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Correlation between whole blood cholinesterase activity and cerebral cortex cholinesterase activity in rats treated with parathion.

Organophosphate and carbamate insecticides are inhibitors of cholinesterases (ChE). The depression of blood ChE activity is frequently used as indicative of exposure to these chemicals. However, it is not known whether the inhibition of blood ChE activity reflects the inhibition of ChE in target tissues (e.g. brain and muscle). In this study we investigated the possibility of using whole blood ChE activity to predict frontal cerebral cortex ChE activity in rats treated with parathion. Twenty four hours after the intraperitoneal administration of several doses of parathion, the activity of ChE in whole blood and the activity of ChE in frontal cerebral cortex were determined in each animal. A high correlation between the two parameters was found (r = 0.96, p < 0.05) and the model of linear regression fitted to the data accounted for 93% of its variability. Thus, these results seem to indicate that 24 hours after the treatment with parathion the effects induced on whole blood ChE activity may be used to predict the effects caused on frontal cerebral cortex ChE activity.

Animals↗

Blood cholinesterase in rats fed an insect resistance apple clone containing a natural cholinesterase inhibitor.

A crab apple clone (Malus brevipes 1021), highly resistant to the apple maggot, is being used in breeding programs developing commercial apple cultivars. This study has discovered that this crab apple contains a natural cholinesterase (ChE) inhibitor that caused a 17.5% in vitro inhibition of rat blood ChE activity. This crab apple also showed a relatively high total (titratable) acidity of 1.28%. The commercial, nonresistant, apple cultivar McIntosh was capable of causing a 7.9% inhibition of blood ChE in vitro. The total acidity in McIntosh was 0.45%. A 4-wk feeding study compared 2 groups of 5-wk-old Fischer 344 male rats fed diets containing 45% of either M. brevipes or McIntosh freeze-dried apples to a third (control) group of rats fed a semipurified diet. In vivo blood ChE activities were similar in all groups of rats, as well as hemoglobin, hematocrit, and red blood cell counts. The liver mixed-function oxidase activity through aminopyrine N-demethylase in the rats fed the apple diets was higher than the controls, but p-nitroanisole O-demethylase activity was induced only in the animals fed the maggot-resistant crab apple. Lowered growth with concomitant lowered food intake, in the otherwise healthy rats fed the maggot-resistant crab apple diet, was attributed to the less palatable, highly acidic fruit. This study indicates that the natural ChE inhibitor in the insect-resistant apple M. brevipes is apparently detoxified upon ingestion.

Animals↗

[Use of hemoperfusion and cholinesterase in acute poisoning with organophosphate cholinesterase inhibitors--clinical analysis of 50 patients].

The authors present a retrospective analysis of 50 patients with acute intoxication with various organophosphate cholinesterase inhibitors who were treated in the course of 8 years by comprehensive conservative and extracorporeal elimination treatment. The mean age of the patients was 38 years. During therapy conservative treatment was used (gastric lavage, repeated lavage of the large intestine, forced diuresis, TMB-4 fusion through activated carbon, amberlite XAD-2 and XAD-4, haemodialysis). A total of 63 haemoperfusions and 15 simultaneous haemoperfusions with haemodialysis were performed. Treatment was successful in 92%. The results of treatment depended on early attendance of the patient in the dialyzation centre, on the onset of intense comprehensive treatment and the concurrent presence of other diseases.

Adult↗

Effect of combined fenthion and cimetidine use in rats on lethality, blood cholinesterase activities, and serum cholinesterase isoenzymes.

H2-receptor antagonists inhibit cholinesterase (ChE) activity. We examined perturbations in ChE isoenzyme patterns and ChE activities of rats from the combined effects of fenthion (FEN) and cimetidine (CIM). Sixty-four female Sprague-Dawley rats were divided into 8 groups. Four rat groups were given FEN or gum arabic solution and each group divided into 2 small groups according to the CIM or gum arabic administration. FEN was administered po at 12.3 mg/kg (1/20 LD50) or 24.5 mg/kg (1/10 LD50) for 14 days or 49 mg/kg (1/5 LD50) every 4 days. CIM was given po at 1,500 mg/kg from days 7 to 13. Samples were collected 3 h after CIM administration on days 8 and 13. CIM did not influence ChE isoenzyme patterns or ChE activity. FEN inhibited both the ChE isoenzyme patterns and ChE activities without producing clinical signs. Although 1 rat in the 12.5 mg FEN/kg + CIM group died on day 10, all rats in other FEN (24.5 mg/kg or 49 mg/kg) + CIM groups died on days 8-10. Differences in suppression of ChE isoenzyme patterns were detectable between the FEN-dosed and FEN + CIM-dosed groups. There were no differences in ChE activities between the FEN-dosed and FEN + CIM-dosed groups. The i.p. administration of 500 mg CIM/kg (LD50) did not suppress ChE activities.

Animals↗

Development of cholinesterase histochemical staining in cerebellar cortex: transient expression of "nonspecific" cholinesterase in Purkinje cells of the nodulus and uvula.

Patterns of "nonspecific" cholinesterase (ChE) and acetylcholinesterase (AChE) activity were studied in developing rat cerebellar cortex by enzyme histochemistry and light and electron microscopy. Three types of ChE histochemical reaction product were observed in cerebellar cortex: (i) ChE is found in capillary endothelium throughout the cerebellum. Capillary ChE staining is present by the time of birth and continues into adulthood. (ii) ChE is found in radial glial fibers and their parent cell bodies, the Golgi epithelial cells. Radial glial fiber staining is mot intense during the first 3 weeks of postnatal life. (iii) ChE is found in Purkinje cells of the nodulus and ventral uvula. No ChE staining of Purkinje cells was seen in other parts of the cerebellum. ChE staining of Purkinje cells appears to be transient, first appearing at Postnatal Day 2 (P2), reaching peak intensity at P7-9, and decreasing to adult levels by P16. AChE activity displays a pattern markedly different from ChE, with staining in deep cerebellar nuclei, in putative mossy fiber terminals, and in Golgi neurons of cerebellar cortex. No evidence was found for transient AChE staining in Purkinje cells in any part of the cerebellum. The function of transiently expressed ChE activity in developing Purkinje neurons is unknown, but may be related to reorganization of cerebellar cortical circuitry associated with growth of mossy fiber afferents.

Acetylcholinesterase↗

The effects of a cholinesterase inhibitor are prominent in patients with fluctuating cognition: a part 3 study of the main mechanism of cholinesterase inhibitors in dementia.

Fluctuating cognition is evidenced in different forms of dementia and is accompanied by electroencephalographic (EEG) abnormalities. The authors hypothesize that cholinesterase inhibitors are effective mostly in patients with fluctuating cognition. Twenty-three patients affected by mild dementia with similar scores on Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog), and Unified Parkinson's Disease Rating Scale evaluation were classified in a group with fluctuating cognition (n = 11) and a group of nonfluctuators (n = 12). All patients were assigned randomly to the branches of a double-blind crossover study of donepezil (DPZ), a 5 to 10-mg dose, versus vitamin E, a 2000 IU dose, for 30 days. MMSE, ADAS-cog, University of California at Los Angeles Neuropsychiatric Inventory (NPI), quantitative EEG, P3 event-related potentials, choice reaction time variability (CRTV) were assessed at baseline and at the end of treatments. At the end of the crossover study all patients received DPZ for 6 months. The dominant EEG frequency variability, low EEG frequencies amplitude, the P3 latency and jitter, CRTV, and NPI was significantly different in the fluctuating cognition group than the nonfluctuating group at baseline (P < 0.001). Short-term DPZ administration induced a significant increase in MMSE scores, reduction of ADAS-cog and of NPI scores (P < 0.003-0.001), increase of EEG alpha activity and reductions of P3 latency and jitter, dominant frequency variability and CRTV (P < 0.009-0.001) in the fluctuating cognition group, and significant increases of MMSE scores (P = 0.03) and a decrease of P3 jitter and dominant frequency variability (P < 0.034-0.041) in the nonfluctuating group. Short-term DPZ effects differed significantly between fluctuating cognition and nonfluctuating patients (0.001). Significant effects of the 6-month observation were observed only in fluctuating cognition patients. Logistic analysis showed that P3 latency predicts the effect of DPZ (P = 0.04, P < 0.01) in the crossover study, and CRTV predicts the effect at the 6-month follow-up.

Aged↗

Modifications of a cholinesterase method for determination of erythrocyte cholinesterase activity in wild mammals.

A method to determine erythrocyte cholinesterase (ChE) activity was modified for use in wild mammals. Erythrocyte ChE of California voles (Microtus californicus) was primarily acetylcholinesterase (AChE), which was similar to the brain and unlike plasma which was primarily butyrylcholinesterase (BChE). Triplicate erythrocyte AChE analyses from individual animals of several species of wild rodents revealed a mean coefficient of variation of 8.7% (SD = 4.3%). Erythrocyte ChE activity of several wild mammals of California revealed that mule deer (Odocoileus hemionus) had the highest erythrocyte AChE activity (1,514.5 mU/ml) and dusky-footed woodrats (Neotoma fuscipes) had the lowest activity (524.3 mU/ml). No ChE activity was found in erythrocytes of several species of birds and fish.

Animals↗

A cholinesterase genes server (ESTHER): a database of cholinesterase-related sequences for multiple alignments, phylogenetic relationships, mutations and structural data retrieval.

We have built a database of sequences phylogenetically related to cholinesterases (ESTHER) for esterases, alpha/beta hydrolase enzymes and relatives). These sequences define a homogeneous group of enzymes (carboxylesterases, lipases and hormone-sensitive lipases) with some related proteins devoid of enzymatic activity. The purpose of ESTHER is to help comparison and alignment of any new sequence appearing in the field, to favour mutation analysis of structure-function relationships and to allow structural data recovery. ESTHER is a World Wide Web server with the URL http://www.montpellier.inra.fr:70/cholinesterase.

Amino Acid Sequence↗