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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 -
International Journal of Environmental... Jun 2021Child and youth self-poisoning is a growing public health issue in many regions of the world, including British Columbia (BC), Canada, where 15-19-year-olds have the...
Child and youth self-poisoning is a growing public health issue in many regions of the world, including British Columbia (BC), Canada, where 15-19-year-olds have the highest rates of self-poisoning hospitalizations compared with those of all other ages. The purpose of this study was to identify what substances children and youth commonly used to poison themselves in BC and how socioeconomic status may impact self-poisoning risk. Self-poisoning hospitalization rates among 10-14 and 15-19-year-olds from 1 April 2012 to 31 March 2020 were calculated by substance using ICD-10-CA codes X60-X69 and T36-T65, as well as by socioeconomic status using the Institut National de Santé Publique du Québec's Deprivation Index. Nonopioid analgesics, antipyretics, and antirheumatics were the most common substances involved, with rates of 27.6 and 74.3 per 100,000 population among 10-14 and 15-19-year-olds, respectively, followed by antiepileptic, sedative-hypnotic, antiparkinsonism, and psychotropic drugs, with rates of 20.2 and 68.1 per 100,000 population among 10-14 and 15-19-year-olds, respectively. In terms of socioeconomic status, rates were highest among 10-19-year-olds living in neighbourhoods with the fewest social connections (243.7 per 100,000 population). These findings can inform poisoning prevention strategies and relevant policies, thereby reducing the number of self-poisoning events among children and youth.
Topics: Adolescent; British Columbia; Child; Family; Hospitalization; Humans; International Classification of Diseases; Poisoning; Social Class
PubMed: 34208955
DOI: 10.3390/ijerph18137003 -
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 EMBO Journal Jul 2023Enhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading...
Enhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading to RBM3 expression have been described, the precise molecular mechanism of RBM3 cold induction remains elusive. To identify temperature-dependent modulators of RBM3, we performed a genome-wide CRISPR-Cas9 knockout screen using RBM3-reporter human iPSC-derived neurons. We found that RBM3 mRNA and protein levels are robustly regulated by several splicing factors, with heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) being the strongest positive regulator. Splicing analysis revealed that moderate hypothermia significantly represses the inclusion of a poison exon, which, when retained, targets the mRNA for nonsense-mediated decay. Importantly, we show that HNRNPH1 mediates this cold-dependent exon skipping via its thermosensitive interaction with a G-rich motif within the poison exon. Our study provides novel mechanistic insights into the regulation of RBM3 and provides further targets for neuroprotective therapeutic strategies.
Topics: Humans; Poisons; Cold Shock Proteins and Peptides; Cold Temperature; RNA, Messenger; RNA-Binding Proteins
PubMed: 37248947
DOI: 10.15252/embj.2022113168 -
The American Journal of Emergency... Apr 2022Increasing use of the internet for health information has decreased utilization of traditional telephone-based poison centers in the United States. webPOISONCONTROL®, a...
INTRODUCTION
Increasing use of the internet for health information has decreased utilization of traditional telephone-based poison centers in the United States. webPOISONCONTROL®, a browser-based tool and app was launched to meet the growing demand for online, personalized recommendations for human poison exposures. This study was conducted to characterize webPOISONCONTROL cases and highlight its potential for real-time monitoring of poisoning.
METHODS
Case data for all completed, nonduplicated public cases entered in 2020 were analyzed using a custom Qlik Sense dashboard.
RESULTS
Of the 156,202 cases, 52.9% occurred in children younger than 4 years. Most cases (109,057, 69.8%) were initially triaged to home, 28.4% were advised to call Poison Control, and 1.7% were referred to the ED. Follow-up was available for 33.3% of home-triaged cases; 1.7% of those had a change in triage recommendation. Pharmaceuticals were implicated in 41.5% of cases (nonpharmaceuticals in 58.5%). Ingestion was the most common route (88.4%, 138,012). One-time double dose therapeutic error cases were implicated in 17,901 cases (27.6% of pharmaceutical cases). Cosmetics (13.9%) and cleaning substances (12.9%) were the most frequent substance categories. Melatonin was the most frequently implicated generic substance (4.5% of cases). Most (72.0%) cases had no effect (21.4%), a minor effect (3.9%) or were minimally toxic with unknown outcome (46.7%). There were no deaths, 17 major outcomes (0.01%), and 26.7% of cases had potentially toxic exposures with no outcome determination. In 2020, webPOISONCONTROL handled 7.3% as many human poison exposure cases as were reported to U.S. phone-based poison centers. Online cases are skewed towards younger ages (53% in children younger than 4 years vs 37% of phone-based cases) and towards nonpharmaceuticals (58.5% vs 43.5%). Near real-time data visualizations enabled detection of COVID-19-related increases in exposures to hand sanitizers and cleaners, illustrating the public health surveillance and hazard detection capabilities of webPOISONCONTROL.
CONCLUSION
The webPOISONCONTROL tool provides a safe, quick and fully-automated alternative to those who are unable or unwilling to use the telephone to call a traditional poison center.
Topics: COVID-19; Child; Child, Preschool; Databases, Factual; Humans; Poison Control Centers; Poisoning; Telephone; Triage; United States
PubMed: 35158261
DOI: 10.1016/j.ajem.2022.02.014 -
Toxicon : Official Journal of the... Apr 2021Spontaneous and experimental Stryphnodendron fissuratum poisoning in cattle have been documented in the scientific literature. However, clinical and anatomopathological...
Spontaneous and experimental Stryphnodendron fissuratum poisoning in cattle have been documented in the scientific literature. However, clinical and anatomopathological aspects of such poisoning are not fully understood. Thus, the objective of this study was to describe the clinical, biochemical, gross and microscopic findings of spontaneous Stryphnodendron fissuratum poisoning in cattle as well the experimental poisoning by this plant in sheep. Three outbreaks in cattle from different farms were analyzed. From these farms, S. fissuratum fruit specimens were collected and subsequently administered to six sheep. Some cattle showed clinical signs of poisoning such as blindness, apathy, dysphagia, excessive drooling, weight loss and photodermatitis. In the experimental poisoning condition, one sheep received only the peel of the fruit, one received the seed, and the others received the whole fruit. The whole fruit caused fatal poisoning in one sheep, which showed anorexia, excessive drooling, nystagmus, and paddling. Necropsies and clinical, histopathological, and pathological examination of poisoned cattle and sheep showed that the plant may cause acute renal failure along with extrarenal uremic lesions.
Topics: Animals; Cattle; Cattle Diseases; Disease Outbreaks; Fabaceae; Plant Poisoning; Sheep; Sheep Diseases
PubMed: 33524427
DOI: 10.1016/j.toxicon.2021.01.016 -
Toxins Nov 2019The deliberate release of biological agents with terrorist or criminal intent continues to pose concerns in the current geopolitical situation. Therefore, attention is... (Review)
Review
The deliberate release of biological agents with terrorist or criminal intent continues to pose concerns in the current geopolitical situation. Therefore, attention is still needed to ensure preparedness against the potential use of pathogens as unconventional weapons. Botulinum neurotoxin (BoNT) is one such biological threat, characterized by an extremely low lethal dose, high morbidity and mortality when appropriately disseminated, and the capacity to cause panic and social disruption. This paper addresses the risks of a potential release of the botulinum neurotoxin and summarizes the relevant aspects of the threat.
Topics: Animals; Botulinum Toxins; Chemical Warfare; Chemical Warfare Agents; Crime; Humans; Risk; Terrorism
PubMed: 31757074
DOI: 10.3390/toxins11120681 -
Toxins Oct 2020Animal feeds may contain exogenous compounds that can induce toxicity when ruminants ingest them. These toxins are secondary metabolites originating from various sources... (Review)
Review
Animal feeds may contain exogenous compounds that can induce toxicity when ruminants ingest them. These toxins are secondary metabolites originating from various sources including plants, bacteria, algae and fungi. Animal feed toxins are responsible for various animal poisonings which negatively impact the livestock industry. Poisoning is more frequently reported in newly exposed, naïve ruminants while 'experienced' ruminants are observed to better tolerate toxin-contaminated feed. Ruminants can possess detoxification ability through rumen microorganisms with the rumen microbiome able to adapt to utilise toxic secondary metabolites. The ability of rumen microorganisms to metabolise these toxins has been used as a basis for the development of preventative probiotics to confer resistance against the poisoning to naïve ruminants. In this review, detoxification of various toxins, which include plant toxins, cyanobacteria toxins and plant-associated fungal mycotoxins, by rumen microorganisms is discussed. The review will include clinical studies of the animal poisoning caused by these toxins, the toxin mechanism of action, toxin degradation by rumen microorganisms, reported and hypothesised detoxification mechanisms and identified toxin metabolites with their toxicity compared to their parent toxin. This review highlights the commercial potential of rumen inoculum derived probiotics as viable means of improving ruminant health and production.
Topics: Animal Feed; Animals; Bacteria; Bacterial Toxins; Food Microbiology; Inactivation, Metabolic; Mycotoxins; Plant Poisoning; Plants, Toxic; Probiotics; Rumen; Ruminants
PubMed: 33092236
DOI: 10.3390/toxins12100664 -
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 -
International Journal of Molecular... May 2023V-agents are exceedingly toxic organophosphate nerve agents. The most widely known V-agents are the phosphonylated thiocholines VX and VR. Nonetheless, other... (Review)
Review
V-agents are exceedingly toxic organophosphate nerve agents. The most widely known V-agents are the phosphonylated thiocholines VX and VR. Nonetheless, other V-subclasses have been synthesized. Here, a holistic overview of V-agents is provided, where these compounds have been categorized based on their structures to facilitate their study. A total of seven subclasses of V-agents have been identified, including phospho(n/r)ylated selenocholines and non-sulfur-containing agents, such as VP and EA-1576 (EA: Edgewood Arsenal). Certain V-agents have been designed through the conversion of phosphorylated pesticides to their respective phosphonylated analogs, such as EA-1576 derived from mevinphos. Further, this review provides a description of their production, physical properties, toxicity, and stability during storage. Importantly, V-agents constitute a percutaneous hazard, while their high stability ensures the contamination of the exposed area for weeks. The danger of V-agents was highlighted in the 1968 VX accident in Utah. Until now, VX has been used in limited cases of terrorist attacks and assassinations, but there is an increased concern about potential terrorist production and use. For this reason, studying the chemistry of VX and other less-studied V-agents is important to understand their properties and develop potential countermeasures.
Topics: Chemical Warfare Agents; Organothiophosphorus Compounds; Nerve Agents; Pesticides
PubMed: 37239944
DOI: 10.3390/ijms24108600