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

The histochemical distribution of cholinesterases in the cerebral cortex and their response to cholinesterase inhibitors such as physostigmine and tetrahydroaminoacridine (THA) were investigated in brains from patients with Alzheimer's disease and control subjects. In the temporal neocortex of the control subjects, most of the cholinesterase activity was located within axons and cell bodies belonging to cholinergic pathways. In keeping with their well-known cholinomimetic effects, physostigmine and THA effectively inhibited this cholinesterase activity. Cholinesterase-containing normal axons (and in some cases cells) were severely depleted in the cerebral cortex of patients with Alzheimer's disease. Although the cerebral cortex of these patients continued to display abundant cholinesterase activity, the location of this enzyme was largely shifted to the neuritic plaques and neurofibrillary tangles. In fact, the majority of these pathological structures demonstrated intense acetylcholinesterase and butyrylcholinesterase activities. Physostigmine and THA were potent inhibitors of these plaque- and tangle-bound cholinesterases as well. In patients with Alzheimer's disease, cholinesterase inhibitors would therefore appear to have a major and widespread effect directly upon the enzymatic activity of plaques and tangles. Consequently, the clinical effects of anticholinesterases in Alzheimer's disease may be based on mechanisms that are different from those that apply to the normal brain.
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PMID:Anatomy of cholinesterase inhibition in Alzheimer's disease: effect of physostigmine and tetrahydroaminoacridine on plaques and tangles. 343 78

Cholinesterase activity and concentrations of total protein, albumin and globulins were measured in the serum of 94 carefully selected prematures and newborns during the first week of life. Cholinesterase activity was significantly lower in prematures than in newborns. There was a weak correlation between serum concentration of albumin and cholinesterase activity. Total protein, albumin and gamma-globulins were significantly lower in premature babies. With the exception of alpha-1-globulin, all proteins correlated positively with gestational age. There was no difference in total serum protein concentration between small for gestational age infants and appropriate for gestational age infants. Postnatally, serum protein and cholinesterase activity rose by 27 44% within 7 to 10 weeks in prematures of 30-33 weeks of gestational age. A single infusion of 0.5 g/kg b.w. albumin transiently increased the protein concentration of prematures 1.5 fold; 7 to 10 weeks later, protein concentrations of treated and untreated prematures were no longer different. In conclusion, cholinesterase activity and protein concentrations correlated with gestational age. In prematures with disturbed microcirculation, albumin infusions resulted in a transient increase of protein concentration.
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PMID:[Cholinesterase activity and protein concentration in the serum of premature and newborn infants]. 358 66

Cholinesterase inhibitors induce changes in plasma hormones in the rat. Since these compounds induce hypothermia the question has been raised as to whether the endocrine responses are secondary to the fall in core temperature. The time course of the changes in temperature and plasma levels of corticosterone, growth hormone and prolactin have been examined following injection of diisopropylphosphofluoridate (DFP), soman or physostigmine. All three cholinesterase inhibitors caused an initial rise in corticosterone; DFP decreased growth hormone; physostigmine reduced prolactin. The time course of the hypothermia after DFP and soman did not correlate with that of the rise in corticosterone. The data do not suggest that the hormone changes are secondary to the temperature change.
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PMID:Relationship between the temperature and endocrine changes induced by cholinesterase inhibitors. 358 58

Four hundred and thirty blood samples from suxamethonium-sensitive individuals have been phenotyped by the Cholinesterase Research Unit following its transfer from Exeter to the Hammersmith Hospital. The distribution of genotypes has been shown to be similar to that found in Exeter. Screening for the Elk and Elj genes has not yielded any major differences in the gene frequencies of sensitive individuals, even during pregnancy. The uneven sex distribution of the patients, as well as other unusual points that have arisen, are discussed. A new gene for the biosynthesis of cholinesterase has probably been identified.
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PMID:Phenotyping of individuals sensitive to suxamethonium. The Cholinesterase Research Unit at the Royal Postgraduate Medical School. 365 Dec 74

Male Sprague-Dawley rats were trained on a discriminated avoidance-escape task. They were administered subchronically saline, 12.7 micrograms/kg (0.125 LD50) soman, or 25.5 micrograms/kg (0.25 LD50) soman. Injections were given 5 days per week for 4 weeks. Injections were given subcutaneously immediately following the avoidance behavior test session. Soman produced a reduction in avoidance behavior efficiency in a dose dependent manner. When soman was discontinued, the rats recovered their pre-soman control baselines. Untrained rats given soman according to the same soman regimen were used to measure acetylcholine in brain and cholinesterase activities in brain, blood, and diaphragm. After 18 soman injections at 12.7 and 25.5 micrograms/kg acetylcholine was reduced significantly only in the amygdala. Blood cholinesterase was inhibited as much as 57% after 12.7 micrograms/kg soman and 74% after 25.5 micrograms/kg. Plasma cholinesterase was inhibited to 24% by the 12.7 micrograms/kg dose of soman and to 38% by the 25.5 micrograms/kg dose. Plasma cholinesterase recovered to control levels 11 days after cessation of soman, and whole blood cholinesterase recovered 25 days after cessation of the higher soman dose. Cholinesterase was inhibited significantly in the hippocampus and amygdala in a dose dependent manner. The cholinesterase activities appear to parallel the soman induced decrement in avoidance behavior and the subsequent recovery to control levels following withdrawal of soman.
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PMID:Effects of subchronic soman on avoidance-escape behavior and cholinesterase activities. 369 9

The acute toxicity of oxamyl, an insecticide and nematicide, has been evaluated to establish proper handling guides. The material is highly toxic when given as a single oral dose; its LD50 is in fasted rats 2.5 to 3.1 mg/kg, 2.3 to 3.3 mg/kg in fasted mice, and 7 mg/kg in guinea pigs. A beagle dog given 30 mg/kg died, while 15 mg/kg was not lethal. In all species, clinical signs of cholinesterase inhibition (lacrimation, salivation, tremors) were observed. Cholinesterase activity was depressed in rats treated with a single oral dose. Atropine, when given immediately after oxamyl, was antidotal. When given by intraperitoneal injection, oxamyl was highly toxic to rats, mice, and guinea pigs. The material is a mild eye irritant with the reaction limited to the conjunctiva and iris, but systemic absorption via eye contact makes use of protective equipment essential. Oxamyl produces mild skin irritation and the dermal absorption toxicity in rats (LD50 is greater than 1,200 mg/kg) and rabbits (740 mg/kg) is relatively high suggesting limited absorption. No sensitization was produced when tested in guinea pigs. Oxamyl is highly toxic via inhalation with the 1-hr LC50 value in rats being 0.17 mg/liter (male) and 0.12 mg/liter (female). The corresponding 4-hr value is 0.064 mg/liter for male rats which indicates that concentration X time is a constant through the time periods tested. Repeated-dose studies, orally in rats and dermally in rabbits, showed oxamyl to be noncumulative, with the target system being the nervous system mediated through cholinesterase inhibition. No specific tissue or organ pathology was seen in either species tested.
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PMID:Acute toxicity studies with oxamyl. 369 28

The effectiveness of physostigmine and atropine pretreatment against the lethal effects of sarin was studied in rats given lethal subcutaneous injections (130 micrograms/kg) of the organophosphate. Pretreatment of these animals with physostigmine 30 min prior to injection of sarin reduced mortality to 28% and when the drug coadministered with atropine only 4% of the animals died. The latter treatment also reduced significantly the extent and duration of symptoms due to sarin; however, atropine, pyridostigmine, and neostigmine injected alone did not protect animals against the lethal effects of sarin. Physostigmine caused only slight inhibition of cholinesterase in blood and skeletal muscle. Cholinesterase activity in blood and muscle of rats pretreated with physostigmine before sarin administration was significantly higher than in tissues from rats injected with sarin alone. In rats receiving sarin following pretreatment with physostigmine, twitch potentiation of extensor muscles and maintenance of tension during tetanic stimulation of the nerve recovered to near control levels. Muscle function recovered despite significant inhibition of cholinesterase. Effective protection against lethality by physostigmine could be related to protection of cerebral cholinesterase since inhibition of this enzyme by sarin was lowered significantly after pretreatment with physostigmine. Alternatively, physostigmine may also interact with the nicotinic acetylcholine receptor ion-channel complex directly.
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PMID:Effectiveness of physostigmine as a pretreatment drug for protection of rats from organophosphate poisoning. 369 40

Three organophosphate compounds, dichlorvos, parathion and diisopropylfluorophosphate were tested as an unconditioned stimulus in the conditioned taste aversion (CTA) test. All organophosphates caused a dose-dependent CTA in rats at doses which did not induce any other signs of toxicity. Experiments with dichlorvos showed that the minimum dose which caused CTA did not alter the rats' sensitivity to pain or their behavior in either an open field or an inclined plane. Cholinesterase activity was inhibited in a dose-dependent manner in brain and plasma after administration of the organophosphates and CTA was correlated with the degree of plasma cholinesterase inhibition. CTA appears to be a sensitive indicator of neurobehavioral effects of mild exposure to organophosphates which causes only 30-40% inhibition of plasma cholinesterase.
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PMID:Conditioned taste aversion induced by organophosphate compounds in rats. 370 7

Oxamyl (methylN',N'-dimethyl-N-[(methylcarbamoyl)oxy]-1-thiooxam imidate; CAS 23135-22-0) was tested for oral toxicity in the rat and dog (90-day and 2-year feeding studies) and in the mouse (2-year feeding study). Teratogenic potential was evaluated in the rat and rabbit and functional reproductive capacity was studied in the rat in a one- and a three-generation reproduction study. Rats fed a diet containing oxamyl at 500 ppm showed clinical signs of cholinesterase inhibition and body weight loss within 2 days. Feeding of either 100 or 150 ppm oxamyl for 90 days produced a reduced rate of weight gain without other signs of response, and no effects were detected at 50 ppm. An oxamyl feeding period of 2 years also showed depressed body weight gains in rats fed either 100 or 150 ppm. Cholinesterase activity was depressed only during the first week of feeding and only in the 150-ppm group. All other indices of response, including the type and distribution of tumors, were similar in the test and control rats and it was concluded that the no-observed-effect level was 50 ppm (equivalent to approximately 5 mg/kg). Mice fed oxamyl at 100 ppm for 6 weeks showed signs of cholinesterase inhibition and some mortalities, so the dietary concentration was reduced to 75 ppm in the 2-year study. Body weights of mice fed oxamyl at 50 or 75 ppm were lower than controls during the first 6 months of the study. No other signs of a toxic response to oxamyl were seen in mice and a no-observed-effect level of 25 ppm (approximately 2.5 mg/kg) was assigned to this compound. No evidence of a tumorigenic response was obtained. Dogs fed oxamyl at 150 ppm for 2 years showed marginal increases in serum alkaline phosphatase activity and cholesterol concentration but no tissue pathology was seen. No evidence of cholinesterase inhibition was seen. It was concluded that the no-observed-effect level for oxamyl in the dog was 100 ppm (approximately 2.5 mg/kg). In the one- and three-generation reproduction studies, litter sizes were somewhat lower in rats fed oxamyl at 100 or 150 ppm oxamyl with normal values seen at 50 ppm. Weanling body weights were normal in rats in the 50-ppm group for three generations but were reduced in the one-generation study. Pup body weights were lower in rats in both the 100- or 150-ppm groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic toxicity, reproductive, and teratogenic studies with oxamyl. 373 61

The relationship between physostigmine (Phy) concentration, acetylcholine (ACh), choline (Ch) and cholinesterase (ChE) activity was examined in whole rat brain after the administration of [3H]Phy (650 microgram/kg i.m.). Cholinesterase inhibition was found to be inversely related to Phy levels. Maximal inhibition (80%) was seen at 5 min and by 2 hrs ChE activity had returned to control levels. Acetylcholine levels in whole brain peaked at 30 min at a concentration (80 nmol/g) 2.3 times higher than controls (33 nmol/g). Choline levels were not significantly altered. The regional distribution of Phy concentration and ChE activity was studied in six areas of the brain following i.m. administration of three different dosages of ( 3H]Phy. Physostigmine concentration and ChE activity showed a dose dependency in each area examined except in SP (medial septum). Striatum (ST) showed the greatest relative increase of ACh up to 30 min, when compared to other areas. Choline levels were not changed in any area with the exception of ST at 5 min where a decrease was seen. There was a relationship between ChE activity, Phy concentration and ACh levels in all areas examined with exception of the medulla oblongata (MO). Our results indicate that even though ChE was inhibited practically uniformly in all brain areas, the percent increase with respect to control animals and the relative increase of ACh varied widely from area to area. This finding has clinical implications in cases in which cholinomimetic therapy is used to elevate ACh levels in specific brain areas which show a cholinergic deficit.
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PMID:Relation of brain regional physostigmine concentration to cholinesterase activity and acetylcholine and choline levels in rat. 374 73


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