sex.
CONCLUSION
As sex education is potentially modifiable at the population-level, further research should aim to explore this association in more depth, using qualitative methods and validated measurement tools.
Topics: Humans; Poisoning; Poisons; Self-Injurious Behavior; Sex Education; Sri Lanka; Suicide
PubMed: 34991547
DOI: 10.1186/s12889-021-12374-4 -
Annals of the New York Academy of... Nov 2020Although 193 states have committed to the Chemical Weapons Convention and 98% of the declared chemical weapons stockpiles have been destroyed so far, nerve agent... (Review)
Review
Although 193 states have committed to the Chemical Weapons Convention and 98% of the declared chemical weapons stockpiles have been destroyed so far, nerve agent poisoning remains a lingering threat. The recent dissemination of sarin in Syria, the assassination of Kim Jong-Nam in Malaysia, and the assault on Sergei Skripal in the United Kingdom underline the need for effective treatment. The current therapeutic options of a muscarinic receptor antagonist, an oxime, and an anticonvulsant have been unchanged for decades. Therefore, new therapeutic strategies, for example, bioscavengers and receptor-active substances, are promising concepts that have to be examined for their benefits and limitations. In order to facilitate rapid diagnosis in challenging clinical situations, point-of-care diagnostics and detection are of importance. Therapeutic guidance concerning the duration and success of the current oxime therapy via determination of the cholinesterase status can contribute to an optimal use of resources. In summary, the challenges of current and future therapies for nerve agent poisoning and key diagnostic devices will be discussed.
Topics: Antidotes; Cholinesterase Reactivators; Humans; Nerve Agents; Organophosphate Poisoning; Oximes; Sarin; United Kingdom
PubMed: 32198755
DOI: 10.1111/nyas.14336 -
Journal of Medical Toxicology :... Jun 2017Despite the existence of a number of severity-of-illness classifications for other areas of medicine, toxicology research lacks a well-accepted method for assessing the... (Review)
Review
INTRODUCTION
Despite the existence of a number of severity-of-illness classifications for other areas of medicine, toxicology research lacks a well-accepted method for assessing the severity of poisoning. The Poisoning Severity Score (PSS) was developed in the 1990s in Europe as a scoring system for poisonings reported to a poison center in order to describe a patient's most severe symptomatology. We reviewed the literature to describe how the PSS is utilized and describe its limitations.
DISCUSSION
We searched the medical literature in all languages using PUBMED, EMBASE, and SCOPUS from inception through August 2013 using predefined search terms. Out of 204 eligible publications, 40 met our criteria for inclusion in this review. There has been a paucity of published studies from North America that used the PSS. In some cases, the PSS was misapplied or modified from standard scoring, making a bottom line appraisal of the validity or reliability of the original version of the instrument challenging. The PSS has several subjective criteria, is time consuming to score, and is likely to be of little use with some types of poisonings, limiting its clinical utility.
CONCLUSION
The PSS was developed as a tool to document encounters with poisoned patients. However, it is used infrequently and, when applied, has been misused or modified from its original form. In its current form, it has limited clinical utility and likely cannot be broadly applied to many exposures due to their unique clinical circumstances. With better global collaboration among medical toxicologists, it is possible that a modified score could be developed for use clinically or as a research instrument.
Topics: Decision Support Techniques; Humans; Poisoning; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index
PubMed: 28283941
DOI: 10.1007/s13181-017-0609-5 -
Wilderness & Environmental Medicine Mar 2016The American Association of Poison Control Centers has continued to report approximately 50,000 telephone calls or 8% of incoming calls annually related to plant... (Review)
Review
The American Association of Poison Control Centers has continued to report approximately 50,000 telephone calls or 8% of incoming calls annually related to plant exposures, mostly in children. Although the frequency of plant ingestions in children is related to the presence of popular species in households, adolescents may experiment with hallucinogenic plants; and trekkers and foragers may misidentify poisonous plants as edible. Since plant exposures have continued at a constant rate, the objectives of this review were (1) to review the epidemiology of plant poisonings; and (2) to propose a rapid toxidromic classification system for highly toxic plant ingestions for field use by first responders in comparison to current classification systems. Internet search engines were queried to identify and select peer-reviewed articles on plant poisonings using the key words in order to classify plant poisonings into four specific toxidromes: cardiotoxic, neurotoxic, cytotoxic, and gastrointestinal-hepatotoxic. A simple toxidromic classification system of plant poisonings may permit rapid diagnoses of highly toxic versus less toxic and nontoxic plant ingestions both in households and outdoors; direct earlier management of potentially serious poisonings; and reduce costly inpatient evaluations for inconsequential plant ingestions. The current textbook classification schemes for plant poisonings were complex in comparison to the rapid classification system; and were based on chemical nomenclatures and pharmacological effects, and not on clearly presenting toxidromes. Validation of the rapid toxidromic classification system as compared to existing chemical classification systems for plant poisonings will require future adoption and implementation of the toxidromic system by its intended users.
Topics: Emergency Medicine; Humans; Plant Poisoning; Plants, Toxic
PubMed: 26948561
DOI: 10.1016/j.wem.2015.11.006 -
Archives of Toxicology Jul 2020Organophosphorus (OP) pesticides and nerve agents still pose a threat to the population. Treatment of OP poisoning is an ongoing challenge and burden for medical... (Review)
Review
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.
Topics: Animals; Antidotes; Atropine; Cholinesterase Reactivators; Humans; Nerve Agents; Organophosphate Poisoning; Organophosphonates; Oximes; Pesticides; Treatment Outcome
PubMed: 32506210
DOI: 10.1007/s00204-020-02797-0