• 대한임상독성학회지
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• 제5권1호
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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.

• Journal of Microbiology and Biotechnology
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• 제31권1호
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• pp.144-153
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• 2021

Organophosphorus nerve agents (OPNAs), including both G- and V-type nerve agents such as sarin, soman, tabun and VX, are extremely neurotoxic organophosphorus compounds. Catalytic bioscavengers capable of hydrolyzing OPNAs are under development because of the low protective effects and adverse side effects of chemical antidotes to OPNA poisoning. However, these bioscavengers have certain limitations for practical application, including low catalytic activity and narrow specificity. In this study, we generated a fusion-hybrid form of engineered recombinant human paraoxonase 1 (rePON1) and bacterial organophosphorus hydrolase (OPH), referred to as GV-hybrids, using a flexible linker to develop more promising catalytic bioscavengers against a broad range of OPNAs. These GV-hybrids were able to synergistically hydrolyze both G-type OPNA analogs (paraoxon: 1.7 ~ 193.7-fold, p-nitrophenyl diphenyl phosphate (PNPDPP): 2.3 ~ 33.0-fold and diisopropyl fluorophosphates (DFP): 1.4 ~ 22.8-fold) and V-type OPNA analogs (demeton-S-methyl (DSM): 1.9 ~ 34.6-fold and malathion: 1.1 ~ 4.2-fold above) better than their individual enzyme forms. Among the GV-hybrid clones, the GV7 clone showed remarkable improvements in the catalytic activity toward both G-type OPNA analogs (kcat/Km (106 M-1 min-1): 59.8 ± 0.06 (paraoxon), 5.2 ± 0.02 (PNPDPP) and 47.0 ± 6.0 (DFP)) and V-type OPNA analogs (kcat/Km (M-1 min-1): 504.3 ± 48.5 (DSM) and 1324.0 ± 47.5 (malathion)). In conclusion, we developed GV-hybrid forms of rePON1 and bacterial OPH mutants as effective and suitable catalytic bioscavengers to hydrolyze a broad range of OPNA analogs.

• 대한임상독성학회지
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• 제9권2호
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• pp.56-60
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• 2011

Purpose: The optimal dose of oximes for use in the treatment of organophosphorus pesticide poisoning has not been conclusively established. In this retrospective study, we assessed the effectiveness of the use of high-dose pralidoxime infusion in treating organophosphorus pesticide poisoning. Methods: From January 1998 to December 2009, 71 patients visited the hospital Emergency Department (ED) as a result of organophosphate pesticide intoxication. All of these patients received an initial bolus of 2 g of pralidoxime as the first step of treatment. Patients who then received continuous infusion of pralidoxime at a dose of 500 mg/hr were entered into study group 1 (low dose), and those treated by continuous infusion of pralidoxime at a dose of 1000 mg/hr were entered into study group 2 (high-dose). Plasma cholinesterase activities for each patient were evaluated at ED arrival and re-evaluated 24 hours after pralidoxime infusion. The effectiveness of the two treatment modalities was gauged by comparing the required duration of mechanical ventilation, time spent in the intensive care unit (ICU) and total time spent in the hospital. Results: The mean duration of mechanical ventilation was $9.98{\pm}6.47$ days for group 1 and $4.39{\pm}6.44$ days for group 2. The respective mean duration of time spent in ICU and the total number of days in the hospital were $16.38{\pm}18.84$ days and $21.87{\pm}20.16$ days for group 1, and $7.83{\pm}9.99$ days and $11.71{\pm}13.53$ days for group 2. Highdose pralidoxime treatment was associated with shorter required durations for mechanical ventilation, ICU and hospital stay. In addition, plasma cholinesterase reactivation rates were higher for those patients receiving high-dose pralidoxime treatment. Conclusion: The results suggest that high-dose pralidoxime treatment has greater efficacy for patients suffering from organophosphorus pesticide poisoning.

• Journal of Preventive Medicine and Public Health
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• 제23권2호
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• pp.194-200
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• 1990

The paraoxonase (E. C. 3.1.1.2) is a major enzyme to detoxicate the organophosphorus and carbamate which are the most widely used as the agricultural spraying insecticides. To investgate the distributions of plasma paraoxonase activity and the factors affecting the enzyme activity, the plasmas of 945 Korean rural population were analysed with the modified Krisch's direct sphectrphotometry method. Three indices of the enzyme activity - basal activity, stimulated activity (by NaCl), % stimulation - were obtained from the analysis. Three indicies suggested unimodal distributions, so we couldn't identify the low activity group risk group to organophosphorus & carbamate insecticides poisoning. There is no significant relation between 3 actvity indicies and sex, age, or history of insecticide use (p>0.05). The basal activity and the stimulated activity have significant relationship and high coefficient of determination with the activities of their parents ($r^2$=0.30, 0.24 ; p<0.05), but the % stimulation does not ($r^2$=0.02 ; p<0.05). These results suggest that the activity of paraoxonase is determined mainly by the genetic factor.

• 대한임상독성학회지
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• 제6권2호
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• pp.83-90
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• 2008

Organophosphate (OP) pesticides are the most common source of human toxicity globally, causing high mortality and morbidity despite the availability of atropine as a specific antidote and oximes to reactivate acetylcholinesterase. The primary toxicity mechanism is inhibition of acetylcholinesterase (AchE), resulting in accumulation of the neurotransmitter, acetylcholine, and abnormal stimulation of acetylcholine receptors. Thus, the symptoms (muscarinic, nicotinic, and central nervous system) result from cholinergic overactivity because of AchE inhibition. OP can also cause rhabdomyolysis, pancreatitis, parotitis, and hepatitis. OP therapy includes decontamination, supportive therapy, and the use of specific antidotes such as atropine and oximes. However, there has been a paucity of controlled trials in humans. Here we evaluated the literature for advances in therapeutic strategies for acute OP poisoning over the last 10 years.

• 한국군사과학기술학회지
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• 제16권2호
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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.

• Toxicological Research
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• 제17권4호
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• pp.287-296
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• 2001

The acute oral LD5O toxicity values of isazofos, pyraclofos, diazinon and methomyl were determined for Japanese quail based on OECD guideline. The $LD_{50}$ of isazofos, pyraclofos and diazinon was 16.26 mg/kg, and 7.11mg/kg body weight In female respectively. And the $LD_{50}$ of each chemical in male was 21.44, 35.64, 8.28 mg/kg body weight respectively. Diazinon was the most susceptible compounds to Japanese quail in both sexes. The $LD_{50}$ of methomyl was 21.24 mg/kg body weights in female, and 28.28 mg/kg body weight in male respectively. Diazinon, isazofos and methomyl were more toxic In the female than male. The symptoms of poisoning were similar in quails administrated with each chemicals. The clinical sign in Japanese quail were ataxia, salivation, diarrhea, ruffled feather and convulsion at dead point. There were severe hemorrhage and catarrhal inflammation from duodenum to ileum In all compounds. In Japanese quail treated with organophosphorus and carbamate compounds, brain acetylcholinesterase was inhibited by 88-96. The recovery was not observed after 5 h in sublethal dose.

• 약학회지
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• 제46권2호
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• pp.93-97
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• 2002

Methidathion is one of the organophosphorus pesticides commonly used for stamping out harmful pests in farming areas. This paper presents a fatality due to methidathion intoxication and describes the distribution of methidathion in postmortem blood and tissues obtained at autopsy. Qualitative identification of methidathion was achieved by TLC, GC and GC/MS, and quantitative analysis was performed by GC with thermionic specific detector (TSD). The analytes in postmortem specimens were extracted by liquid-liquid extraction (LLE) with ethylether. After the ethylether layer was evaporated, the residue was partitioned into hexane and acetonitrile, and the acetonitrile layer was used for analysis. Tissue specimens were homogenized with 4% perchloric acid and applied for LLE. After extraction, the extracts were reconstituted 100 $\mu\textrm{g}$ pyraclofos (IS, 100 $\mu\textrm{g}$/ml in methanol) for GC and GC/MS analysis. On analysis of postmortem specimens, methidathion was identified and quantitated. The methidathion concentrations were 2.0 $\mu$l/ml in blood, 24.4 $\mu\textrm{g}$/g in liver, 13.9 $\mu\textrm{g}$/g in lung, 21.8 $\mu\textrm{g}$/g in kidney, respectively.

• 대한임상독성학회지
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• 제9권2호
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• pp.61-70
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• 2011

Purpose: This study investigated the effect on survival rate for organophosphate intoxication patients who received trachostomy. This research was conducted to help identify appropriate treatment of patients who received a trachostomy. Methods: This research was retrospectively conducted using the medical records of 141 patients who arrived at the Chosun University Hospital emergency medical center between Jan 2007 and Dec 2010, suffering from organophosphate intoxication. They were placed in two groups including one which received trachostomy as part of their treatment and one that did not. The effect of each variable on mortality was evaluated by regressionanalysis. Results: Of 141 patients with organophosphate intoxication, 105 of them did not tracheostomy and 16 were dead cohorts (15.2%). Their size of pupil was 1mm. Factors such as amount of organophosphate ingested, PAM time after ingestion, average body temperature, arrival time, atropinization time after ingestion, AST/ALT, Bun/Cr all appeared to be significant factors in death cohorts (P<0.05). 36 patients among the total had tracheostomy and 11 ones of them were in dead cohort (30.6%) and their average age was 58 years. The facts affect the state of patients in dead cohort include the amount of intoxication which between $327.27{\pm}194.1ml$, performing intubation 686 mins after intubation, reaching to the hospital after 580mins, injecting PAM 744 mins after intoxication, injecting atropine 627 mins after intoxication. The largest cases of patient's state was found to be stupor with 14 patients (38.9%) the level of Cholinesterase in blood appeared to be significant in dead cohort as $391.00{\pm}353.9IU/L$ (P<0.05). Conclusion: Further planned studies are necessary on the use of tracheostomy for treatment of poisoning victims, especially those intoxicated by organophosphorus insecticides.

• 대한임상독성학회지
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• 제4권2호
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• pp.161-165
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• 2006

Organophosphate insecticides, commonly used in agriculture, are a gradually increasing cause of accidental and suicidal poisoning. Intoxication can occur by ingestion, inhalation or dermal contact. Exposure to organophosphorus agents causes a sequentially triphasic illness consisting of the cholinergic phase, the intermediate syndrome, and organophosphate-induced delayed polyneuropathy. Acute pancreatitis as a rare complication of organophosphate intoxication has also been infrequently observed. We report a case of intoxication with organophosphate (phos-phamidon) by parenteral exposure (inhalation and/or dermal contact). A 34-year-old male patient was transferred to our Emergency Medical Center and was intubated due to a progressive respiratory failure. He presented with meiotic pupils, cranial nerve palsies, weak respiration, and proximal limb motor weaknesses without sensory changes. He had been employed in filling syringes with phosphamidon during the previous month. Because the patient's history and symptoms suggested organophosphate intoxication with intermediate syndrome, he was mechanically ventilated for 18 days with continuous infusion of atropine and pralidoxime (total amounts of 159 mg and 216 g, respectively). During his admission, hyperamylasemia and hyperli-pasemia were detected, and his abdominal CT scan showed a finding compatible with acute pancreatitis. He was administered a conservative treatment with NPO and nasogastric drainage. The patient was discharged and showed neither gastrointestinal nor neurologic sequelae upon follow up at one week and three months.