• Journal of the Korea Institute of Military Science and Technology
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• v.16 no.2
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• pp.218-224
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• 2013

Organophosphorus compounds are irreversible inhibitors of cholinesterase enzyme. Exposure causes a progression of toxic signs, including hypersecretion, tremor, convulsion, respiratory distress, epileptiform seizure, brain injuries and death. To protect brain injuries, administration of diazepam as a neuroprotectant is now considered essential for severely exposed nerve agent casualties. However, studies have shown diazepam to provide less than total protection against the neuropathological consequences of nerve agent exposure. In this context, extensive studies have been carried out to find out effective alternative drugs to protect brain from epileptiform seizures induced by organophosphate compounds intoxication. It has been reported that a combination of carbamate and anticholinergic or antiglutamatergic can be a very effective medical countermeasure in dealing with the threat of organophosphorous poisoning. In this study, experimental animals including rats and guinea pigs were implanted with microelectrodes on their brain sculls, and treated with various centrally acting drugs such as physostigmine and procyclidine prior to soman challenge, and then its electroencephalography(ECoG) was monitored to see anticonvulsant effects of the drugs. It was found that seizure activities in ECoG were not always in proportion to clinical signs induced by soman intoxication, and that combinative pretreatment with physostigmine plus procyclidine effectively stopped the seizures induced by organophosphorous poisoning.

• Journal of Apiculture
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• v.34 no.4
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• pp.305-313
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• 2019

Honey bees (Apis mellifera) forage in agricultural areas, and are exposed to diverse pesticide poisoning. Toxic effects on Apis mellifera of different groups of pesticides were tested in the laboratory; fungicide (Metconazole), herbicide (Glyphosate), acaricide (Amitraz), organophosphate insecticide(Fenitrothion) and neonicotinoid insecticides(Thiacloprid, Thiamethoxam, Imidacloprid, Acetamiprid, Dinotefuran and Clothianidin). Commercial formulations were serially diluted from the recommended concentration (RC) to 10-6 times to carry out feeding and contact tests. Toxicity was transformed into lethal dose (LD50) and hazard question (HQ). The acute toxicity of pesticides showed similar patterns between feeding and contact tests. But feeding tests showed greater toxic to honey bee than contact test. The organophosphate and nitro-neonicotinoid insecticides were highly toxic with HQ values ranging greater than 1. However, cyano-neonicotinoids of Thiacloprid and Acetamiprid showed low toxicity. Even at the RC, 24 hr mortalities were 18 and 30%. The acaricide (Amitraz) showed intermediate level of toxicity at RC but negligible at the concentration lower than 10-1 times. A fungicide(Metconazole) and herbicide(Glyphosate) showed minimal impacts. The results imply that the selective use of pesticides could help conservation of pollinators in agricultural production systems.

• Journal of The Korean Society of Clinical Toxicology
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• v.5 no.1
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• pp.74-78
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• 2007

The carbamates are a group of insecticides derived from carbamic acid, with a broad spectrum of uses as agricultural and household garden insecticides. Carbamate insecticides are reversible cholinesterase inhibitors. Their inhibitory action is mediated by reversible carbamylation of acetylcholine, as with the organophosphate insecticides. Carbamates are absorbed by the body through multiple routes, including inhalation, ingestion, and dermal absorption. Although poisoning can result from occupational exposure or accidental ingestion, in most cases there is suicidal intent. This is particularly true in developing countries, where the highest incidence of morbidity and mortality from this cause occurs. Cardiac complications often accompany poisoning by carbamate compounds, which may be serious and often fatal. The extent, frequency, and pathogenesis of cardiac toxicity from carbamate compounds has not been clearly defined. Possible mechanismsinclude sympathetic and parasymphatetic overactivity, hypoxemia, acidosis, electrolyte derangements, and a direct toxic effect of the compounds on the myocardium. Patients with carbamate poisoning should immediately be transferred to an intensive or coronary care unit where appropriate monitoring and resuscitative facilities are available. We here report a case of acute coronary syndrome resulting from acute carbamate ingestionthat resulted in a healthy discharge.

• Journal of The Korean Society of Clinical Toxicology
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• v.12 no.2
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• pp.77-84
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• 2014

Purpose: Carbamate insecticides are potent cholinesterase inhibitors capable of causing severe cholinergic toxicity. Use of carbamate rather than organophosphate insecticides has been increasing. Compared with organophosphate poisoning, relatively few studies have investigated carbamate-associated acute pancreatitis. We investigated general characteristics and pancreatitis of carbamate poisoning and the predictors, among those readily assessed in the emergency department. Methods: We performed a retrospective review of consecutive patients, aged over 18 years, who were admitted between January 2008 and April 2012 to an emergency department (ED) of an academic tertiary care center for treatment of carbamate poisoning. Patients who exhibited poisoning by any other material, except alcohol, were excluded. After application of exclusion criteria, patients were divided according to carbamate-induced pancreatitis and non-pancreatitis groups. Results: A total of 41 patients were included in this study. Among these 41 patients, the prevalence of acute pancreatitis was 36.6% (15 patients). Initial blood chemistry tests showed a statistically higher glucose level in the pancreatitis group, compared with the non-pancreatitis group (222, IQR 189-284 vs. 137, IQR 122-175 mg/dL, P<0.05). Regarding clinical courses and outcomes, a significantly higher proportion of patients developed pneumonia [10 (66.7%) vs. 6 (23.1%), P<0.05] and had a longer hospital stay (7 days, IQR 6-12 vs. 5 days, IQR 2-11, P<0.05), but no difference in mortality, in the pancreatitis group vs. the non-pancreatitis group. In multivariate analysis, the initial glucose was showing significant association with the presentation of carbamate-induced acute pancreatitis (odds ratio 1.018, 95% confidence interval 1.001-1.035, P<0.05). Conclusion: Carbamate-induced acute pancreatitis is common, but not fatal. Initial serum glucose level is associated with acute pancreatitis.

• Journal of The Korean Society of Clinical Toxicology
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• v.5 no.1
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• pp.8-14
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• 2007

Purpose: Organophosphorus insecticides tend to be regarded as a homogeneous single entity. We aimed to determine whether organophosphate poisoning differs by subgroups in clinical features and severity. Methods: We retrospectively reviewed medical records of all patients with acute organophophorus poisoning from January 1998 to December 2006. We investigated clinical features, Glasgow coma scale (GCS), laboratory findings, QTc intervals, management, and outcomes. Results: A total of 109 patients were included. The dimethoxy group experienced significantly longer times than the diethoxy group for ventilation duration (0.6 day vs. 0.2 day, p=0.006), ICU duration (2.0 day vs. 0.8 day, p=0.037), and total admission duration (2.8 day vs. 0.9 day, p=0.008), except in cases of dichlorvos poisoning. Also, the GCS of the dimethoxy group (except with dichlorvos) was significantly lower than for the diethoxy group (dimethoxy, $11.2{\pm}5.2$ vs. diethoxy, $13.8{\pm}2.4$, p= 0.021). QTc intervals for the dimethoxy group (except with dichlorvos) tended to be somewhat greater than for the diethoxy group (dimethoxy, $452.9{\pm}16.1\;msec$ vs. diethoxy, $429.6{\pm}40.9\;msec$). There were 65 patients with dichlorvos ingestion, and 2 of these patients (3%) died. Conclusion: When compared to the diethoxy group, the dimethoxy group of organophosphates (with the exception of dichlorvos) were associated with poorer prognostic value for indicators such as GCS, QTc interval, requirement for intubation, ICU duration, and total admission duration. Within the dimethoxy group, patients with dichlorvos poisoning had relatively better prognoses than for the other dimethoxy group organophosphates studied.

• Toxicological Research
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• v.16 no.3
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• pp.195-200
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• 2000

Antidotal efficacy of physostigmine plus procyclidine, the combinational prophylactics for organophosphate poisoning, was evaluated in rats and guinea pigs. To assess the dose-response relation-ship in rats, various doses (0.3-6.0mg/kg) of procyclidine in combination with a fixed dose (0.1mg/kg) of physostigmine were pretreated subcutaneously 30 min prior to subcutaneous exposure to nerve-agents. Physostigmine alone exerted protection ratios of 2.44, 1.20, 1.50, 1.50 and 2.20 folds for tabun, sarin, soman, cyclosarin and V-agent, respectively. Interestingly, coadmnistration of procyclidine with physostigmine exhibited remarkable synergistic effects in a dose-dependent manner, leading to 4.00~8.00 folds for tabun, 2.15-8.50 folds for sarin, 1.92~507 folds for so man, 2.15~2.90 folds for cyclosarin, and 2.71~10.50 folds for V-agent. On the contrary, a low effect (l.65 fold) was achieved with the traditional antidotes atropine (17.4 mg/kg) plus 2-pralidoxime (30 mg/kg) treated immediately after soman poisoning. Noteworthy, the combinational prophylactics markedly potentiated the effect of atropine plus 2-pralidoxime to 6.13 and 12.27 folds with 1.0 and 3.0 mg/kg of procyclidine, respectively, against soman poisoning. In guinea pigs, the physostigmine plus procyclidine prophylactics exerted protective effects of 3.00~4.70 folds against soman intoxcation, which were much higher at low doses (0.3~1.0 mg/kg) of procyclidine than those in rats. Taken together, it is proposed that the combinational prophylactics composed oj physostigmine and procyclidine could be a promising antidote regimen for the poisoning with organophosphates possessing diverse properties.

• Environmental Analysis Health and Toxicology
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• v.25 no.4
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• pp.263-271
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• 2010

Objectives : The records of 447 pesticide poisoning deaths from the National Forensic Service (NFS) headquarters located in Seoul of Korea from 2005 to 2009 were retrospectively reviewed. Methods : The data of each case were analyzed by using the SPSS program. Results : The mean age was $57.8{\pm}14.8$ years and the range was 16-92 years. The numbers of deaths of males and females were 301 and 134, respectively. The largest number of cases occurred in people aged 50-59 years (n=92, 20.6%) followed by the age groups 40-49 years (n=91, 20.4%), 60-69 years (n=88, 19.7%), and 70-79 years (n=75, 16.8%). The total number of deaths among other age groups (10-19, 20-29, 30-39, 80-89, and 90-99 years) was 73, representing only 16.3%. Of all pesticide poisoning deaths, 96.2% were due to suicide, and 28.4% of the total number who died received medical treatment. The mostfrequent site of ingestion was the person's own residence (n=279, 62.4%). The most common classes of pesticide were bipyridylium herbicide (paraquat, 31.1%), organophosphate insecticide (21.7%), and carbamate insecticide (15.4%). The major pesticides having a high proportion of fatalities were paraquat (31.1%), methomyl (11.4%), glyphosate (9.1%), dichlorvos (5.6%), phosphamidon (4.6%), and methidathion (4.0%). Conclusions : This study showed that poisoning deaths due to pesticides are one of the major public health problems in Korea. Enforcement of regulations and safety education to prevent pesticide poisoning should be carried out by the government.

• Korean Journal of Veterinary Research
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• v.58 no.3
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• pp.167-170
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• 2018

Two 12-month-old cattle with anthelmintics containing trichlorfon the day before death presented to the Animal and Plant Quarantine Agency for diagnosis. In necropsy, they revealed enlargement of the spleens, redness of mucosa and serosa in stomachs and intestines, and friable kidneys. Histopathologically, hemorrhages in the spleens, omasums, abomasums, and intestines as well as renal tubular necrosis were observed. Trichlorfon was detected at above the lethal dose in the ruminal contents. Based on these findings, we diagnosed this case as death caused by trichlorfon poisoning.

• Journal of The Korean Society of Clinical Toxicology
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• v.13 no.2
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• pp.55-61
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• 2015

Purpose: Many studies have examined the mechanisms of impaired glucose homeostasis after organophosphate (OP) exposure, however no study has evaluated the clinical utility of blood glucose measurements in patients with OP poisoning. The current study was conducted to evaluate the initial glucose level at presentation and the glycemic variables during the first 3 days after admission as a predictor of mortality. Methods: This retrospective observational case series included 228 patients with a history of OP poisoning. Among other clinical data, information on the initial glucose level at presentation and mean glucose level, delta glucose level, and the presence of a hypoglycemic event during the first 3 days of admission, was collected. Results: Survivors had lower initial glucose levels at presentation and glucose variability during the first 3 days of admission compared to non-survivors. The frequency of hypoglycemic events was higher in non-survivors. In multivariate analysis, the initial glucose level (> 233 mg/dl) was an independent predictor of mortality, along with age. Conclusion: The initial glucose level at presentation can be helpful in prediction of mortality in cases of OP intoxication at bedside. The physician should pay attention to patients with a glucose level >233 mg/dl at presentation after ingestion of OP.

• Toxicological Research
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• v.13 no.3
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• pp.215-222
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• 1997

The features of seizure-related brain injuries in rats poisoned i.p. with diisopropylfiuorophosphate were investigated. Pyridostigmine bromide (0.1 mg/kg) and atropine methylnitrate (20 mg/kg), which are centrally inactive, were pretreated i.m. 30 min and 10 min, respectively. before diisopropylfluorophosphate (10 mg /kg, $2LD_50$) poisoning to reduce the mortality and eliminate peripheral signs. Diisopropylfluorophosphate induced severe limbic seizures, and early necrotic and delayed apoptotic brain injuries. The necrotic brain injury, which was closely related to seizure intensity, was exerted as early as 1 hr predominently in hippocampus and piriform cortex. showing spongiform change (malacia) of neurophils in severe cases, in contrast to a typical apoptotic (TUNEL-positive)pattern after 12 hr in thalamus, and a mixed type in amygdala. Nitric oxide content in cerebrospinal fiuid significantly increased after 2 hr, reaching a maximal level at 6 hr. Pretreatment with $_L-N^G$-nitroarginine, an inhibitor of nitric oxide synthase, reduced nitric oxide content and attenuated only apoptotic brain injury in all four brain regions examined without affecting seizure intensity and necrotic injury. Taken together, early necrotic and delayed apoptotic brain injuries induced by diisopropylfiuorophosphate poisoning in rats may be related to seizure intensity and nitric oxide production, respectively.