Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methyl isocyanate (MIC) interaction with the rabbit erythrocyte membrane increased the fluidity of the membrane and decreased the osmotic fragility of erythrocytes both in vitro and in vivo in rabbits intoxicated with MIC subcutaneously. MIC inhibited both acetylcholinesterase (AChE) and adenosine triphosphatase (ATPase) activities of erythrocytes dose-dependently in vitro, while in vivo a decreased trend in ATPase activity with unaltered AChE activity was observed. MIC also caused significant decrease in plasma sodium level with corresponding increase in potassium level in rabbits. The observed effects are due to MIC, per se, as the hydrolysis products of MIC, methylamine and N,N'-dimethylurea did not affect the erythrocyte fluidity and enzymes activities both in vitro and in vivo while they increased the osmotic fragility of erythrocytes in vivo in rabbits administered subcutaneously in equimolar concentration to MIC dosage. Inhibition of Na(+)-K(+)-dependent ATPase with altered permeability to cations and also probably water transport of plasma membrane due to MIC interaction are envisaged.
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PMID:Acute toxicity of methyl isocyanate in rabbit: in vitro and in vivo effects on rabbit erythrocyte membrane. 153 91

Pyridostigmine bromide (Pyr), a reversible cholinesterase inhibitor, is currently suggested to be the most effective pretreatment drug against intoxication with potent organophosphates (OP). This investigation was conducted to determine if oral low doses of Pyr would affect performance of a simple visual discrimination task, and further to assess the alterations of motor or motivational function that might underlie the performance deficits in the water-deprived rats. Rats were trained extensively on a successive light-intensity discrimination implemented with the use of a multiple schedule. The multiple schedule consisted of one fixed-ratio (FR-10) and one differential reinforcement of low rates (DRL-10 s) component, which were signalled by the 10-s discriminative stimuli of bright (S+) and dim (S-) houselights, respectively, in simple alternation. The light intensity difference (S-/S+) was about 0.6. Pyr, at doses (3-12 mg/kg), which did not cause overt symptoms, moderately decreased S+ respondings but did not affect S- respondings. The ratio of S+/S- respondings, an index of discrimination performance, was moderately decreased. Over the range of doses evaluated, Pyr also attenuated the corresponding water intake in a dose-dependent manner, but it did not significantly affect locomotor activity. The lowest effective doses of the above affected behaviors were virtually identical (6 mg/kg). These results suggest that the disruptive effects of a single oral low dose of Pyr on the rat operant performance involve motivational dysfunction rather than motor impairment.
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PMID:Acute effects of oral low doses of pyridostigmine on simple visual discrimination and unconditioned consummatory acts in rats. 153 77

Thirty of 200 ewes died or were euthanatized during a 21-day period following a 1-day accidental exposure to natural gas condensate, a complex mixture of hydrocarbons obtained during collection of natural gas from wells. Despite access to potable well water, the poisoned ewes willingly consumed toxic doses of condensate that contaminated surface water. Eight animals died without premonitory signs; the remainder became ill over the course of a few days to 3 weeks. The principal cause of mortality was aspiration pneumonia, but myocardial degeneration and necrosis, renal tubular damage, gastritis, enteritis, and meningeal edema and hyperemia were also observed. Gas chromatographic analysis identified chemical traces of the hydrocarbons in the tissues, and "fingerprinting," the process of matching chromatographic tracings, provided forensic proof of the contamination source. Atomic absorption spectroscopy and cholinesterase analyses were performed to eliminate the possibility of toxicosis by heavy metal contaminants or other constituents. This appears to be the first reported incidence of natural gas condensate toxicity involving sheep or other ruminants. Although the available literature presents a suggestive pattern of clinical signs and pathologic lesions of petroleum product poisoning, diagnostic investigations should employ detailed analytic examination because each source of petroleum hydrocarbons contains unique sets of components that may produce different toxic effects.
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PMID:Toxicosis in sheep following ingestion of natural gas condensate. 155 62

A comparison of the bimolecular rate constants (ki) for inhibition of electric eel acetylcholinesterase (AChE) by the oxono (i.e., P=O) and thiono (i.e., P=S) analogues of parathion, methylparathion, leptophos, fonofos, sarin, and soman revealed that the oxono/thiono ratios of ki values varied from 14 for soman to 1240 for parathion. Analysis of the relative importance of the dissociation equilibrium constant and the phosphorylation rate constant in producing this variation in ki values indicated that the oxono analogues and the phosphorylation rate constant values that varied in a narrow range from 8- to 14-fold greater than their thiono counterparts, while the oxono/thiono ratios for dissociation constants varied widely from 1 for soman to 82 for fonofos. The lower affinities of thiono analogues for AChE probably resulted from differences in the hydrophobic binding of oxono and thiono analogues to the active site of AChE, inasmuch as the hydrophobicities (i.e., octanol/water partition coefficients) of thiono organophosphorus compounds were much greater than the hydrophobicities of their oxono analogues. Quantitative structure--activity analysis indicated that the hydrophobic effects of oxono and thiono moieties correlated with log ki for AChE inhibition to a greater extent (r2 = 0.79) than their electronic effects (r2 less than or equal to 0.48). These observations suggest that the differences in hydrophobicity of oxono and thiono analogues of organophosphorus compounds may be as important as their electronic differences in determining their effectiveness as AChE inhibitors.
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PMID:Quantitative structure-activity analysis of acetylcholinesterase inhibition by oxono and thiono analogues of organophosphorus compounds. 158 39

Embryonic cerebral tissues (ECT) either fresh or frozen-stored, were cultured and transplanted into the cerebella of neonatal host rats. Many variables including composition of the freezing medium, freezing and thawing rates, and storage time in liquid nitrogen were studied systematically. The results indicated that the following conditions yielded good results for tissue culture: using 1 M Me2SO as the cryoprotectant, freezing the brain tissues at a rate of 1 degrees C/min until it reached -70 degrees C, storing the frozen samples in liquid nitrogen and thawing them fast in a 37 degrees C water bath. The viability of the frozen-thawed tissues was assessed by their abilities to grow and differentiate in vitro and in vivo after intracerebral grafting. In tissue culture, growth and differentiation were similar to those of the fresh ECT. Cell morphology and staining reactions were normal in supravital methylene blue staining, cresyl violet staining, and acetylcholinesterase staining. Neurons had well-developed Nissl bodies, and cholinergic neurons also differentiated. Autoradiographic studies showed that more than 50% of the neurons had the ability to uptake gamma-aminobutyric acid with high affinity. In brain tissue transplantation, 9 of 12 transplants survived subsequent grafting after cryopreservation. Moreover, the grafts of surviving cryopreserved tissue displayed cytological and cytoarchitectural characteristics identical to those of fresh grafts. All grafts were integrated with the surrounding host neural tissue. This suggested that there may be synaptic connections between the transplants and the host brain tissues. From this and similar studies on the subject by others wer conclude that cryopreservation is a feasible method for storage of embryonic brain tissue to be used later for intracerebral grafting.
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PMID:Cryopreservation of embryonic cerebral tissue of rat. 158 33

A flow injection system, incorporating an acetylcholinesterase (AChE) single bead string reactor (SBSR), for the determination of some organophosphorous (azinphos-ethyl, azinphos-methyl, bromophos-methyl, dichlorovos, fenitrothion, malathion, paraoxon, parathion-ethyl and parathion-methyl) and carbamate insecticides (carbofuran and carbaryl) is presented. The detector is a simple pH electrode with a wall-jet entry. Variations in enzyme activity due to inhibition are measured from pH changes when the substrate (acetylcholine) is injected before and after the passage of the solution containing the insecticide. The percentage inhibition of enzyme activity is correlated to the insecticide concentration. Several parameters influencing the performance of the system are studied and discussed. The detection limits of the insecticides ranged from 0.5 to 275 ppb. The determination of these compounds was conducted in Hepes buffer and a synthetic sea water preparation. The enzyme reactor can be regenerated after inhibition with a dilute solution of 2-PAM and be reused for analysis. The immobilized enzyme did not lose any activity up to 12 weeks when stored at 4 degrees C.
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PMID:Determination of organophosphorous and carbamate insecticides by flow injection analysis. 159 94

Nine fairways of a golf course located in Bellingham, Washington were treated with diazinon AG500 at a target application rate of 2.2 kg active ingredient (AI) per ha. The chemical application with a "boomless" sprayer resulted in a variable distribution of diazinon residues on the turf (associated with a deep thatch layer) that ranged from 1.0 to 6.2 kg AI/ha. The diazinon-treated turf was irrigated with 1.3 cm of water immediately following application. The post-irrigation diazinon residue levels ranged from 100 to 333 ppm (mean = 209; SD = 88; n = 8). These residue levels were higher than expected based on results of turf studies in other regions of the United States. Eighty-five American wigeon (Anas americana) died after grazing on one treated fairway on the day of application following irrigation. The brains of all 85 wigeon were analyzed for acetylcholinesterase (AChE) activity. Wigeon that died on the study area (n = 85) showed 44% to 87% depression of AChE (mean = 76%; SD = 7.1%) when compared to control wigeon (n = 3; AChE Activity = 1.86) AChE levels. Upper GI tract contents of 15 of the 85 dead wigeon contained 0.96 to 18.1 ppm diazinon. Extensive carcass searches revealed no other avian mortality attributable to diazinon toxicity on the treated study area. Although initial post-irrigation diazinon residues in grass samples were higher than expected, diazinon levels in grass samples on day seven post-application had declined to an average of 29 ppm. American wigeon appear to be vulnerable to exposure to diazinon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:American wigeon mortality associated with turf application of diazinon AG500. 160 78

Looking for a possible protective effect of heavy water on proteins, cholinesterase and lactate dehydrogenase in combination with D2O and further protective substances were exposed to a temperature of 60 degrees C (for 10 min) and about 45 degrees C (for several days). In combination with glycerine there resulted an additive protective effect; with NaCl and/or albumin being added the individual effects raised to a higher level. In the cold D2O protects cholinesterase only against acid denaturation, but in combination with warmth also against basic denaturation.
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PMID:[Heavy water (D2O) as a protective protein containing medium. Example: human cholinesterase]. 166 Nov 14

Chronic alcohol (20% v/v in drinking water for 28 weeks) impaired acquisition of radial maze spatial and associative tasks by increasing both within-trial working and long-term reference memory errors; animals with high (above the median of 100 mg/100 ml) blood alcohol concentrations (BACs) during treatment were significantly more impaired than those with BACs below the median. Alcohol-treated rats showed improvements in radial maze performance after treatment with cholinergic agonists (arecoline and nicotine) and disruption with antagonists (scopolamine and mecamylamine) at low doses which did not affect controls. These effects were more pronounced for working than reference memory, and not manifest with the peripherally acting antagonists hexamethonium and N-methylscopolamine. Transplants into cortex and hippocampus of cholinergic-rich basal forebrain (BF) and ventral mesencephalon (VM) foetal neural tissue improved radial maze performance of alcohol-treated rats to control level over a period of 9-12 weeks after grafting. Cholinergic-poor foetal hippocampal (HC) grafts were without effect. BF and VM, but not HC, grafts showed dense acetylcholinesterase (AChE) staining, tyrosine-hydroxylase staining was most pronounced in VM sections and dopamine-beta-hydroxylase staining was minimal in all grafts. Choline acetyltransferase (ChAT) activity was significantly reduced in cortex and hippocampus of alcohol-treated rats, except those given cholinergic-rich transplants. Alcohol treatment also significantly reduced AChE-positive cell counts in the nucleus basalis, medial septal and diagonal band brain areas, at the sources of the forebrain cholinergic projection system (FCPS). Cortical levels of noradrenaline were significantly reduced in all alcohol-treated rats, regardless of transplant, whereas cortical dopamine content was significantly elevated in all rats receiving transplants, regardless of behavioural effect, but not in alcohol-treated controls. Forebrain serotonin levels were not significantly altered by grafting or alcohol treatment. These results suggest that damage to the FCPS, as shown by reduced ChAT activity in target areas, and reduced AChE cell counts in projection areas, played an important part in the radial maze deficits displayed by alcohol-treated rats, since these animals were sensitive to cholinergic drug challenge, and cholinergic-rich transplants from two different sites in foetal brain elevated ChAT activity and restored cognitive function. In contrast alcohol- or graft-induced alterations in other transmitter systems did not correlate with the pattern of behavioural deficit and recovery.
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PMID:The effects of cholinergic drugs and cholinergic-rich foetal neural transplants on alcohol-induced deficits in radial maze performance in rats. 167 82

Synaptosomes isolated from calf brain cortex were lysed and fragmented by Yeda press treatment. The obtained membranes have previously been fractionated in a counter-current distribution process using a liquid-liquid two-phase system consisting of water, dextran, Ficoll and poly(ethylene glycol) [J. Chromatogr., 358 (1986) 147]. Using the fact that there are discrete membrane populations, a rapid preparative method for isolation of the two main fractions is presented in the present work, as well as a subfractionation of one of them using liquid-liquid extraction with dextran-bound Procion yellow HE-3G. The content of several membrane constituents, i.e. protein, acetylcholinesterase, succinate dehydrogenase and ATPase, as well as opiate binding, were determined for the three fractions. Counter-current distribution of the fractions elucidates their heterogeneity and the effectiveness of the purification.
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PMID:Subfractions of membranes from calf brain synaptosomes obtained and studied by liquid-liquid partitioning. 171 38


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