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Rachna, Singh MP, Goswami S, Singh UK. Pesticide pollution: toxicity, sources and advanced remediation approaches. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2024; 31:64385-64418. [PMID: 39541023 DOI: 10.1007/s11356-024-35502-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024]
Abstract
The Food and Agricultural Organization of the United Nations (FAO) estimates that food production must rise by 70% to meet the demands of an additional 2.3 billion people by 2050. This forecast underscores the persistent reliance on pesticides, making it essential to assess their toxicity and develop effective remediation strategies. Given the widespread utilisation of pesticides, it requires an urgent need to evaluate their toxicity and explore feasible remediation approaches for their removal. Hence, this review provides an overview of the latest information on the presence, distribution, sources, fate, and trends of pesticides in global environmental matrices, emphasizing the ecological and health risks posed by pesticide pollution. Currently, the dominant remediation techniques encompass physical, chemical, and biological methods, yet studies focusing on advanced remediation techniques remain limited. This review critically evaluates both newer and traditional approaches to pesticide removal, offering a descriptive and analytical comparison of various methods. The selection of the appropriate treatment method depends largely on the nature of the pesticide and the effectiveness of the chosen technique. In many cases, technologies such as membrane bioreactors and the fenton process could be integrated with biological technologies to enhance performance and overcome limitations. The study concludes that a hybrid approach combining various remediation strategies offers the most effective and sustainable solution for pesticide removal. Finally, the review underscores the need for further scientific investigation into the most viable technologies while discussing the challenges and prospects of developing safe, reliable, cost-effective, and eco-friendly methods for removing pesticides from the environment.
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Affiliation(s)
- Rachna
- Department of Environmental Science, Central University of South Bihar, Gaya, Bihar, India
| | - Mohan Prasad Singh
- Centre of Biotechnology, University of Allahabad, Prayagraj, 211002, Uttar Pradesh, India
| | - Shreerup Goswami
- Department of Geology, Utkal University, Vani Vihar, Bhubaneswar, 751004, Odisha, India
| | - Umesh Kumar Singh
- Department of Environmental Science, Central University of South Bihar, Gaya, Bihar, India.
- Centre of Environmental Studies, University of Allahabad, Prayagraj, 211002, Uttar Pradesh, India.
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Choi S, Kim GW, Lim H. A narrative review of contemporary lethal pesticides: unveiling the ongoing threat of pesticide poisoning. Clin Exp Emerg Med 2024; 11:335-348. [PMID: 38286498 DOI: 10.15441/ceem.23.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 01/02/2024] [Indexed: 01/31/2024] Open
Abstract
Following the 2011 ban on paraquat sales, Korea has witnessed a significant reduction in the mortality rate associated with acute pesticide poisoning. Traditionally, paraquat and diquat, alongside several highly toxic organophosphates, carbamates, and organochlorine insecticides, have been recognized as culprits in causing fatalities among patients with acute pesticide poisoning. However, despite global efforts to curtail the use of these highly toxic pesticides, certain pesticides still exhibit a level of lethality surpassing their established clinical toxicity profiles. Understanding the clinical progression of these pesticides is paramount for physicians and toxicologists, as it holds the potential to enhance patient prognoses in cases of acute poisoning. This review aims to address the persistence of such highly lethal pesticides, which continue to pose a grave threat to victims of acute poisoning.
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Affiliation(s)
- Sangchun Choi
- Department of Emergency Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Gi Woon Kim
- Department of Emergency Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Hoon Lim
- Department of Emergency Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
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Meier C, Burns K, Manolikos C, Fatovich D, Bell DA. Hyperammonaemia: review of the pathophysiology, aetiology and investigation. Pathology 2024; 56:763-772. [PMID: 39127541 DOI: 10.1016/j.pathol.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 06/14/2024] [Accepted: 06/18/2024] [Indexed: 08/12/2024]
Abstract
Acute hyperammonaemia is a medical emergency as it can progress to cerebral oedema, seizures, coma and death. Hepatic encephalopathy secondary to cirrhotic disease or portosystemic shunting are relatively well-known causes, but non-cirrhotic aetiologies of acute hyperammonaemia are less well-known, especially in the emergency department. However, an elevated ammonia is not required to make the diagnosis of hepatic encephalopathy. Although measurement of plasma ammonia is recommended for patients with acute, unexplained, altered mental status, as early identification allows early effective management which may prevent irreversible brain damage, there is currently reduced awareness among physicians of the non-cirrhotic aetiologies of acute hyperammonaemia. Furthermore, measurement of ammonia in patients with cirrhosis has been shown to have low sensitivity and specificity, and not to have altered management in the majority of cases; thus, measurement of ammonia is currently not recommended in guidelines for management of hepatic encephalopathy. We sought to describe the pathophysiology of hyperammonaemia and review the non-cirrhotic causes. This was achieved by review of MEDLINE, PubMed and Web of Science databases to include published English literature within the last 20 years. We also present a framework for investigating the acute non-cirrhotic causes of hyperammonaemia to assist both chemical pathologists and clinicians managing these often challenging cases.
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Affiliation(s)
- Ciselle Meier
- The University of Western Australia, Perth, WA, Australia
| | - Kharis Burns
- The University of Western Australia, Perth, WA, Australia; Inborn Errors of Metabolism Service, Department of Endocrinology, Royal Perth Hospital, Perth, WA, Australia
| | - Catherine Manolikos
- Inborn Errors of Metabolism Service, Department of Endocrinology, Royal Perth Hospital, Perth, WA, Australia
| | - Daniel Fatovich
- Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia; Emergency Department, Royal Perth Hospital, The University of Western Australia, Perth, WA, Australia
| | - Damon A Bell
- The University of Western Australia, Perth, WA, Australia; Inborn Errors of Metabolism Service, Department of Endocrinology, Royal Perth Hospital, Perth, WA, Australia; PathWest Laboratory Medicine, Department of Biochemistry, Fiona Stanley Hospital Network, Perth, WA, Australia.
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Zhao S, Xiao L, Sun Y, Jiang Z, Yang L, Zhang J, Ye Y. Forensic toxicological studies of acute glufosinate poisoning: A case series. J Forensic Leg Med 2024; 106:102732. [PMID: 39089135 DOI: 10.1016/j.jflm.2024.102732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 07/15/2024] [Accepted: 07/23/2024] [Indexed: 08/03/2024]
Abstract
Glufosinate is a widely and increasingly used non-selective, broad-spectrum herbicide. Although cases of glufosinate poisoning are frequently reported, they are rarely documented in forensic case reports, particularly in fatal instances. The present study examined six cases of glufosinate poisoning, including a fatal case involving a 25-year-old female found deceased by the roadside, with an empty 1000 mL bottle labeled "glufosinate" by her side. Biological specimens such as plasma or cardiac blood, gastric contents, and liver tissues were collected for quantitative analysis of glufosinate levels using LC-MS/MS. In five cases of acute glufosinate poisoning, glufosinate plasma concentrations ranged from 0.62 to 3.92 μg/mL. In the fatal case, the concentrations of glufosinate in cardiac blood, gastric contents, and liver tissues were 8.41 μg/mL, 31.25 μg/mL, and 66.1 μg/g, respectively. The pathological autopsy concluded that the cause of death was acute cardio-respiratory failure due to glufosinate poisoning, characterized by multi-organ congestion without specific pathological findings. The toxicological data provided in this study aim to serve as a critical reference for future clinical treatment and forensic validation of glufosinate poisoning-related deaths.
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Affiliation(s)
- Shuang Zhao
- Department of Forensic Toxicological Analysis, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Li Xiao
- Department of Forensic Toxicological Analysis, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yimin Sun
- Department of Forensic Toxicological Analysis, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Zihan Jiang
- Department of Forensic Toxicological Analysis, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Lin Yang
- Department of Forensic Toxicological Analysis, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jing Zhang
- West China School of Public Health and West China Fourth Hospital, Chengdu, 610016, Sichuan, China.
| | - Yi Ye
- Department of Forensic Toxicological Analysis, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
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Qiang S, Mohamed F, Raubenheimer J, Buckley NA, Roberts MS, Mackenzie L. Clinical toxicology of acute glyphosate self-poisoning: impact of plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amine surfactants on the toxicity. Clin Toxicol (Phila) 2024; 62:483-496. [PMID: 39073455 DOI: 10.1080/15563650.2024.2375584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 06/20/2024] [Accepted: 06/27/2024] [Indexed: 07/30/2024]
Abstract
INTRODUCTION Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amines can predict acute kidney injury and case fatality in glyphosate poisoning. METHODS We enrolled 151 patients with acute glyphosate poisoning between 2010 and 2013. Plasma concentrations of glyphosate, its metabolite, aminomethylphosphonic acid, and polyethoxylated tallow amines were determined in 2020 using liquid chromatography-tandem mass spectrometry. Associations between exposure and poisoning severity were assessed. RESULTS Plasma concentrations of glyphosate and aminomethylphosphonic acid demonstrated good and moderate performances in predicting acute kidney injury (≥2), with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.69-0.97) and 0.76 (95% CI 0.59-0.94), respectively. Polyethoxylated tallow amines were detected in one-fifth of symptomatic patients, including one of four fatalities and those with unsaturated tallow moieties being good indicators of acute kidney injury (area under the receiver operating characteristic curve ≥0.7). As the number of repeating ethoxylate units in tallow moieties decreased, the odds of acute kidney injury increased. Glyphosate and aminomethylphosphonic acid concentrations were excellent predictors of case fatality (area under the receiver operating characteristic curve >0.9). DISCUSSION The 2.7% case fatality rate with 49% acute, albeit mild, acute kidney injury following glyphosate poisoning is consistent with previously published data. A population approach using model-based metrics might better explore the relationship of exposure to severity of poisoning. CONCLUSIONS Plasma concentrations of glyphosate and its metabolite predicted the severity of clinical toxicity in glyphosate poisoning. The co-formulated polyethoxylated tallow amine surfactants were even more strongly predictive of acute kidney injury but were only detected in a minority of patients.
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Affiliation(s)
- Shuping Qiang
- University of South Australia Clinical and Health Sciences, University of South Australia, Adelaide, Australia
- Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia
| | - Fahim Mohamed
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
- Translational Australian Clinical Toxicology (TACT) Research Group, Discipline of Biomedical Informatics & Digital Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
- The Edith Collins Centre (Translational Research in Alcohol Drugs and Toxicology), Sydney Local Health District, Sydney, Australia
| | - Jacques Raubenheimer
- Translational Australian Clinical Toxicology (TACT) Research Group, Discipline of Biomedical Informatics & Digital Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Nicholas A Buckley
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
- Translational Australian Clinical Toxicology (TACT) Research Group, Discipline of Biomedical Informatics & Digital Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Michael S Roberts
- University of South Australia Clinical and Health Sciences, University of South Australia, Adelaide, Australia
- Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia
- Therapeutics Research Centre, The University of Queensland Frazer Institute, The University of Queensland, Brisbane, Australia
| | - Lorraine Mackenzie
- University of South Australia Clinical and Health Sciences, University of South Australia, Adelaide, Australia
- Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia
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Liu M, Fan F, Zhang J, Fang S, Bai Y, Li Y, Zou Y, An Y, Dai X. Simultaneous determination of diquat, paraquat, glufosinate, and glyphosate in plasma by liquid chromatography/tandem mass spectrometry: from method development to clinical application. Anal Bioanal Chem 2024:10.1007/s00216-024-05257-1. [PMID: 38514583 DOI: 10.1007/s00216-024-05257-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/11/2024] [Accepted: 03/13/2024] [Indexed: 03/23/2024]
Abstract
Diquat (DQ), paraquat (PQ), glufosinate (GLU), and glyphosate (GLYP) are commonly used herbicides that have been confirmed to be toxic to humans. Rapid and accurate measurements of these toxicants in clinical practice are beneficial for the correct diagnosis and timely treatment of herbicide-poisoned patients. The present study aimed to establish an efficient, convenient, and reliable method to achieve the simultaneous quantification of DQ, PQ, GLU, and GLYP in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) without using derivatization or ion-pairing reagents. DQ, PQ, GLU, and GLYP were extracted by the rapid protein precipitation and liquid-liquid extraction method and then separated and detected by LC-MS/MS. Subsequently, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, extraction recovery, matrix effect, dilution integrity, and stability were evaluated to validate the method based on the FDA criteria. Finally, the validated method was applied to real plasma samples collected from 166 Chinese patients with herbicide poisoning. The results showed satisfactory linearity with low LOD (1 ng/mL for DQ and PQ, 5 ng/mL for GLU, and 10 ng/mL for GLYP, respectively) and low LOQ (5 ng/mL for DQ and PQ, 25 ng/mL for GLU and GLYP, respectively). In addition, the precision, accuracy, extraction recovery, and stability of the method were acceptable. The matrix effect was not observed in the analyzed samples. Moreover, the developed method was successfully applied to determine the target compounds in real plasma samples. These data provided reliable evidence for the application of this LC-MS/MS method for clinical poisoning detection.
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Affiliation(s)
- Maozhu Liu
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Fei Fan
- West China School of Basic Medical Science & Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jing Zhang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Shiyong Fang
- School of Forensic Medicine, Wannan Medical College, Wuhu, 241002, Anhui, China
| | - Yangjuan Bai
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yamei Li
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yuangao Zou
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yunfei An
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xinhua Dai
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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Zhang Y, Dang Y, Pei F, Yuan Y, Yuan J, Gu Z, Wang J. Sub-acute toxicity of the herbicide glufosinate-ammonium exposure in adult red swamp crayfish (Procambarus clarkii). ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 337:122605. [PMID: 37742863 DOI: 10.1016/j.envpol.2023.122605] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 09/20/2023] [Accepted: 09/21/2023] [Indexed: 09/26/2023]
Abstract
Glufosinateammonium (GLA) is one of the most widely used agricultural herbicides. It is frequently detected in surface waters near farmland and may pose a risk to non-target aquatic species. This study aimed to explore the toxicity of subacute GLA exposure in crayfish. Adult red swamp crayfish were exposed to GLA (0, 1, 10, and 100 mg/L) for 21 days. Bioaccumulation, oxidative stress, nonspecific immunity, and the expression of genes encoding xenobiotic detoxification-related enzymes were examined. The results showed GLA accumulation and hepatopancreatic histopathological changes (dilation of hepatic tubules and vacuolation of hepatocytes) in the exposed crayfish. GLA exposure induced ROS production, inhibited glutathione expression, and catalase activity in the crayfish hepatopancreas, as well as inhibited immunoenzyme expression (acid phosphatase, alkaline phosphatase, and lysozyme) in the hemolymph. In addition, the total hemocyte number decreased, and the proportion of hemocyte subsets changed significantly. Superoxide dismutase first increased and then decreased with increasing GLA dosage. GLA promoted the expression of biotransformation enzymes (cypb5, gst) in the hepatopancreas. Our results suggest that subacute GLA exposure caused structural damage to the hepatopancreatic tissue and decreased antioxidant capacity and non-specific immunity in crayfish. These findings provide insight into the toxicity of herbicides on non-target organisms.
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Affiliation(s)
- Yang Zhang
- College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China
| | - Yao Dang
- State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou, 510655, China
| | - Fucheng Pei
- College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China
| | - Yongchao Yuan
- College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China
| | - Junfa Yuan
- College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China; Hubei Engineering Technology Research Center for Aquatic Animal Disease Control and Prevention, Wuhan, 430070, China
| | - Zemao Gu
- College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China; Hubei Engineering Technology Research Center for Aquatic Animal Disease Control and Prevention, Wuhan, 430070, China
| | - Jianghua Wang
- College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
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The trend of ammonia levels in patients with glufosinate ammonium poisoning with respect to neurotoxicity. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:525-531. [PMID: 36399183 DOI: 10.1007/s00210-022-02327-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 11/04/2022] [Indexed: 11/19/2022]
Abstract
Since glufosinate irreversibly inhibits glutamine synthetase, leading to intracellular accumulation of ammonia, hyperammonemia is considered one of the main mechanisms of glufosinate ammonium toxicity in humans. However, whether hyperammonemia causes neurotoxicity has not yet been studied. Therefore, the purpose of this study was to determine whether the serum ammonia level is elevated before the development of neurotoxicity. In this retrospective observational study, we analyzed data from consecutive patients diagnosed with acute glufosinate ammonium poisoning. The primary outcome was the development of neurotoxicity following the poisoning. Patients who developed neurotoxicity were characterized by higher initial ammonia levels compared to patients without neurotoxicity (121.0 µg/dL [87.0; 141.0] vs 83.0 µg/dL [65.0; 119.0], p < 0.01). However, there was no increase in ammonia levels over time in both the asymptomatic and neurotoxicity groups when serial serum ammonia levels were examined from emergency department admission to hospital discharge. In addition, there was no statistically significant difference between the peak ammonia levels in the asymptomatic group and the peak ammonia levels before symptom onset in the neurotoxicity group (135.0 µg/dL [109.0; 158.0] vs 144.0 µg/dL [120.0; 189.0], p = 0.15). Following the onset of neurotoxicity, the serum ammonia level increased significantly (125.0 [111.0; 151.0] µg/dL to 148.0 [118.0; 183.0] µg/dL, p < 0.01). In conclusion, hyperammonemia cannot be assumed as the cause of neurotoxicity in glufosinate ammonium poisoning and further research is needed to examine the exact mechanism of GA poisoning.
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Dhanarisi J, Perera S, Wijerathna T, Gawarammana I, Shihana F, Pathiraja V, Eddleston M, Mohamed F. Relationship Between Alcohol Co-Ingestion and Clinical Outcome in Pesticide Self-Poisoning: A Systematic Review and Meta-Analysis. Alcohol Alcohol 2023; 58:4-12. [PMID: 36172715 DOI: 10.1093/alcalc/agac045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 08/12/2022] [Accepted: 08/13/2022] [Indexed: 01/12/2023] Open
Abstract
AIM Alcohol is a commonly co-ingested compound during self-poisoning with pesticides. Clinical experiences suggest alcohol co-ingestion (or withdrawal) makes patient management more difficult after self-poisoning and may contribute to poor clinical outcomes. We aimed to systematically review the world literature to explore the relationship between alcohol co-ingestion and outcome in pesticide self-poisoning. METHODS We searched 13 electronic databases and Google scholar, conducted citation searching and a review of reference lists to find studies which investigated the relationship of alcohol with clinical outcome of pesticide self-poisoning in different countries. Thirteen studies, including 11 case series/reports and two cohort studies were considered for inclusion. RESULTS Meta-analysis showed that alcohol co-ingestion in pesticide self-poisoning was associated with increased risk of death [odds ratio (OR) 4.9, 95% confidence interval (CI) 2.9-8.2 P<0.0001] and that alcohol co-ingested group required intubation eight times more often than non-co-ingested group in organophosphorus insecticide self-poisoning (OR 8.0, 95% CI 4.9-13.0 P<0.0001). Cases who co-ingested alcohol were older than non-alcohol group in two studies. One cohort study demonstrated that alcohol co-ingestion was associated with larger pesticide ingestions but did not itself affect the outcome. CONCLUSIONS This systematic review indicates that alcohol co-ingestion may worsen clinical outcome in pesticide self-poisoning.
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Affiliation(s)
- Jeevan Dhanarisi
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Sriyani Perera
- Medical Library, University of Peradeniya, Peradeniya, Sri Lanka
| | - Thilini Wijerathna
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.,Department of Biosystems Technology, Faculty of Technology, General Sir John Kotelawala Defence University, Rathmalana, Sri Lanka
| | - Indika Gawarammana
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.,Department of Medicine, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Fathima Shihana
- Biomedical informatics and Digital Health, Clinical Pharmacology and Toxicology Research Group, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.,The Centenary Institute of Cancer Medicine & Cell Biology, The University of Sydney, NSW, Australia
| | - Vindya Pathiraja
- Department of Pharmacy, Faculty of Allied Health Sciences, University of Ruhuna, Galle, Sri Lanka
| | - Michael Eddleston
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.,Pharmacology, Toxicology, & Therapeutics, University/BHF Centre for Cardiovascular Science, and Centre for Pesticide Suicide Prevention, University of Edinburgh, Edinburgh, UK
| | - Fahim Mohamed
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.,Department of Pharmacology, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.,National Poison Centre, Universiti Sains Malaysia, Penang Malaysia.,Department of Pharmacy, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka
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10
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Wu YK, Chang CH, Yu JH, Lan KP, Yen TH, Chang SS, Seak CJ, Chang HY, Chen HY. Intentional avermectin pesticide ingestion: a retrospective multicenter study. Clin Toxicol (Phila) 2022; 60:1099-1105. [PMID: 35916769 DOI: 10.1080/15563650.2022.2104729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 07/04/2022] [Accepted: 07/18/2022] [Indexed: 11/03/2022]
Abstract
CONTEXT Avermectin pesticides are widely used in agriculture, and are thought to have low toxicity in humans. However, information on their toxicity after accidental or deliberate ingestion is limited. OBJECTIVE The aim of this study was to evaluate the clinical manifestations of avermectin pesticide ingestion and identify factors associated with severe outcomes (death, intubation, or sustained hypotension requiring inotrope therapy). MATERIALS AND METHODS This multicenter retrospective study included patients who visited the emergency departments of six teaching hospitals due to acute avermectin pesticide ingestion between January 2012 and May 2020. Patients who reported ingestion of any other pesticides, drugs, or substances were excluded. RESULTS In total, 64 patients (median age, 72 years) were included: 60 had ingested emamectin pesticides, and 4 had ingested abamectin. Almost all (98%) were cases of self-harm. The most common presentation was drowsiness (47%), with a median Glasgow Coma Scale (GCS) score of 14, followed by shortness of breath (SOB)/dyspnea (33%) and nausea/vomiting (22%). Concurrent methanol exposure (via the solvent) was confirmed or suspected in five patients. Seventeen patients (27%) were intubated. Three patients who developed respiratory failure were not intubated because of a "do-not-resuscitate" (DNR) order. Four patients developed sustained hypotension requiring inotrope therapy. Fifty patients (78%) were admitted, of whom 27 (42%) required intensive care unit (ICU) admission. Four patients died, three of whom had a DNR order. Based on our definition, 20 patients (31%) had severe outcomes. A multivariate logistic regression model showed that a GCS score < 13 (OR 68.1, 95% CI 3.8-999) and the presence of SOB/dyspnea (OR 50.2, 95% CI 3.0-849.9) were associated with severe outcomes. CONCLUSIONS Most patients who intentionally ingested avermectin pesticides required inpatient treatment. Forty-two percent needed ICU care and 31% had severe outcomes. A GCS score < 13 and SOB/dyspnea were independently associated with severe outcomes.
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Affiliation(s)
- Yi-Kan Wu
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chia-Hau Chang
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Emergency Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan
| | - Jiun-Hao Yu
- Department of Emergency Medicine, China Medical University Hsinchu Hospital, Taiwan
| | - Kai-Ping Lan
- Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology and Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Shu-Sen Chang
- Institute of Health Behaviors and Community Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan
- Psychiatric Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chen-June Seak
- Department of Emergency Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsing-Yuan Chang
- Department of medical education, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Hsien-Yi Chen
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
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11
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Kim J, Chun BJ, Moon JM, Cho Y. Prognostic value of neutrophil to lymphocyte ratio in the diagnosis of neurotoxicity after glufosinate ammonium poisoning. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2022; 85:511-519. [PMID: 35164661 DOI: 10.1080/15287394.2022.2040670] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Neurotoxicity related to glufosinate ammonium is known to occur after a latent period of 4-60 hr following ingestion of this herbicide. However, neurotoxicity is difficult to predict in the emergency department (ED) and only a few parameters are known to be useful to indicate development of neurotoxicity. Determination of a systemic inflammation parameter such as the neutrophil to lymphocyte ratio (NLR), is a rapid and simple method which was found to be a prognostic marker in various clinical conditions such as sepsis, cardiac disorders, stroke, and cancer. Therefore, the aim of this study was to determine whether the NLR might predict neurotoxicity and be used at ED to detect neurotoxicity induced following glufosinate ammonium poisoning in admitted patients. This retrospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between January 2005 and December 2020. The primary outcome was development of neurotoxicity following acute glufosinate ammonium poisoning. Out of the 72 patients selected 44 patients (61.1%) exhibited neurotoxic symptoms. Neurotoxicity appeared with an approximate latent period of 12 hr. The NLR was significantly higher in the group displaying neurotoxicity. Multivariable analysis showed that the NLR was significant in predicting neurotoxicity. The NLR was independently associated with neurotoxicity initiated by glufosinate ammonium. Therefore, the use of the NLR might help clinically to readily and rapidly predict development of neurotoxicity associated with glufosinate ammonium at the ED.
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Affiliation(s)
- Joochan Kim
- Department of Medicine, Chonnam National University, Buk-gu, Gwangju, Republic of Korea
| | - Byeong Jo Chun
- Department of Medicine, Chonnam National University, Buk-gu, Gwangju, Republic of Korea
| | - Jeong Mi Moon
- Department of Medicine, Chonnam National University, Buk-gu, Gwangju, Republic of Korea
| | - Yongsoo Cho
- Department of Medicine, Chonnam National University, Buk-gu, Gwangju, Republic of Korea
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12
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Dobreniecki S, Mendez E, Lowit A, Freudenrich TM, Wallace K, Carpenter A, Wetmore BA, Kreutz A, Korol-Bexell E, Friedman KP, Shafer TJ. Integration of toxicodynamic and toxicokinetic new approach methods into a weight-of-evidence analysis for pesticide developmental neurotoxicity assessment: A case-study with DL- and L-glufosinate. Regul Toxicol Pharmacol 2022; 131:105167. [PMID: 35413399 DOI: 10.1016/j.yrtph.2022.105167] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 02/14/2022] [Accepted: 04/06/2022] [Indexed: 01/13/2023]
Abstract
DL-glufosinate ammonium (DL-GLF) is a registered herbicide for which a guideline Developmental Neurotoxicity (DNT) study has been conducted. Offspring effects included altered brain morphometrics, decreased body weight, and increased motor activity. Guideline DNT studies are not available for its enriched isomers L-GLF acid and L-GLF ammonium; conducting one would be time consuming, resource-intensive, and possibly redundant given the existing DL-GLF DNT. To support deciding whether to request a guideline DNT study for the L-GLF isomers, DL-GLF and the L-GLF isomers were screened using in vitro assays for network formation and neurite outgrowth. DL-GLF and L-GLF isomers were without effects in both assays. DL-GLF and L-GLF (1-100 μM) isomers increased mean firing rate of mature networks to 120-140% of baseline. In vitro toxicokinetic assessments were used to derive administered equivalent doses (AEDs) for the in vitro testing concentrations. The AED for L-GLF was ∼3X higher than the NOAEL from the DL-GLF DNT indicating that the available guideline study would be protective of potential DNT due to L-GLF exposure. Based in part on the results of these in vitro studies, EPA is not requiring L-GLF isomer guideline DNT studies, thereby providing a case study for a useful application of DNT screening assays.
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Affiliation(s)
| | | | - Anna Lowit
- Office of Pesticide Programs USEPA, Washington, DC, USA
| | - Theresa M Freudenrich
- Center for Computational Toxicology and Exposure, Office of Research and Development. US Environmental Protection Agency, Research Triangle Park, NC, USA
| | - Kathleen Wallace
- Center for Computational Toxicology and Exposure, Office of Research and Development. US Environmental Protection Agency, Research Triangle Park, NC, USA
| | - Amy Carpenter
- Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, USA
| | - Barbara A Wetmore
- Center for Computational Toxicology and Exposure, Office of Research and Development. US Environmental Protection Agency, Research Triangle Park, NC, USA
| | - Anna Kreutz
- Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, USA
| | | | - Katie Paul Friedman
- Center for Computational Toxicology and Exposure, Office of Research and Development. US Environmental Protection Agency, Research Triangle Park, NC, USA
| | - Timothy J Shafer
- Center for Computational Toxicology and Exposure, Office of Research and Development. US Environmental Protection Agency, Research Triangle Park, NC, USA.
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13
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Hsiao JT, Pan HY, Kung CT, Cheng FJ, Chuang PC. Assessment of glufosinate-containing herbicide exposure: A multi-center retrospective study. Am J Emerg Med 2021; 50:232-236. [PMID: 34392143 DOI: 10.1016/j.ajem.2021.08.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/04/2021] [Accepted: 08/06/2021] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND Exposure to glufosinate ammonium, an herbicide used worldwide, can cause CNS and respiratory toxicities. This study aimed to analyze acute human glufosinate ammonium poisoning. MATERIALS AND METHODS This multicenter retrospective cohort study involved five medical institutes affiliated with the Chang Gung Memorial Hospital system. Patients with glufosinate ammonium exposure visiting the emergency department (ED) between January 2008 and December 2020 were included. RESULTS In total, 95 patients were enrolled. Compared to exposure via the non-oral route, patients exposed orally (n = 61) had lower GCS scores, higher mortality rates, and longer hospital lengths of stay (P-value: <0.001, 0.002, and < 0.001, respectively). In the subgroup analysis among oral exposure patients, the survival group had a lower amount of estimated glufosinate ingestion than the non-survival group (10.5 [3.4-27] vs. 40.5 [27-47.3] g, P-value: 0.022), lower rate of substance co-exposure (9 [19.6%] vs. 10 [66.7%] P-value: 0.001), and lower rate of paraquat co-exposure (0 [0%] vs. 7 [46.7%] P < 0.001) compared with the mortality group. In the orally-exposed and non-paraquat co-exposure patients (n = 54), age > 70 years and GCS score < 9 at triage presented a high sensitivity (100.00%, 95% CI: 63.06-100.00%) and medium specificity (58.70%, 95% CI: 43.23-73.00%) in predicting mortality. CONCLUSION Old age, change in consciousness, and paraquat co-exposure were associated with higher mortality in human glufosinate poisoning. Age > 70 years and GCS score < 9 at triage could be predictors of mortality in patients with acute oral glufosinate poisoning.
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Affiliation(s)
- Jen-Tso Hsiao
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan
| | - Hsiu-Yung Pan
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan; Chang Gung University College of Medicine, Guishan District, Taoyuan City, Taiwan
| | - Chia-Te Kung
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan; Chang Gung University College of Medicine, Guishan District, Taoyuan City, Taiwan.
| | - Fu-Jen Cheng
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan; Chang Gung University College of Medicine, Guishan District, Taoyuan City, Taiwan.
| | - Po-Chun Chuang
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan; Chang Gung University College of Medicine, Guishan District, Taoyuan City, Taiwan.
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14
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Vodovar D, Peyre H, Mégarbane B. Relationship between acute kidney injury and mortality in poisoning - a systematic review and metanalysis. Clin Toxicol (Phila) 2021; 59:771-779. [PMID: 34080503 DOI: 10.1080/15563650.2021.1928161] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
RATIONALE Three consensus classifications of acute kidney injury have been published. These are RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease published by the Acute Dialysis Quality Initiative workgroup), AKIN (published by the Acute Kidney Injury Network) and KDIGO (published by the Kidney Disease Improving Global Outcome workgroup). Acute kidney injury has been reported consistently as associated with worsened outcomes. However, toxicant-related acute kidney injury has been excluded from the studies used to validate the classifications of acute kidney injury. OBJECTIVE To study whether poisoned patients who develop acute kidney injury, as defined by consensus definitions/classifications, have higher mortality compared to those who did not. METHODS Databases were searched from 2004 to 2019 using the following keywords (KDIGO OR "Kidney Disease: Improving Global Outcomes" OR "Kidney Disease Improving Global Outcomes" OR AKIN OR "AKI network" OR "Acute kidney Injury Network" OR ADQI OR RIFLE OR "Acute dialysis quality initiative") AND (intoxication OR poisoning OR overdose OR ingestion) AND (AKI OR kidney OR renal OR ARF). If data were available, we used a random-effects meta-analysis model and Fisher's exact test to compare mortality in patients according to kidney function definitions (acute kidney injury vs not) and stages (stages vs no acute kidney injury), respectively. If data were available, we assessed the correlation between mortality and renal function (no acute kidney injury, risk/stage 1, injury/stage 2 and failure/stage 3) using the Spearman correlation. If available, we collected the results of statistical analyses in studies that have used acute kidney injury to predict mortality. RESULTS Study selection. Thirty-three relevant studies were found, 22/33 retrospective studies (67%) and 11/33 prospective studies (33%). Paraquat was the most frequent toxicant involved (13/33, 39%). We found a disparity between studies regarding the timeframe during which mortality was assessed, the temporality of the renal function considered to predict mortality (initial/worst) and the criteria used to define/grade acute kidney injury across studies. Univariate association between acute kidney injury definitions/stages and mortality. Consensus definitions/staging of acute kidney injury were associated with higher mortality, using univariate analyses, in twenty-eight (RIFLE = 7; AKIN = 12; KDIGO = 9) studies included but not in five (AKIN = 4, KDIGO = 1). When available data were pooled, RIFLE (5 studies), AKIN (16 studies) and KDIGO definitions (8 studies) of acute kidney injury were associated with a higher mortality (Log unadjusted Odds ratios [95%-confidence interval], 2.60 [2.23; 2.97], 2.02 [1.48; 2,52] and 3.22 [2,65; 3.78], respectively). However, we found high heterogeneity (I2=54,7%) and publication bias among studies using AKIN. In ten studies with available data, the correlation between renal function (no acute kidney injury, risk/stage 1, injury/stage 2, failure/stage 3) and mortality was significant in 5 studies (RIFLE = 2; AKIN = 3), but not in five studies (RIFLE = 1; AKIN = 3; KDIGO = 1).Multivariate association between acute kidney injury definitions/stages and mortality. The definitions of acute kidney injury were associated with higher mortality in two studies (RIFLE = 2), but not in four studies (AKIN = 1 and KDIGO = 3. The stages of acute kidney injury (including one or more stages) were associated with higher mortality in four (RIFLE = 1, AKIN = 1 and KDIGO = 2). CONCLUSIONS All three consensus definitions/classifications were associated independently with increased mortality in poisoning but with disparity between studies reporting acute kidney injury.
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Affiliation(s)
- Dominique Vodovar
- Paris Poison Control Centre, Federation of Toxicology APHP, Fernand Widal Hospital, Paris, France.,University of Paris, Inserm UMRS 1144, Paris, France.,University of Paris, Medical school, Paris, France
| | - Hugo Peyre
- University of Paris, Medical school, Paris, France.,Neurodiderot. INSERM UMR 1141, Paris Diderot University, Paris, France.,Department of Child and Adolescent Psychiatry, Robert Debré Hospital, APHP, Paris, France
| | - Bruno Mégarbane
- University of Paris, Inserm UMRS 1144, Paris, France.,University of Paris, Medical school, Paris, France.,Department of Medical and Toxicological Critical Care, Federation of Toxicology APHP, Lariboisière Hospital, Paris, France
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15
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Lee HJ, Kang JH. Prolonged cognitive dysfunction in patient with splenial lesion of the corpus callosum caused by glufosinate ammonium poisoning. Turk J Emerg Med 2021; 21:82-85. [PMID: 33969245 PMCID: PMC8091998 DOI: 10.4103/2452-2473.309136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 09/05/2020] [Accepted: 09/27/2020] [Indexed: 11/11/2022] Open
Abstract
Glufosinate ammonium (GLA) is widely used as a commercial herbicide in many countries. Neurotoxicity of GLA has been associated with serious neurological complications such as loss of consciousness, convulsions, and memory impairment. Late-onset memory impairment due to GLA-induced hippocampal lesions is the most distinct clinical feature in GLA poisoning. However, the lesion of the splenium of the corpus callosum (SCC) is a rare condition in GLA poisoning, so the clinical features are not well known. We report the case of a 57-year-old male patient who developed SCC damage after GLA poisoning. The patient had various late-onset neurotoxic symptoms, including prolonged overall cognitive dysfunction and psychosis-like symptoms. Emergency physicians should be aware that GLA-induced SCC lesions may be associated with various late-onset neurotoxic symptoms.
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Affiliation(s)
- Hyun Jung Lee
- Department of Physical Medicine and Rehabilitation, Jeju National University Hospital, Republic of Korea, Korea
| | - Jeong Ho Kang
- Department of Emergency Medicine, Jeju National University School of Medicine, Republic of Korea, Korea
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16
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Severe chemical burns related to dermal exposure to herbicide containing glyphosate and glufosinate with surfactant in Korea. Ann Occup Environ Med 2020; 32:e28. [PMID: 32802344 PMCID: PMC7406703 DOI: 10.35371/aoem.2020.32.e28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 07/13/2020] [Indexed: 11/20/2022] Open
Abstract
Background Glyphosate and glufosinate use widely used as herbicide ingredients. There have been several reported cases of chemical burns caused by dermal exposure to glyphosate-containing herbicide, and patients in these cases were discharged without fatal complications. There were no cases of severe symptoms due to non-oral exposure of glufosinate-containing herbicides. Here, we report a case of fatality accompanied with severe chemical burns in an 81-year-old man who did not wash his skin for more than 48 hours after dermal exposure to herbicide containing glyphosate and glufosinate with surfactant (HGlyGluS). Case presentation An 81-year-old male with no underlying disease was admitted to the emergency department (ED). He had sprayed HGlyGluS with a manual knapsack sprayer 3 days ago and had not wash away the herbicide. On arrival, he was drowsy and had multiple severe corrosive skin lesions. Skin necrosis (10 × 15 cm) on the right shoulder and skin lesions with subcutaneous fat exposure (15 × 20 cm) on the right thigh were observed. Although he was treated including continuous renal replacement therapy, antibiotic apply, debridement operations, and so on, he was unable to recover and expired. Conclusions We suggest that prolonged dermal exposure to HGlyGluS induces fatality. Further studies including prolonged dermal exposure and ingredients of surfactants should be carried out. Also, it is necessary to educate farmers that it is very important to wash immediately after dermal exposure to pesticide.
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17
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Decreased Glucose Utilization Contributes to Memory Impairment in Patients with Glufosinate Ammonium Intoxication. J Clin Med 2020; 9:jcm9041213. [PMID: 32340163 PMCID: PMC7231126 DOI: 10.3390/jcm9041213] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/17/2020] [Accepted: 04/21/2020] [Indexed: 01/11/2023] Open
Abstract
The symptoms of glufosinate ammonium (GLA) intoxication include gastrointestinal and neurologic symptoms, respiratory failure, and cardiovascular instability. Among these, neurologic symptoms including loss of consciousness, memory impairment, and seizure are characteristic of GLA poisoning. However, the mechanism of brain injury by GLA poisoning is still poorly understood. We investigated nine patients who had performed an F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scan because of memory impairment caused by GLA ingestion. FDG-PET images of patients with GLA intoxication were compared with 24 age- and sex-matched healthy controls to evaluate whether the patients had abnormal patterns of glucose metabolism in the brain. Decreased glucose metabolism was observed in the inferior frontal and temporal lobes of these patients with GLA intoxication when compared with 24 age- and sex-matched healthy controls. Three patients performed follow-up FDG-PET scans. However, it was shown that the results of the follow-up FDG-PET scans were determined to be inconclusive. Our study showed that memory impairment induced by GLA intoxication was associated with glucose hypometabolism in the inferior frontal and temporal lobes in the brain.
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18
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Chow TYA, Chan CK, Ng SH, Tse ML. Hong Kong Poison Information Centre: Annual report 2018. HONG KONG J EMERG ME 2019. [DOI: 10.1177/1024907919893469] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Objective: The aim of this study was to report and analyse the poisoning data of Hong Kong Poison Information Centre in 2018. Methods: In 2018, all poisoning cases received by Hong Kong Poison Information Centre were retrieved from its database, Poison Information and Clinical Management System, for analysis. Results: A total of 3960 poisoned cases were analysed. There were 1770 male patients (44.7%), 2188 female patients (55.3%) and 2 sex-unspecified patients (<0.1%). The majority of cases (68.3%) were between 20 and 69 years old, and 9.9% involved children of 0–5 years old. The common causes of poisoning were suspected self-harm/suicidal attempt (36.6%), unintentional exposure (18.4%) and abusive substance use (11.1%). Excluding the common co-ingestant ethanol, the five commonest types of poison were benzodiazepines, paracetamol, Chinese herbal medicine, household products and zopiclone. Most patients were managed with supportive measures, while 13.5% and 13.7% of consultation cases were treated by decontamination and antidotes, respectively. The majority of cases had uneventful recovery; 0.8% resulted in death and 4.9% had major outcomes. A total of eight interesting cases were discussed. Conclusion: This 13th annual report provided the updated epidemiological information on poisoning pattern in Hong Kong and highlighted important changes in comparison with our previous reports.
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Affiliation(s)
- Tin Yat Anthony Chow
- Hong Kong Poison Information Centre, K3A, United Christian Hospital, Kwun Tong, Hong Kong
| | - Chi Keung Chan
- Hong Kong Poison Information Centre, K3A, United Christian Hospital, Kwun Tong, Hong Kong
| | - Sze Hong Ng
- Hong Kong Poison Information Centre, K3A, United Christian Hospital, Kwun Tong, Hong Kong
| | - Man Li Tse
- Hong Kong Poison Information Centre, K3A, United Christian Hospital, Kwun Tong, Hong Kong
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19
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Lee J, Lee Y, Kim YS, Choi JG, Go TH, Kim H, Cha YS. Serum ammonia as an early predictor of in-hospital mortality in patients with glufosinate poisoning. Hum Exp Toxicol 2019; 38:1007-1013. [DOI: 10.1177/0960327119855124] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background: The mortality rate associated with human glufosinate poisoning is high. We evaluated the usefulness of serum ammonia and sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores for early prediction of in-hospital mortality in glufosinate ammonium poisoning. Methods: A prospectively collected pesticide poisoning registry at a single academic medical center was retrospectively analyzed. Data were collected from consecutive patients diagnosed with glufosinate ammonium poisoning between May 2007 and February 2018. The initial serum ammonia level was defined as the highest serum ammonia level measured within 12 h after emergency department (ED) arrival. The SOFA and APACHE II scores were calculated using data obtained within the first 12 h after ED arrival. The patients were divided into survivor and nonsurvivor groups by in-hospital death status. Results: In total, 110 patients were included. Ten patients (9.1%) died in the hospital despite treatment. Median initial serum ammonia level was significantly higher in the nonsurvivor group than in the survivor group (219 (range: 158–792) versus 100.5 (range: 25–317) µg/dL, p < 0.001). Median SOFA and APACHE II scores in the survivor and nonsurvivor groups were 2 (range: 0–10) versus 5 (range: 1–8) ( p = 0.044) and 7 (range: 0–28) versus 16 (range: 8–22) ( p = 0.001), respectively. In the multiple logistic regression analysis, the initial serum ammonia level was the only independent predictor (cutoff value: 151 µg/dL). Conclusion: An initial serum ammonia level >151 µg/dL was an independent early predictor of in-hospital mortality in glufosinate ammonium poisoning.
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Affiliation(s)
- J Lee
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Y Lee
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - YS Kim
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - JG Choi
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - TH Go
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - H Kim
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - YS Cha
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
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Izumi H, Ishimoto T, Yamamoto H, Mori H. Bioluminescence imaging of Arc expression in mouse brain under acute and chronic exposure to pesticides. Neurotoxicology 2019; 71:52-59. [DOI: 10.1016/j.neuro.2018.12.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 11/27/2018] [Accepted: 12/13/2018] [Indexed: 11/28/2022]
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21
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Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice. Neurotoxicology 2018; 69:152-163. [DOI: 10.1016/j.neuro.2018.10.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 09/13/2018] [Accepted: 10/01/2018] [Indexed: 12/22/2022]
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22
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Masiol M, Giannì B, Prete M. Herbicides in river water across the northeastern Italy: occurrence and spatial patterns of glyphosate, aminomethylphosphonic acid, and glufosinate ammonium. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2018; 25:24368-24378. [PMID: 29948720 DOI: 10.1007/s11356-018-2511-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 06/05/2018] [Indexed: 05/27/2023]
Abstract
Glyphosate and glufosinate ammonium are the active ingredients of commonly used herbicides. Active agricultural lands extend over a large part of the Veneto region (Eastern Po Valley, Italy) and glyphosate and glufosinate ammonium are widely used. Consequently, surface waters can be potentially contaminated. This study investigates the occurrence of glyphosate and glufosinate ammonium as well as aminomethylphosphonic acid (AMPA, the degradation product of glyphosate) in river water of Veneto. Eighty-six samples were collected in 2015 at multiple sampling points across the region. Samples were analyzed for the two target herbicides, AMPA as well as for other variables, including water temperature, pH, dissolved oxygen, conductivity, hardness, BOD, COD, inorganic ions, total nitrogen, total phosphorus, total suspended solids, arsenic, and lead. The average concentrations (all samples) were 0.17, 0.18, and 0.10 μg L-1 for glyphosate, AMPA, and glufosinate ammonium, respectively. The European upper tolerable level for pesticides (annual average 0.1 μg L-1) was often exceeded. Chemometric analysis was therefore applied to (i) investigate the relationships among water pollutants, (ii) detect the potential sources of water contamination, (iii) assess the effective water pollution of rivers by identifying river basins with anomalous pollution levels, and (iv) assess the spatial variability of detected sources. Factor analysis identified four factors interpreted as potential sources and processes (use of herbicides, leaching of fertilizers, urban/industrial discharges, and the biological activity on polluted or stagnant waters). A discriminant analysis revealed that the pollution from anthropogenic discharges is homogeneously present in surface water of Veneto, while biological activity and fertilizers present heterogeneous distributions. This study gives insights into the concentrations of herbicides in rivers flowing through a wide region that has heavy use of these chemicals in agriculture. The study also points out some hot-spots and suggests the future implementation of the current monitoring protocols and network.
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Affiliation(s)
- Mauro Masiol
- Department of Public Health Sciences, University of Rochester Medical Center, 265 Crittenden Boulevard, CU 420644, Rochester, NY, 14642, USA.
| | - Biagio Giannì
- Dipartimento Regionale Laboratori, Agenzia Regionale per la Prevenzione e Protezione Ambientale del Veneto (ARPAV), 31100, Treviso, Italy
| | - Marco Prete
- Dipartimento Regionale Laboratori, Agenzia Regionale per la Prevenzione e Protezione Ambientale del Veneto (ARPAV), 31100, Treviso, Italy
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23
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Lee JH, Kim YW. Prognostic factor determination mortality of acute glufosinate-poisoned patients. Hum Exp Toxicol 2018; 38:129-135. [DOI: 10.1177/0960327118783534] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Glufosinate-containing herbicide is increasingly used in agriculture. Its poisoning is a worldwide concern. More and more patients are poisoned by glufosinate. The aim of this study was to determine the factors associated with mortality of patients with acute poisoning of glufosinate. Methods: This was a retrospective cohort study conducted from January 1998 to October 2015. Using a multivariate logistic analysis, data for the total population were retrospectively analyzed to determine the factors associated with mortality. Various variables were compared in survivors and non-survivors. Significant predictive variables, Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system, the Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA) score were compared by analyzing receiver operating characteristic (ROC) curves. Results: A total of 253 patients (mean age: 58 years) were enrolled. Of the 253 patients, 219 (86.6%) survived and 34 (13.4%) died. Decreased Glasgow Coma Scale (GCS) and bicarbonate (HCO3−), use of mechanical ventilator, and use of vasopressors (dopamine, dobutamine, norepinephrine) were associated with mortality. The areas under the curve in the ROC curve analysis for the predictive variables, SOFA score, APACHE II scoring system, and SAPS II were 0.952, 0.829, 0.927, and 0.944, respectively. Conclusion: Four predictive variables (GCS < 9, HCO3− < 16.0 mmol/L, mechanical ventilator apply, and use of vasopressors) were associated with mortality in the total population of patients with acute poisoning of glufosinate. These predictive variables had good discriminative power for predicting mortality of patients with acute poisoning of glufosinate-containing herbicide compared to APACHE II, SOFA, and SAPS II.
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Affiliation(s)
- JH Lee
- Department of Emergency Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - YW Kim
- Department of Emergency Medicine, Inje University College of Medicine, Busan, Republic of Korea
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Jeon U, Park S, Park S, Lee EY, Gil HW. Clinical characteristics of stress cardiomyopathy in patients with acute poisoning. Sci Rep 2018; 8:223. [PMID: 29317766 PMCID: PMC5760562 DOI: 10.1038/s41598-017-18478-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 12/12/2017] [Indexed: 12/12/2022] Open
Abstract
Patients who attempt intentional suicide suffer from physical or emotional stress. This situation might be an important factor that causes takotsubo cardiomyopathy. We retrospectively investigated the clinical features of Takotsubo cardiomyopathy in patients with acute poisoning. This study included patients who were admitted from January 2010 to December 2015 because of intentional poisoning by ingestion. Among these patients, we selectively collected data of patients who underwent an echocardiogram. We divided the patients into three groups according to the echocardiogram; the non-cardiomyopathy group, the global hypokinesia group, and the takotsubo cardiomyopathy group. One hundred forty-seven patients were analyzed in this study. One hundred thirty-one patients had normal cardiac function without regional wall motion abnormality. Global hypokinesia was observed in five patients. The overall incidence of takotsubo cardiomyopathy was 7.5% (11/147). Levels of cardiac enzymes including CK-MB, Troponin T, a marker of cardiac muscle ischemia, were higher in the global hypokinesia group and the takotsubo cardiomyopathy group compared with the non-cardiomyopathy group. The most commonly consumed poison was organophosphate in the takotsubo cardiomyopathy group. In conclusion, takotsubo cardiomyopathy may be one of the cardiac complications in patients who attempt suicide by consuming a poison.
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Affiliation(s)
- Ung Jeon
- Department of Internal medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Samel Park
- Department of Internal medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - SangHo Park
- Department of Internal medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Eun-Young Lee
- Department of Internal medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Hyo-Wook Gil
- Department of Internal medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.
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Cha YS, Kim H, Lee Y, Choi EH, Kim HI, Kim OH, Cha KC, Lee KH, Hwang SO. The relationship between serum ammonia level and neurologic complications in patients with acute glufosinate ammonium poisoning: A prospective observational study. Hum Exp Toxicol 2017; 37:571-579. [DOI: 10.1177/0960327117715902] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Glufosinate ammonium poisoning can cause neurological complications even after a symptom-free period. We prospectively investigated the predictors of neurologic complications in acute glufosinate ammonium poisoning and the change of serum ammonia level as a predictor of patient’s presence and recovery of neurologic complication. This prospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between September 2014 and June 2016. Serum ammonia was serially measured. The patients were divided into two groups: the neurologic complication group and the nonneurologic complication group. We also defined 25 other insecticide- or herbicide-poisoned patients as controls. The neurologic complication group included 18 patients (72.0%). The latency period for neurologic complications was within 48-h postingestion. The peak ammonia level was statistically higher in the neurologic complication group than in the control group ( p < 0.001) and the nonneurologic complication groups ( p = 0.001). There was a statistical difference between the nonneurologic complication group and the neurologic complication group ( p = 0.0085) in terms of ingested amount. The peak ammonia was the only predictor for the development of neurologic complications (the optimal cutoff: 90 μg/dL). In patients with mental changes, the mean serum ammonia levels before and after recovery of the mental changes were statistically different ( p = 0.0019). In acute glufosinate ammonium poisoning, serial serum ammonia level measurements are needed and a serum peak ammonia level greater than 90 μg/dL is a predictor of neurologic complications. Also, it is important to treat the hyperammonemia in acute glufosinate ammonium poisoning.
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Affiliation(s)
- YS Cha
- Department of Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - H Kim
- Department of Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - Y Lee
- Department of Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - EH Choi
- Biostatistician, Institute of Lifestyle Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - HI Kim
- Department of Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - OH Kim
- Department of Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - K-C Cha
- Department of Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - KH Lee
- Department of Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - SO Hwang
- Department of Emergency Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
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Kavousi-Gharbi S, Jalli R, Rasekhi-Kazerouni A, Habibagahi Z, Marashi SM. Discernment scheme for paraquat poisoning: A five-year experience in Shiraz, Iran. World J Exp Med 2017; 7:31-39. [PMID: 28261553 PMCID: PMC5316902 DOI: 10.5493/wjem.v7.i1.31] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 01/05/2017] [Accepted: 01/18/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate various schemes for paraquat poisoning and different variables that influence the outcome of acute paraquat poisoning.
METHODS In a cross-sectional study, the information about all cases of acute paraquat poisoning who were admitted to teaching hospitals affiliated to Shiraz University of Medical Sciences, in a five year period (September 2010 to September 2015) were evaluated. The variables included: Demographic data, medical assessment, therapeutic options, laboratory findings, and the outcomes. Data were analyzed using SPSS, version 22. Significant difference between groups was tested using t-test for continues outcomes and χ2 test for categorical. The significance level was considered to be P < 0.05.
RESULTS A total of 104 patients (66.3% male) were evaluated. The mean age of the female patients was 22.81 ± 9.87 years and the male patients’ was 27.21 ± 11.06 years. Ninety seven (93.3%) of all the cases were suicide attempts with mortality rate of 43.2%. Despite the necessity for emergency hemodialysis during the first 6 h of intoxication, none of the patients had dialysis during this time. Immunosuppressive and corticosteroid medications were not administrated in adequate dosage in 31.1% and 60% of the patients, respectively. Ingestion of more than 22.5 cc of paraquat and increase in creatinine level were the most important predictors of mortality.
CONCLUSION Treatment should start immediately for these patients. Moreover, creating a clinical guideline according to the findings can have an impact on the treatment procedure which seems to be necessary.
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Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium. Neuroreport 2016; 27:532-41. [PMID: 27031874 DOI: 10.1097/wnr.0000000000000578] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.
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Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation. Clin Sci (Lond) 2016; 130:1939-54. [PMID: 27549113 DOI: 10.1042/cs20160530] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 08/22/2016] [Indexed: 11/17/2022]
Abstract
Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1β (IL-1β) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice.
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Moreira C, Ramos MJ, Fernandes PA. Glutamine Synthetase Drugability beyond Its Active Site: Exploring Oligomerization Interfaces and Pockets. Molecules 2016; 21:E1028. [PMID: 27509490 PMCID: PMC6274088 DOI: 10.3390/molecules21081028] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 08/01/2016] [Accepted: 08/04/2016] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Glutamine synthetase (GS) is a crucial enzyme to the nitrogen cycle with great commercial and pharmaceutical value. Current inhibitors target the active site, affecting GS activity indiscriminately in all organisms. As the active site is located at the interface between two monomers, the protein-protein interface (PPI) of GSs gains a new role, by providing new targets for enzyme inhibition. Exploring GSs PPI could allow for the development of inhibitors selective for specific organisms. Here we map the PPI of three GSs-human (hsGS), maize (zmGS) and Mycobacterium tuberculosis (mtGS)-and unravel new drugable pockets. METHODS The PPI binding free energy coming from key residues on three GSs from different organisms were mapped by computational alanine scan mutagenesis, applying a multiple dielectric constant MM-PBSA methodology. The most relevant residues for binding are referred as hot-spots. Drugable pockets on GS were detected with the Fpocket software. RESULTS AND CONCLUSIONS A total of 23, 19 and 30 hot-spots were identified on hsGS, zmGS and mtGS PPI. Even possessing differences in the hot-spots, hsGS and zmGS PPI are overall very similar. On the other hand, mtGS PPI differs greatly from hsGS and zmGS PPI. A novel drugable pocket was detected on the mtGS PPI. It seems particularly promising for the development of selective anti-tuberculosis drugs given its location on a PPI region that is highly populated with hot-spots and is completely different from the hsGS and zmGS PPIs. Drugs targeting this pockets should be inactive on eukaryotic GS II enzymes.
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Affiliation(s)
- Cátia Moreira
- UCIBIO, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal.
| | - Maria J Ramos
- UCIBIO, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal.
| | - Pedro A Fernandes
- UCIBIO, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal.
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Lee DK, Youk H, Kim H, Kim OH, Go J, Kim TH, Cha K, Lee KH, Hwang SO, Cha YS. Initial Serum Ammonia as a Predictor of Neurologic Complications in Patients with Acute Glufosinate Poisoning. Yonsei Med J 2016; 57:254-9. [PMID: 26632409 PMCID: PMC4696962 DOI: 10.3349/ymj.2016.57.1.254] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 03/11/2015] [Accepted: 03/17/2015] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Glufosinate poisoning can cause neurologic complications that may be difficult to treat due to delayed manifestation. Studies assessing possible predictors of complications are lacking. Although serum ammonia level is a potential predictor of severe neurotoxicity, it has only been assessed via case reports. Therefore, we investigated factors that predict neurologic complications in acute glufosinate-poisoned patients. MATERIALS AND METHODS We conducted a retrospective review of 45 consecutive glufosinate-poisoning cases that were diagnosed in the emergency department (ED) of Wonju Severance Christian Hospital between May 2007 and July 2014. Patients with a Glasgow Coma Scale (GCS) score of <8, seizure, and/or amnesia were defined to a neurologic complication group. RESULTS The neurologic complication group (29 patients, 64.4%) comprised patients with GCS<8 (27 patients, 60.0%), seizure (23 patients, 51.1%), and amnesia (5 patients, 11.1%). Non-neurologic complications included respiratory failure (14 patients, 31.1%), intubation and ventilator care (23 patients, 51.1%), shock (2 patients, 4.4%), pneumonia (16 patients, 35.6%), acute kidney injury (10 patients, 22.2%), and death (4 patients, 8.9%). Complications of GCS<8, seizure, respiratory failure, and intubation and ventilator care appeared during latent periods within 11 hrs, 34 hrs, 14 hrs, and 48 hrs, respectively. Initial serum ammonia was a predictor of neurologic complications [odds ratio 1.039, 95% confidence interval (1.001-1.078), p=0.046 and area under the curve 0.742]. CONCLUSION Neurologic complications developed in 64.4% of patients with acute glufosinate poisoning. The most common complication was GCS<8. Initial serum ammonia level, which can be readily assessed in the ED, was a predictor of neurologic complications.
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Affiliation(s)
- Dong Keon Lee
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Hyun Youk
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Hyun Kim
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Oh Hyun Kim
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Jin Go
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Tae Hoon Kim
- Department of Emergency Medicine, Busan Baik Hospital, Inje University, Busan, Korea
| | - Kyoungchul Cha
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Kang Hyun Lee
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Sung Oh Hwang
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Yong Sung Cha
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea.
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Moon JM, Chun BJ. Serial ammonia measurement in patients poisoned with glufosinate ammonium herbicide. Hum Exp Toxicol 2015; 35:554-61. [DOI: 10.1177/0960327115595688] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
This study investigated whether ammonia concentrations can predict delayed neurotoxicity development and neurotoxicity latency in glufosinate ammonium (GLA) herbicide-poisoned patients presenting with an alert mental state and stable hemodynamics. This retrospective observational case study included 26 patients divided into 2 groups: neurotoxicity during hospitalization (complicated group) and without neurotoxicity (noncomplicated group). Thirteen patients (50.0%) experienced neurotoxicity at 16 h post-ingestion. Although ammonia concentrations at presentation did not differ significantly between the two groups, the ammonia level in the complicated group increased significantly at the next measurement and remained significantly higher than that in the noncomplicated group until 48 h after ingestion. The peak ammonia concentration before neurotoxicity development was an independent predictor of neurotoxicity (odds ratio: 1.047, 95% confidence interval: 1.010–1.087, p value = 0.014), and the optimal cutoff value of peak ammonia concentration for predicting neurotoxicity was 101.5 μg/dL. The rate of ammonia increase was not associated with the time latency from ingestion to neurotoxicity development. This study showed that serial ammonia measurements in GLA-poisoned patients may identify those who are at high risk of developing neurotoxicity. However, as this study enrolled few patients, further qualified trials are required to confirm our results and to reveal the etiology of hyperammonemia and its causality in neurotoxicity.
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Affiliation(s)
| | - BJ Chun
- Department of Emergency Medicine, Chonnam National University Medical School, Gwangju, South Korea
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Park JS, Kwak SJ, Gil HW, Kim SY, Hong SY. Glufosinate herbicide intoxication causing unconsciousness, convulsion, and 6th cranial nerve palsy. J Korean Med Sci 2013; 28:1687-9. [PMID: 24265537 PMCID: PMC3835516 DOI: 10.3346/jkms.2013.28.11.1687] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2013] [Accepted: 05/15/2013] [Indexed: 11/20/2022] Open
Abstract
Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.
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Affiliation(s)
- Jae-seok Park
- Department of Internal Medicine, Soonchunhyang University, College of Medicine, Cheonan, Korea
| | - Soo-Jung Kwak
- Department of Internal Medicine, Soonchunhyang University, College of Medicine, Cheonan, Korea
| | - Hyo-wook Gil
- Department of Internal Medicine, Soonchunhyang University, College of Medicine, Cheonan, Korea
| | - So-Young Kim
- Department of Ophthalmology, Soonchunhyang University, College of Medicine, Cheonan, Korea
| | - Sae-yong Hong
- Department of Internal Medicine, Soonchunhyang University, College of Medicine, Cheonan, Korea
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Inoue Y, Onodera M, Fujita Y, Fujino Y, Kikuchi S, Endo S. Factors associated with severe effects following acute glufosinate poisoning. Clin Toxicol (Phila) 2013; 51:846-9. [PMID: 24044532 DOI: 10.3109/15563650.2013.841180] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CONTEXT In acute glufosinate poisoning, sudden respiratory arrest and convulsion can occur after a latent period of 4-60 h. There is still no factor that accurately predicts the occurrence of these symptoms. OBJECTIVE To elucidate the predictors of severe effects following acute glufosinate poisoning. MATERIALS AND METHODS This study is a retrospective observational case series. The subjects were 16 patients who had acute glufosinate poisoning. They were divided into a group with respiratory arrest or convulsion during hospitalization (severe group) and a group without (non-severe group). The following characteristics (or predictors) were compared between the groups: age, sex, calculated amount of glufosinate (volume of ingested poison (glufosinate-containing herbicide) × glufosinate concentration of the product), time duration from poison ingestion to arrival at our hospital, use of gastric lavage, use of whole bowel irrigation, Glasgow Coma Scale, laboratory parameters, PaO₂/FiO₂ ratio (P/F ratio), shock index, and presence or absence of systemic inflammatory response syndrome (SIRS) on arrival. RESULTS The P/F ratio was significantly lower in the severe group than in the non-severe group (median, 287.5 vs. 409.0; P = 0.049). The receiver operating characteristic (ROC) curve was plotted for the predictor of increasing severity based on the P/F ratio. The area under the curve was 0.714, and the optimal cutoff point for increasing severity was 374.0. The sensitivity was 75.0%, specificity of 71.4%, and accuracy of 75.0%. The shock index was significantly higher (median, 0.52 vs. 0.41; P = 0.031). Significantly more patients had SIRS in the severe group than in the non-severe group (P = 0.015). Logistic regression analysis was performed with a backward elimination procedure. SIRS was selected as the independent predictor of increasing severity (odds ratio, 29.810; 95% confidence interval, 1.011-878.952; P = 0.049). DISCUSSION AND CONCLUSION Severe effects following acute glufosinate poisoning were associated with two positive SIRS criteria. A low P/F ratio may be useful for predicting the occurrence of respiratory complications.
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Affiliation(s)
- Y Inoue
- Department of Emergency Medicine, Iwate Medical University, School of Medicine , Morioka, Iwate , Japan
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Peltzer PM, Junges CM, Attademo AM, Bassó A, Grenón P, Lajmanovich RC. Cholinesterase activities and behavioral changes in Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed to glufosinate ammonium herbicide. ECOTOXICOLOGY (LONDON, ENGLAND) 2013; 22:1165-1173. [PMID: 23868463 DOI: 10.1007/s10646-013-1103-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/09/2013] [Indexed: 06/02/2023]
Abstract
In this study, amphibian tadpoles of Hypsiboas pulchellus were exposed to herbicide Liberty®, which contains glufosinate ammonium (GLA), for 48 h to the following concentrations: 0 (control), 3.55, 4.74, 6.32, 8.43, 11.25, 15, 20, 26.6, and 35.5 mg GLA L(-1). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, as well as swimming capabilities (swimming speed and mean distance) were measured in tadpoles whose concentrations displayed survival rates > 85 %. Our results reveal that sublethal concentrations of GLA significantly inhibited both AChE and BChE activities in tadpoles with respect to the control, showing a concentration-dependent inhibitory effect. The highest inhibition percentages of AChE (50.86%) and BChE (53.02%) were registered in tadpoles exposed to 15 mg GLA L(-1). At this concentration, a significant increase of the swimming speed and mean distance were found in exposed tadpoles with respect to the control, as well as a negative and significant correlation between swimming speed and BChE activity, thus suggesting that this enzyme inhibition is related to an increase in swimming speed. Therefore, exposure of tadpoles to GLA in the wild at concentrations similar to those tested here may have adverse consequences at population level because neurotransmission and swimming performance are essential for tadpole performance and survival.
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Affiliation(s)
- Paola M Peltzer
- National Council for Scientific and Technical Research (CONICET), Buenos Aires, Argentina
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