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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholinesterase (ChE) levels (Ellman method) were monitored in 90 subjects (69 males and 21 females) exposed to carbamate and organophosphate pesticides (78 agricultural workers and 12 pesticide vendors). Pre-exposure baseline values of plasma and red blood cell cholinesterase activities were defined for each subject with two blood samples (23 workers) or three blood samples (59 workers) taken almost thirty days after the last exposure. After control of intra-individual variation, 8 subjects with only one pre-exposure value and 13 with a coefficient of variation above 30% were excluded. For the other 59 subjects, the intra-individual variation of erythrocyte ChE (16%) was similar to the inter-individual one (15%), whereas the inter-individual variation of plasma ChE (21%) was higher than the intra-individual one (14%). Laboratory variation for plasma ChE measurements was 8%. Baseline values were analyzed (ANOVA) for sex, age, task and hour and season of sampling. Both erythrocyte and plasma enzymes, corrected for hematocrit, were lower in females. Plasma cholinesterase activity was lower in "re-entry" agricultural workers and in pesticide vendors. Post-exposure cholinesterase activity was measured in 54 workers within a few (1-21) days after last handling. Average relative reduction was 15.2% (95% C.I. = 4.9%-25.5%) in erythrocyte cholinesterase activity and 29.1% (95% C.I. = 18.2%-40.1%) in plasma cholinesterase activity. The one-way variance analysis showed marked plasma ChE reduction in mixers, loaders and appliers (36%, 95% C.I. = 24%-48%) and in parathion handlers (35%, 95% C.I. = 21%-49%. No significant reduction in blood cell cholinesterase activity in relation to task and to pesticide handled was observed. We conclude that the intra-individual variations of the baseline values were higher for three repetitions (88% and 84% of the population were within a variability of less than 30%, for AChE and for ChE respectively) than for two repetitions (91% and 88% of the population were within 30% of variability for AChE and for ChE respectively). The figures show a greater sensitivity of plasma ChE activity in acute exposure, probably due to a poor reliability in detection of erythrocyte ChE by local laboratories. The maximum reduction (38%, 95% C.I. = 22%-53%) in plasma ChE activity was observed within six days of the last exposure in loaders and appliers.
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PMID:[The monitoring of cholinesterases in farm workers and tradesmen exposed to phosphoric esters and carbamates]. 163 Apr 2

The recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor sites (MAChRs) following a reduction due to a repeated treatment (2 weeks) with the antiChE agent, isofluorophate (diisopropyl fluorophosphate, DFP) was studied in young (3 months) and aged (24 months) male Sprague-Dawley rats. At the end of DFP treatment the inhibition of ChE in the cerebral cortex, hippocampus and striatum did not differ between young and aged rats (about 70%); the down-regulation of MAChRs (without changes in affinity) varied from 20 to 40% for various areas of brains of rats belonging to the two age-groups, and was the most pronounced in the cerebral cortex of aged rats. As assessed by factorial analysis of variance (2 ages x 2 recoveries ANOVA) there were age-related differences in the recovery rate of both ChE and MAChRs during 5 weeks from the end of DFP treatment. The impairment of recovery observed in aged rats was present in three brain areas and was the most pronounced in the cerebral cortex. Choline acetyltransferase (ChAT) was not influenced by the age and/or treatment in the cerebral cortex and hippocampus while in the striatum an age-related decline was observed. The overall data appear of interest in relation to the recent use of antiChE organophosphorus compounds in the therapy of age-related memory disorders.
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PMID:Age-related differences in the recovery rate of brain cholinesterases, choline acetyltransferase and muscarinic acetylcholine receptor sites after a subacute intoxication of rats with the anticholinesterase agent, isofluorophate. 213 Jun 46

Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP (doses in mg/kg: first 1.1, two of 0.7 and four of 0.35) on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there was a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration (for many hours after each injection), in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment (about 70%) did not differ between young and surviving aged rats. The down-regulation of mAChRs (without changes in affinity) was present in the three brain regions of both young and aged rats (from 20 to 40%). Factorial analysis of variance (2 ages x 2 recoveries ANOVA) showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in the three brain areas. For example, cortical ChE in young rats reached pretreatment levels within 3 weeks, while hippocampal and striatal ChE activity recovered within 4 weeks; at these intervals ChE activity in aged rats was still considerably reduced (except in the striatum). Cortical and striatal mAChRs in young rats almost normalized within 1 week and hippocampal mAChR binding sites normalized within 2 weeks; at these intervals Bmax in aged rats were markedly below control levels. The overall data indicate that the recovery rate to normal baseline levels of ChE activity and mAChRs, following the termination of repeated treatment with the antiChE agent, is impaired in brain of aged rats. The delay in recovery rate is particularly evident in the cerebral cortex.
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PMID:Impaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats. 232 3

To establish the dose dependency of phospholipase A2 (PLA2) inhibition by the organophosphorus compound (OPC) paraoxon (POX), human platelet membranes were incubated after Ca2+ removal (to inactivate the PLA2) with 0.3, 1 and 3 microg ml(-1) POX for 5, 30 and 60 min each. The PLA2 activity (pmol mg[-1] protein min[-1]) was measured after subsequent enzyme reactivation. The PLA2 activity in native platelets was considered to be 100%; all other measured values are expressed as a percentage thereof. Data were analysed with the Mann-Whitney Wilcoxon rank order test and ANOVA. Statistical significance was assumed for P < or = 0.01. Paraoxon inhibited in a dose-dependent manner the PLA2 activity. Different incubation times of the inactive PLA2 with POX did not have any additional effect on the activity reduction after activation. At the tested POX concentrations the PLA2 activity was 42 +/- 5.4%, 29 +/- 3.4% and 15 +/- 6.6%, respectively. The corresponding butyrylcholine esterase (BChE) activities were <<1% of the baseline activity. Phospholipase A2 is less sensitive to POX inhibition than BChE and, at clinically achievable POX concentrations, shows a clear dose dependency. Further work is needed to elucidate the exact mechanism and time dependency of the phenomenon.
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PMID:Dose-dependent inhibition of phospholipase A2 by paraoxon in vitro: preliminary results. 941 52

In this study, the mouse was used to evaluate paternal germline exposure to the organophosphate methamidophos for its potential to produce adverse effects on spermatozoa and in the offspring. There have been reports that organophosphate exposure can increase abnormal sperm morphology in mice. However, effects transmitted to the offspring following paternal exposure have not been reported previously. The maximum tolerated dose (MTD) was 7.5 mg kg(-1) body weight and this dose resulted in no deaths, although blood plasma cholinesterase activity was still decreased. Males were euthanized 4 weeks after an acute intraperitoneal injection of methamidophos (0.5, 3.75, 5.0, and 7.5 mg kg(-1) body wt) and the number of spermatids per gram testes and sperm morphology were analyzed. In this study, abnormal sperm morphology on a per group basis exhibited a dose-response significantly related to increased methamidophos exposure as indicated by regression analysis and a nested ANOVA (p < 0.0001). Preimplantation embryos that were conceived 6 weeks after paternal methamidophos exposure (5 mg kg(-1) body wt) exhibited a significant increase in cleavage arrest. Fertility of males was also affected as shown by a decrease in the number of two- to four-cell embryos per male (postexposure week 6) and an increase in the number of degenerated embryos (postexposure weeks 4-6). We conclude that methamidophos may have the potential to produce transmissible adverse embryonic effects following an acute paternal germline exposure.
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PMID:Paternal effects from methamidophos administration in mice. 1082 10

Freshwater clams Corbicula fluminea were exposed in aquariums to four doses of trichloroethylene-TCE-(1.56 up to 100 mg/1) or toluene-TOL-(7.5 up to 60 mg/1) for 5 days. At the end of exposure, components of (de)toxification metabolism of phases I and II, parameters related to oxidative stress and propionylcholinesterase activity were assayed. Determination of TCE and TOL concentrations in water revealed an important evaporative loss during the experiment, characteristic of acute and occasional contaminations by such products occurring in the environment. Appropriate statistical methods such as ANOVA, Tukey test and discriminant analysis underlined the relevance of cytochromes P450 and P418, NADH-cytochrome c reductase, catalase, peroxided and peroxidizable lipids and net peroxidation as biomarkers of exposure to these solvents in C. fluminea. This experiment emphasised the importance of a multi-biomarker approach in environmental surveys and will be completed further by mesocosm studies.
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PMID:Potential biomarkers of trichloroethylene and toluene exposure in Corbicula fluminea. 1116 53

The EQM Research, Inc., portable test kit was evaluated as a surveillance tool for blood cholinesterase levels among migrant workers and their children. Laboratory validation demonstrated a linear relationship between the reference Ellman and kit methods (Ellman = 0.95 x kit result + 0.82, r2 = 0.98). Pre- and post-season cholinesterase levels measured in 70 farm workers were within normal ranges, but significantly different at 28.5 and 29.7 U/g Hb, respectively (paired t-test, p = 0.014). Results from 98 migrant farm worker children and a comparison group of 53 age-matched non-agricultural children showed that cholinesterase levels were not significantly different between the agricultural and non-agricultural children (ANOVA, p = 0.69). These data demonstrate that a portable test kit can provide useful data pesticide exposures when measurements are made in a temperature-controlled setting.
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PMID:Monitoring acetylcholinesterase levels in migrant agricultural workers and their children using a portable test kit. 1139 1

Patients suffering from Parkinson's disease (PD), often develop dementia (PDD). Their brain histology reveals Alzheimer's disease (AD) like changes and decreased cholin-acetyl transferase (ChAT) activity, in addition to typical PD changes. This cholinergic deficiency has been related to the degree of mental decline. As centrally acting cholinesterase inhibitors (ChEIs) provide cognitive and non-cognitive improvement for AD patients, the same therapeutic effect was hypothesized for PDD patients as well. The goal of this study was to assess the effect of ChEIs on both the cognitive and motor state of PDD patients. An open study was conducted. Eleven consecutive PDD patients (M/F 6/5 mean age 75 y) were found eligible for inclusion. They were treated for 26 weeks with tacrine (7 patients) and donepezil (4 patients) as add-on to their regular anti PD drugs. Cognitive assessment was performed at baseline and endpoint by Mini-Mental-State-Examination (MMSE) and Alzheimer's-Disease-Assessment-Scale (ADAS-cog). Global Deterioration Scale (GDS) was performed to evaluate active daily living (ADL). Motor evaluation was performed using Short Parkinson Evaluation Scale (SPES) at baseline and end-point. Statistical analysis used Student's paired t-test, ANOVA with repeated measures and Pearson correlation coefficient. ChEIs treated PDD patients showed improvement in their cognitive state. Mean ADAS-cog improved significantly by 3.2 points (p < 0.012). Mean MMSE and GDS improved non-significantly by 1.2 and 0.2 points respectively. There was no change in motor function as evident by mean SPES scores, 16.5 at baseline and endpoint. Five individuals actually demonstrated motor improvement under ChEIs. We conclude that ChEIs have a beneficial effect on the cognitive state of PDD patients without aggravating motor function.
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PMID:The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson's disease and dementia. 1176 30

Centrally acting cholinesterase inhibitors (ChEls) improve cognitive functions in Alzheimer's disease (AD) and other forms of dementia. Evaluation of treatment efficacy is based mainly on subjective assessment tools which includes standardized neuropsychological tests. Therefore, an additional objective tool for the evaluation of drug response is necessary. Thirty two patients were treated with ChEls for dementia (tacrine 19, donepezil 5, rivastigmine 8). Cognitive response was assessed before ChEls (baseline) and after 26 weeks, as optimal tolerated doses were achieved and maintained (endpoint). Evaluation included repeated measurements of Mini Mental State Examination (MMSE), ADAS-cog and P300. For statistical analysis we used ANOVA with repeated measures and Pearson correlation coefficient. Results demonstrated improvement of mean ADAS-cog by 2.0 points (from 29.4 to 27.4 p = 0.08) while MMSE remained almost unchanged (20.1 to 19.8). Mean P300 latency reduced significantly by 24 msec (from 383 msec to 359 msec, p = 0.0001) thus reflecting the clinical improvement. However mean amplitudes did not change from baseline to endpoint (13 microvolts). Significant correlation was found between mean ADAS-cog and mean P300 latency at baseline and end-point (R = 0.452 p = 0.014, R = 0.567 p = 0.001 respectively). Strong correlation was found between mean MMSE and P300 latency at Baseline (R = -0.335 p = 0.07), and significant correlation was found at endpoint (R = -0.613 p < 0.001). Our data suggests that P300 is a reliable instrument for assessment of cognitive response to ChEls in demented patients.
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PMID:Evaluation of cholinergic treatment in demented patients by P300 evoked related potentials. 1200 52

Centrally acting cholinesterase inhibitors (ChEIs) improve cognitive functions in Alzheimer's disease (AD) and other forms of dementia. Evaluation of treatment efficacy is based mainly on subjective assessment methods such as standardized neuropsychological tests. Therefore, an additional objective tool for the evaluation of drug response would be most helpful.Thirty-two patients suffering from dementia of several etiologies were treated with ChEIs (tacrine 19, donepezil 5, rivastigmine 8). Cognitive response was assessed pre ChEIs initiation (baseline) and after 26 weeks, as optimal tolerated doses were achieved and maintained (endpoint). Evaluation included repeated measurements of Mini Mental State Examination (MMSE), Alzheimer's disease assessment scale cognitive part (ADAS-cog) and P300. For statistical analysis we used ANOVA with repeated measures and Pearson correlation coefficient. Results demonstrated improvement of mean ADAS-cog by 2.0 points (from 29.4, n = 31 to 27.4, n = 29; p = 0.08) while MMSE remained almost unchanged (20.1, n = 29 to 19.8, n = 28). Mean P300 latency reduced significantly by 24 ms (from 383 +/- 7.9 msec, n = 32 to 359 +/- 7 msec, n = 32; p = 0.0001). However mean amplitudes did not change significantly from baseline to endpoint (13.5 +/- 6.2, n = 31 to 12.8 +/- 6.1, n = 31). Significant correlations were found between mean ADAS-cog and mean P300 latency at baseline and end-point (R = 0.485 p = 0.019, R = 0.626 p = 0.001 respectively, n = 23) and between mean MMSE and P300 latency at baseline and endpoint (R = -0.420 p = 0.046, R = -0.703 p < 0.001 respectively, n = 23). Our data suggests that P300 is a reliable instrument for assessment of cognitive response to ChEIs in demented patients.
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PMID:The clinical use of P300 event related potentials for the evaluation of cholinesterase inhibitors treatment in demented patients. 1276 61


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