Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human volunteers, studies to assess the adverse effects of the carbamate anticholinesterase physostigmine showed that the intramuscular dose observed to induce emesis in 50% of subjects tested (ED50) was 28.1 (23.5-120.7) micrograms/kg. This dose reduced whole blood cholinesterase (ChE) activity to 60% of control values. Studies in marmosets to assess the behavioural toxicology of physostigmine showed that the corresponding ED50 and ChE activity values were 34.3 (21.5-55.8) micrograms/kg and 66% respectively. Sarin was also shown to induce emesis in marmosets, but only at doses that reduced erythrocyte ChE activity to 12% of control values. These data seem also to correspond with reports of organophosphate poisoning in humans. It is concluded that the marmoset may be a very good model of both carbamate and organophosphate-induced emesis in humans.
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PMID:A model for carbamate and organophosphate-induced emesis in humans. 190 98

The effect of Soman, Sarin and Vx, known potent cholinesterase inhibitors, on the binding of several neurotransmitter receptors in various regions of brain was studied. Vx, exhibited considerable inhibition of binding of 3H-N-methylscopolamine (3H-NMS) to muscarinic receptors and of 3H-spiperone to dopamine D2 receptors in the striatum. 3H-NMS binding was 50% inhibited at 10(-6)M and 90% at 10(-3)M Vx. Inhibition of 3H-spiperone binding by Vx in striatum had an ID50 of 10(-5)M. KD of the treatment was affected more than Bmax. Binding inhibition of both 3H-NMS and 3H-spiperone in post-mortem brain of rats pre-treated with Vx confirmed the specificity of the organophosphates effect, since other organophosphates and ligands failed to show any activity.
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PMID:Effect of organophosphates on dopamine and muscarinic receptor binding in rat brain. 214 Dec 56

To estimate the potential of small doses of sarin (types I and II) and soman to cause delayed neuropathic effects, 400, 200, 61, and 0 micrograms/kg of sarin-I, 280, 140, 70, and 0 micrograms/kg of sarin-II, and 14.2, 7.1, 3.5, and 0 micrograms/kg of soman by gavage were compared with 510 mg/kg tri-o-cresyl phosphate (TOCP) in 14- to 18-month-old SPF white leghorn hens (4/dose) protected with atropine (100 mg/kg). The neuropathy target esterase (NTE) activity 24 hr after dosing was determined in brain, spinal cord, and lymphocytes and in plasma and brain for cholinesterase and carboxylesterase. None of the compounds showed statistically significant NTE decreases. Sarin-II showed a dose-related trend in the lymphocyte NTE (to 33% of control at 280 micrograms/kg), suggesting that longer exposure to lower doses might cause a cumulative neurotoxic insult. All of the agents decreased the activity of plasma and brain cholinesterase and carboxylesterase. Using more than 70% inhibition of brain NTE as a biochemical predictor of delayed neuropathy, sarin and soman appear unable to cause delayed neuropathy at nonlethal doses within this protocol.
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PMID:Neuropathy target esterase in hens after sarin and soman. 276 93

Sarin, a highly toxic cholinesterase (ChE) inhibitor, administered at near 1 LD50 dose causes severe signs of toxic cholinergic hyperactivity in both the peripheral and central nervous systems (CNS). The present study evaluated acute and long-term neuropathology following exposure to a single LD50 dose of sarin and compared it to lesions caused by equipotent doses of soman described previously. Rats surviving 1 LD50 dose of sarin (95 micrograms/kg; IM), were sacrificed at different time intervals post exposure (4 h-90 days) and their brains were taken for histological and morphometric study. Lesions of varying degrees of severity were found in about 70% of the animals, mainly in the hippocampus, piriform cortex, and thalamus. The damage was exacerbated with time and at three months post exposure, it extended to regions which were not initially affected. Morphometric analysis revealed a significant decline in the area of CA1 and CA3 hippocampal cells as well as in the number of CA1 cells. The neuropathological findings, although generally similar to those described following 1 LD50 soman, differed in some features, unique to each compound, for example, frontal cortex damage was specific to soman poisoning. It is concluded that sarin has a potent acute and long-term central neurotoxicity, which must be considered in the design of therapeutic regimes.
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PMID:Sarin-induced neuropathology in rats. 777 55

Diisopropyl methylphosphonate (DIMP), produced during manufacture of the chemical agent GB (Sarin), is a groundwater contaminant at Rocky Mountain Arsenal, Colorado. DIMP was fed for 90 days to dark brown "Ranch Wild" mink housed under controlled indoor conditions. One-year-old mink, 10 of each sex, were fed 0, 50, 450, 2700, 5400, or 8000 ppm in standard ranch diet. Actual DIMP consumption was 0, 8, 73, 400, 827, and 1136 mg/kg body wt/day, respectively. Two additional groups of 10 served as "pair-fed" controls. Body weight and food intake were recorded weekly. Complete blood count and 15 chemical analytes were measured at Weeks 0, 3, 7, and 13. Necropsy and microscopic examination were performed on all mink. No clinical morbidity or deaths occurred. Both sexes fed 8000 ppm ate approximately 20% less and weighed approximately 20% less than the controls; 5400 ppm females had a 10% weight decrement. Plasma cholinesterase (ChE) decreased in the top three dose groups starting at Week 3. At 13 weeks, decrements were approximately 50% but returned to normal after 1 week without DIMP. Erythrocyte ChE was not reduced. Heinz bodies occurred in 10-15% of RBCs in 50% of 8000 ppm mink at 13 weeks, and 0.1-2.0% of RBCs in 25% at 2700 ppm. There were mild decreases in RBC count, hematocrit, and hemoglobin, and increases in reticulocyte count, at the 5400 and 8000 ppm doses. All recovered within 3 weeks after DIMP was withdrawn. The 8000 ppm group had marginal splenic hematopoiesis, histologically. No other treatment-related changes were noted. The 450 ppm dose was a clear no-effect level (approximately 73 mg DIMP/kg body wt/day). Compared to reports of similar studies of DIMP in rats and dogs, these mink displayed no unique species susceptibility.
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PMID:Subchronic oral toxicity study of diisopropyl methylphosphonate in mink. 800 74

An enzyme test has been worked out for detecting organophosphorus compounds in water. The test is based on the inhibition of cholinesterase. The detection limits for the "nerve gases" are (microgram/L): Soman 0.12, VX 5.9, Sarin 9.9 and Tabun 26. The detection limit for the organophosphorus pesticide dichlorvos is 50 micrograms/L.
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PMID:A field-test for detecting organophosphorus compounds in water. 824 25

Sarin (Agent GB, isopropyl methylphosphonofluoridate) is an organophosphate cholinesterase inhibitor. Sarin (Type I or Type II) was administered by gavage to CD rats on d 6-15 of gestation at dose levels of 0, 100, 240, or 380 micrograms/kg/d and to New Zealand White (NZW) rabbits on d 6-19 of gestation at dose levels of 0, 5, 10, or 15 micrograms/kg/d. Females were weighed on gestational days (GD) 0, 6-16 for rats and 6-20 for rabbits, and immediately prior to termination (GD 20 for rats and GD 29 for rabbits). All animals were monitored daily for clinical signs of toxicity throughout dosing and until sacrifice. At necropsy, gravid uteri were weighed and examined for the number and status of implants (live, resorbed, or dead). Individual fetal body weight, malformations, and variations (external, visceral, and skeletal) were recorded. Rat and rabbit dams in the high-dose groups exhibited significant signs of maternal toxicity and increased maternal mortality. Examination of gravid uteri revealed no statistical differences among treatment groups in the incidence of resorptions or of dead or malformed fetuses, or in average body weight of live fetuses per litter. These results show no evidence or developmental toxicity in the CD rat or NZW rabbit following exposure to either Type I or Type II sarin during embryonic differentiation and major organogenesis, even at a dose that produced maternal toxicity.
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PMID:Developmental toxicity of sarin in rats and rabbits. 860 49

A patient severely poisoned with sarin in the Sarin Attack in Matsumoto is described. A 19-year-old man was exposed to sarin at 23:00 on 27 June, 1994. At 1:00 of the following day, a rescue team found and brought him to the hospital. His blood pressure was 150-80mmHg and the heart rate was 120/min with frequent premature ventricular contractions (PVC). His respiration was shallow and copious salivation and excretion from the respiratory tract were observed. Consciousness disturbance, generalized convulsion, severe miosis and fasciculation of tongue, facial muscle and extremities were also marked. Serum cholinesterase was 21 U/l (normal 109-249) and acetylcholinesterase in erythrocyte (E-AchE) was 0.1U/l (normal 1.2-2.0). Electroencephalogram (EEG) 30 hours after exposure showed polispike and wave complexes. Ventilatory assistance, forced urination and injection of diazepam and atropin improved his general condition and he was discharged 18 days after exposure. Three months after exposure, E-AchE was normalized and there was no complaint. But one year after exposure, EEG showed epilecpic discharges during sleep, and Holter electrocardiogram showed frequent PVC. As no clinical cases of severe sarin poisoning like this patient was reported, a longterm follow-up of this patient is very important.
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PMID:[A case of severe sarin poisoning in the sarin attack in Matsumoto--one-year follow-up of clinical findings, and laboratory data]. 872 Mar 36

Since plasma is generally employed for amino acid analysis, we compared amino acid levels in plasma with those in serum for healthy individuals and examined the influence of separation and storage conditions on the stability of the samples. Then, we determined the amino acid levels of frozen serum samples obtained from sarin poisoned patients. A. Comparison of Amino Acid Levels in Plasma and Those in Serum Blood was collected from 5 healthy individuals. Then, heparinated plasma and serum were separated by centrifugation immediately after blood collection. Serum was also separated by centrifugation after standing whole blood at room temperature for 1 hour. Frozen plasma and serum were store at -40 degrees C for 5 months. All were subjected to analysis in an amino acid analyzer. It was found that the cystine (Cys) and 3-methyl-histidine (3-M-His) levels in serum and plasma were affected when stored in a frozen state, that the aspartate (Asp) level was changed according to the method of collecting serum, and that the taurine (Tau) and ornithine (Orn) levels were affected by standing blood. B. Analysis of Blood Taken from Sarin Poisoned Patients Twelve sarin poisoned patients were selected as subjects, and serum cholinesterase (Ch-E) and serum albumin (Alb) levels were determined. Amino acid analysis was conducted using an amino acid analyzer. Serum samples which had been obtained from the 6 patients and frozen and stored at -40 degrees C from 5 months were used for amino acid analysis. As a result, the serum Ch-E level decreased and the Alb level tended to rise. Since the Ch-E/Alb ratio was reduced in the sarin poisoned patients, it is considered useful for discrimination from liver cirrhosis in which both Ch-E and Alb levels decreased. Amino acid levels in the serum obtained from the sarin poisoned patients were compared with those of healthy individuals, both of which had been stored under the same conditions. There were significant differences in Asp, glutamate (Glu), phenylalanine (Phe), 3-M-His, glutamine (Gln), and Cys levels. The Glu, Phe, and Gln levels were not affected by storage of serum in a frozen state, while the Glu and Phe levels were elevated and the Gln level was reduced. Although Cys exhibited lower values in frozen serum samples, the Cys level was elevated with a rise in the serum Ch-E levels. Therefore, we deduced that Cys metabolism disorders also occur in sarin poisoning. As stated above, the Glu and Phe levels were elevated and the Gln and Cys levels were reduced, suggesting the presence of abnormal amino acid metabolism, in patients with sarin-poisoning.
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PMID:[Blood amino acid levels in sarin poisoning patients]. 928 31

To evaluate delayed (long-term) effects of acute sarin poisoning on postural balance, nine male and nine female victims of the Tokyo Subway Sarin Poisoning in Japan (sarin cases) were examined by computerized posturography 6-8 months after the poisoning. Their plasma cholinesterase activities (ChE) on the day of the poisoning (March 20, 1995) were 13-95 (mean 68.2) IU/l for females and 19-131 (mean 75.9) IU/l for males, which were not significantly different between the two sexes. In females, the postural sway of low frequency (0-1 Hz) in the anterior-posterior direction and area of sway with eyes open was significantly larger in the cases than in the controls. Romberg quotients for the low-frequency sway in the anterior-posterior direction for females and low-frequency sway and length of sway in the medio-lateral direction for males were significantly related to log ChE. It is suggested that a delayed effect on the vestibulo-cerebellar system was induced by acute sarin poisoning; females might be more sensitive than males.
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PMID:A preliminary study on delayed vestibulo-cerebellar effects of Tokyo Subway Sarin Poisoning in relation to gender difference: frequency analysis of postural sway. 946 16


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