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Toxicology Feb 2021Phosgene (carbonyl dichloride) gas is an indispensable high-production-volume chemical intermediate used worldwide in numerous industrial processes. Published evidence... (Review)
Review
Phosgene (carbonyl dichloride) gas is an indispensable high-production-volume chemical intermediate used worldwide in numerous industrial processes. Published evidence of human exposures due to accidents and warfare (World War I) has been reported; however, these reports often lack specificity because of the uncharacterized exposure intensities of phosgene and/or related irritants. These may include liquid or solid congeners of phosgene, including di- and triphosgene and/or the respiratory tract irritant chlorine which are often collectively reported under the umbrella of phosgene exposure without any appreciation of their differences in causing acute lung injury (ALI). Among these irritants, phosgene gas is somewhat unique because of its poor water solubility. This prevents any appreciable retention of the gas in the upper airways and related trigeminal sensations of irritation. By contrast, in the pulmonary compartment, amphiphilic surfactant might scavenge this lipophilic gas. The interaction of phosgene and the surfactant may affect basic physiological functions controlled by Starling's and Laplace's laws, which can be followed by cardiogenic pulmonary edema. The phenotypic manifestations are dependent on the concentration × exposure duration (C × t); the higher the C × t is, the less time that is required for edema to appear. It is hypothesized that this type of edema is caused by cardiovascular and colloid osmotic imbalances to initial neurogenic events but not because of the injury itself. Thus, hemodynamic etiologies appear to cause imbalances in extravasated fluids and solute accumulation in the pulmonary interstitium, which is not drained away by the lymphatic channels of the lung. The most salient associated findings are hemoconcentration and hypoproteinemia. The involved intertwined pathophysiological processes coordinating pulmonary ventilation and cardiopulmonary perfusion under such conditions are complex. Pulmonary arterial catheter measurements on phosgene-exposed dogs provided evidence of 'cor pulmonale', a form of acute right heart failure produced by a sudden increase in resistance to blood flow in the pulmonary circulation about 20 h postexposure. The objective of this review is to critically analyze evidence from experimental inhalation studies in rats and dogs, and evidence from accidental human exposures to better understand the primary and secondary events causing cardiopulmonary dysfunction and an ensuing life-threatening lung edema. Mechanism-based diagnostic and therapeutic approaches are also considered for this form of cardiogenic edema.
Topics: Acute Lung Injury; Administration, Inhalation; Animals; Chemical Warfare Agents; Humans; Phosgene; Pulmonary Wedge Pressure; Respiration, Artificial
PubMed: 33484734
DOI: 10.1016/j.tox.2021.152682 -
Science Advances Dec 2023Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked...
Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons. How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor that mediates a TOP2-specific DNA damage avoidance pathway. RAD54L2 deficiency conferred unique sensitivity to treatment with TOP2 poisons. RAD54L2 interacted with TOP2A/TOP2B and ZATT/ZNF451 and promoted the turnover of TOP2 from DNA with or without TOP2 poisons. Additionally, inhibition of proteasome activity enhanced the chromatin binding of RAD54L2, which in turn led to the removal of TOP2 from chromatin. In conclusion, we propose that RAD54L2-mediated TOP2 turnover is critically important for the avoidance of potential TOP2-linked DNA damage under physiological conditions and in response to TOP2 poisons.
Topics: Poisons; DNA Topoisomerases, Type II; DNA Damage; DNA Repair; DNA; Chromatin
PubMed: 38055811
DOI: 10.1126/sciadv.adi6681 -
Scientific Reports May 2023The use of metal phosphides, particularly aluminum phosphide, poses a significant threat to human safety and results in high mortality rates. This study aimed to...
The use of metal phosphides, particularly aluminum phosphide, poses a significant threat to human safety and results in high mortality rates. This study aimed to determine mortality patterns and predictive factors for acute zinc and aluminum phosphide poisoning cases that were admitted to Menoufia University Poison and Dependence Control Center from 2017 to 2021. Statistical analysis revealed that poisoning was more common among females (59.7%), aged between 10 and 20 years, and from rural regions. Most cases were students, and most poisonings were the result of suicidal intentions (78.6%). A new hybrid model named Bayesian Optimization-Relevance Vector Machine (BO-RVM) was proposed to forecast fatal poisoning. The model achieved an overall accuracy of 97%, with high positive predictive value (PPV) and negative predictive value (NPV) values of 100% and 96%, respectively. The sensitivity was 89.3%, while the specificity was 100%. The F1 score was 94.3%, indicating a good balance between precision and recall. These results suggest that the model performs well in identifying both positive and negative cases. Additionally, the BO-RVM model has a fast and accurate processing time of 379.9595 s, making it a promising tool for various applications. The study underscores the need for public health policies to restrict the availability and use of phosphides in Egypt and adopt effective treatment methods for phosphide-poisoned patients. Clinical suspicion, positive silver nitrate test for phosphine, and analysis of cholinesterase levels are useful in diagnosing metal phosphide poisoning, which can cause various symptoms.
Topics: Female; Humans; Child; Adolescent; Young Adult; Adult; Aluminum; Bayes Theorem; Phosphines; Aluminum Compounds; Poisons; Heavy Metal Poisoning; Poisoning; Pesticides
PubMed: 37217491
DOI: 10.1038/s41598-023-34489-x -
BMC Public Health Jun 2021Nepal recorded 5754 suicides in 2018-19 - a high number for a relatively small country. Over 24% of these suicides were by poisoning, most by ingestion of highly...
BACKGROUND
Nepal recorded 5754 suicides in 2018-19 - a high number for a relatively small country. Over 24% of these suicides were by poisoning, most by ingestion of highly concentrated agricultural pesticides. Nepal has actively regulated pesticides to reduce their health impacts since 2001. We aimed to analyse Nepal's history of pesticide regulation, pesticides responsible for poisonings, and relate them to national suicide rates.
METHODS
Information on pesticide regulation was collected from the Plant Quarantine and Pesticide Management Centre of the Ministry of Agriculture and Livestock Development. National data on suicides from 1980 to 2019 were obtained from the National Statistical Bureau and Nepal Police. Data on the pesticides responsible for self-poisoning and pesticide suicides over time were obtained from a systematic literature review.
RESULTS
As of June 2020, 171 pesticides were registered for use in Nepal, of which one was extremely hazardous (WHO Class Ia), one other highly hazardous (WHO Class Ib), and 71 moderately hazardous (WHO Class II). Twenty-four pesticides have been banned since 2001, with eight (including five WHO Class I compounds) banned in 2019. Although the suicide rate has increased more than twelve-fold since 1980, particularly for hanging (15-fold increase from 1980 to 2018), fatal pesticide self-poisoning has increased by 13-fold. Methyl-parathion is reported to be the key pesticide responsible for pesticide self-poisoning in Nepal, despite being banned in 2006.
CONCLUSION
The full effect of the recent pesticide policy reform in Nepal remains to be seen. Our analysis shows a continuing increase in suicide numbers, despite bans of the most important pesticide in 2006. This may indicate smuggling across the border and the use of the brand name (Metacid) for pesticides in general making it difficult to identify the responsible pesticide. More information is required from forensic toxicology labs that identify the individual compounds found. The effect of recent bans of common suicide pesticides needs to be monitored over the coming years. Evidence from other Asian countries suggests that HHPs bans will lead to a marked reduction in suicides, as well as fewer cases of occupational poisoning.
Topics: Asia; Eating; Humans; Nepal; Pesticides; Poisoning; Suicide
PubMed: 34120596
DOI: 10.1186/s12889-021-11155-3 -
Annals of the New York Academy of... Nov 2020The use of chemical warfare agents (CWAs) in military conflicts and against civilians is a recurrent problem. Despite ongoing CWA research using in vitro or in vivo... (Review)
Review
The use of chemical warfare agents (CWAs) in military conflicts and against civilians is a recurrent problem. Despite ongoing CWA research using in vitro or in vivo models, progress to elucidate mechanisms of toxicity and to develop effective therapies, decontamination procedures, and general countermeasures is still limited. Novel scientific approaches to address these questions are needed to expand perspectives on existing knowledge and gain new insights. To achieve this, the use of ex vivo techniques like precision-cut tissue slices (PCTSs) can be a valuable approach. Existing studies employing this economical and relatively easy to implement method show model suitability and comparability with the use of in vitro and in vivo models. In this article, we review research on CWAs in PCTSs to illustrate the advantages of the approach and to promote future applications.
Topics: Animals; Chemical Warfare Agents; Humans; Microdissection
PubMed: 32808309
DOI: 10.1111/nyas.14459 -
Shokuhin Eiseigaku Zasshi. Journal of... 2022Histamine poisoning has been reported worldwide. Improvements in refrigeration technology have led to a reduction in this food poisoning; however, it continues to occur.... (Review)
Review
Histamine poisoning has been reported worldwide. Improvements in refrigeration technology have led to a reduction in this food poisoning; however, it continues to occur. Misdiagnosis of fish allergies has compounded this problem and the number of patients subjected to histamine poisoning that are transported to the emergency ward because of anaphylactic shock-like symptoms should not be underestimated. We investigated incidents of histamine food poisoning in Japan from 1998 to 2020, and found that there were a mean 9.7 incidents/year and 195.3 cases/year. Facility-wise occurrence of the incidents per year was the highest in restaurants followed by lunch facilities, and these together accounted for approximately 70% of the incidents. Facility-wise total number of cases was the highest in lunch facilities followed by restaurants, and these together accounted for 80% of the cases. Fish associated with histamine poisoning were mainly tuna, marlin, and mackerel. Based on the current literature review, 23 genera of histamine-producing bacteria were isolated from fish purchased in Japan. The most frequently reported bacteria were Morganella morganii and Photobacterium damselae. Psychrophilic bacteria such as Morganella psychrotolerans and Photobacterium phosphoreum were also isolated. To prevent histamine poisoning, freezing or fast handling of fish and the products during processing and consuming is important because only refrigeration of fish is enough.
Topics: Animals; Bacteria; Fishes; Food Microbiology; Foodborne Diseases; Histamine; Japan
PubMed: 35858795
DOI: 10.3358/shokueishi.63.109 -
Molecules (Basel, Switzerland) Oct 2022Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in... (Review)
Review
Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in the blood of amphibians and toads and can also be extracted from natural products such as plants, herbs, and marines. It is well known that cardiotonic steroids reveal effects against congestive heart failure and atrial fibrillation; therefore, the term "cardiotonic" has been coined. Cardiotonic steroids are divided into two distinct groups: cardenolides (plant-derived) and bufadienolides (mainly of animal origin). Cardenolides have an unsaturated five-membered lactone ring attached to the steroid nucleus at position 17; bufadienolides have a doubly unsaturated six-membered lactone ring. Cancer is a leading cause of mortality in humans all over the world. In 2040, the global cancer load is expected to be 28.4 million cases, which would be a 47% increase from 2020. Moreover, viruses and inflammations also have a very nebative impact on human health and lead to mortality. In the current review, we focus on the chemistry, antiviral and anti-cancer activities of cardiotonic steroids from the naturally derived (toads) venom to combat these chronic devastating health problems. The databases of different research engines (Google Scholar, PubMed, Science Direct, and Sci-Finder) were screened using different combinations of the following terms: "cardiotonic steroids", "anti-inflammatory", "antiviral", "anticancer", "toad venom", "bufadienolides", and "poison chemical composition". Various cardiotonic steroids were isolated from diverse toad species and exhibited superior anti-inflammatory, anticancer, and antiviral activities in in vivo and in vitro models such as marinobufagenin, gammabufotalin, resibufogenin, and bufalin. These steroids are especially difficult to identify. However, several compounds and their bioactivities were identified by using different molecular and biotechnological techniques. Biotechnology is a new tool to fully or partially generate upscaled quantities of natural products, which are otherwise only available at trace amounts in organisms.
Topics: Animals; Antiviral Agents; Biological Products; Bufanolides; Bufonidae; Cardenolides; Cardiac Glycosides; Hormones; Humans; Lactones; Poisons
PubMed: 36235123
DOI: 10.3390/molecules27196586 -
BMC Pediatrics Feb 2024Poisoning among children and adolescents is a public health problem worldwide. To take preventive measures, the pattern of this problem should be determined. This study...
BACKGROUND
Poisoning among children and adolescents is a public health problem worldwide. To take preventive measures, the pattern of this problem should be determined. This study aimed to describe the demographic characteristics of poisoning in children and to investigate the relationship between the types of poisoning and demographic factors in children in Kermanshah province.
METHODS
This cross-sectional, descriptive-analytical study was conducted on 250 children and adolescents under 18 years of age who were referred to Mohammad Kermanshahi Pediatric Hospital in Kermanshah province due to poisoning during 2019-2022. The demographic and epidemiological data of patients were extracted from their medical files and analyzed.
RESULTS
Out of 250 cases of poisoning, 173 (69.2%) cases were unintentional, 96 (55.5%) of whom were boys. Further, 77 (30.8%) cases of poisoning were intentional, of whom 49 (63.6%) were girls. There was a significant difference between gender and intentional and unintentional poisonings (p-value = 0.005). The median age of unintentional poisoning was 3 (IQR = 2.5) and that of intentional poisoning was 14 (IQR = 2). Most cases of poisoning were in cities, 145 (83.8%) of them were unintentional and 66 (85.7%) were intentional. Most cases of intentional and unintentional poisonings occurred in spring 2017 (35.1%) and autumn 2016 (34.6%), respectively. The most common causes of poisoning were narcotics (n = 36, 34.3%) and drugs (n = 35, 33.3%) in the age group 0-3 years and drugs (n = 46, 66.9) in the age group 11-18 years.
CONCLUSIONS
The most common causes of poisoning were narcotics and drugs in children and drugs in adolescents. To prevent poisoning in children, parents are required to increase their knowledge of the safe storage of narcotics and drugs, such as not storing methadone in a water bottle. Targeted evaluation and preventive measures are also needed in adolescent poisoning.
Topics: Child; Male; Female; Humans; Adolescent; Infant, Newborn; Infant; Child, Preschool; Cities; Iran; Cross-Sectional Studies; Methadone; Narcotics; Poisoning
PubMed: 38383350
DOI: 10.1186/s12887-024-04631-3 -
Fa Yi Xue Za Zhi Jun 2022To retrospectively analyze homicide cases of death after injection and provide reference for forensic identification.
OBJECTIVES
To retrospectively analyze homicide cases of death after injection and provide reference for forensic identification.
METHODS
Six homicide cases of death after injection which were investigated by the Criminal Investigation Team of Shanghai Public Security Bureau were collected and analyzed, including case situation, scene investigation, autopsy and other materials.
RESULTS
The 6 cases were premeditated crimes, 5 cases took place in private spaces, and 5 cases involved the victims approached by suspects' decoy. There were no obvious abnormalities at the scene of the 6 cases. In 6 cases, the victim's body surface injury was mild or no, lividity color was abnormal, and the needlestick injury showed different manifestations from conventional medical measures.
CONCLUSIONS
Death after injection is a highly concealed crime and easy to be ignored. For the suspected injection injury found in autopsy, it is necessary to carefully examine, identify and analyze, be alert to the situation of injecting poison (drug) and do a good job in evidence fixation and material extraction.
Topics: Autopsy; China; Homicide; Poisons; Retrospective Studies
PubMed: 36221821
DOI: 10.12116/j.issn.1004-5619.2021.410702 -
Neurobiology of Disease Jan 2020
Topics: Animals; Antidotes; Humans; Medical Countermeasures; Nerve Agents; Neurotoxicity Syndromes
PubMed: 31374245
DOI: 10.1016/j.nbd.2019.104557