SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Purified serum cholinesterase 90 mg was administered to a patient with cholinesterase deficiency. The effect on the action of suxamethonium was studied. The half-life (44.7 h), time constant (64.5 h), rate constant (0.0155 h-1) and distribution volume (2740 ml) of the cholinesterase activity were determined.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
As a continuation of work from this laboratory on anticholinesterase induced pancreatitis, a study of the relationship between reduced serum cholinesterase activity and changes in pancreatic intraductal pressure was undertaken. Pharmakokinetic studies in three dogs revealed rapid reduction in serum cholinesterase activity following an IV bolus dose of the cholinesterase inhibitor 0,0-diethyl-0-(2-isopropyl-6-methyl-4-pyrimidinyl)phosphorothioate. Following each dose of cholinesterase inhibitor, stable levels of cholinesterase inhibition were reached in 30 minutes. In four dogs the pancreatic duct was perfused from the tail of the ventral pancreas and intraductal pressures measured. A total of 25 mg/kg of the cholinesterase inhibitor was given in 5 mg/kg doses 30 minutes apart, and serum cholinesterase measured 30 minutes after each dose. Mean pressures were established over a 15 minute interval. Linear regression analysis of 23 data points revealed a significant (p < 0.001) cumulative dose-related increase in pancreatic intraductal pressure [Pressure (cm saline) = 14.2 + 1.03 x Cumulative Dose (mg/kg)] and significant (p< 0.001) negative correlation between serum cholinesterase activity and intraductal pressure [Pressure (cm saline) = 48.0 - 0.057 x Esterase Activity (mU/ml)]. These data suggest that, in dogs, reduced cholinesterase activity is directly related to increased pancreatic intraductal pressure, and it may be a factor in the pathogenesis of pancreatitis.
The activity of locust ganglia cholinesterase is found to depend on concentrations of acetylthiocholine (ATC), propionylthiocholine (PTC) and butyrylthiocholine (BTC); that of carboxylesterase--on concentration of p-nitrophenylacetate (25 degrees, pH 7,5). The activity of cholinesterase is inhibited by an excess of ATC and BTC, but is unaffected by an excess of PTC. At concentrations greater than 0.01 M PTC is hydrolyzed faster than ATC at optimal (1.10(-3) M) concentration. The cholinesterase hydrolysis of BTC proceeds slower than that of ATC and PTC. The bimolecular constants (kII) of the rate of cholinesterase and carboxylesterase interaction with structurally different organophosphorus inhibitors (OPI) were determined. It was found that methylsulfomethylates of O-alkyl-S (beta-ethylmercaptoethyl) methylthiophosphonates are stronger inhibitors of cholinesterase than carboxylesterase; on the contrast, their uncharged analogs are stronger inhibitors of carboxylesterase, since the substitution of the sulfide sulphur for the sulphonic one strongly decreases the anticholinesterase activity and slightly increases the anticarboxylesterase activity of these OPI. O-alkyl-S (carbomethoxymethylmercaptomethyl) methylthiophosphonates inhibit carboxylesterase stronger than cholinesterase. The inhibitory activity of diisopropylthiophosphates towards cholinesterase is much lower than that of the corresponding diethylthiophosphates, while the activity of the former towards carboxylesterase is approximately the same as the activity of diethylthiophosphates or more strongly pronounced. Diisopropylfluorophosphate is a potent inhibitor of carboxylesterase. The data obtained provide evidence for differences in the structure of the active sites of cholinesterase and carboxylesterase. The carboxylesterase has no anionic sites. Moreover, the active surface of this enzyme interacting with the leaving part of OPI possesses, a site which prevents the absorption of cationic OPI and favours the interaction with the OPI containing the carboxyether group. The esterastic site of carboxylesterase is larger than that of cholinesterase and can predominantly interact with OPI having a bulky phosphoryl part.
Although quantitative tests of some hepatic functions have been well established, the determination of serum cholinesterase activity continues to be commonly used in their stead. A critical comparison of the serum cholinesterase activity with these quantitative tests, however, is still lacking. Serum cholinesterase activity was therefore simultaneously compared with galactose elimination capacity (GEC), initial BSP-disappearance rate (BSP-ki), and serum albumin levels in 19 healthy control subjects and 46 patients with various chronic liver diseases. Serum cholinesterase activity was less discriminating between controls and patients than BSP-ki. It appears poorly suited, therefore, as a screening test for mild liver disease. Rank correlations between serum cholinesterase activity and GEC, BSP-ki, and serum albumin were statistically higher significant (r = 0.65, r = 0.74, and r = 0.80 respectively). On a statistical basis, serum cholinesterase activity may, therefore, be regarded as an index of the functional reserve of the liver. Evaluation of individual cases, however, revealed some clinically relevant discrepancies. It is concluded, therefore, that for accurate follow-up studies measurements of serum cholinesterase activity may be insufficient substitutes for the quantitative tests.
Pancuronium causes a powerful and highly selective inhibition of human serum cholinesterase in vitro. The inhibition was studied in serum from 14 individuals of both sexes (5-60 years of age) with normal reactions to suxamethonium. Pancuronium, in a concentration of 2.3 x 10(-7) M, caused a 50% inhibition of the enzymatic hydrolysis of acetylcholine, when this substrate was present in a concentration of 10 x 10(-3) M. The same I50 value was also found for a commercial preparation of human serum cholinesterase. The inhibition was reversible and competitive in type. Pancuronium inhibition of the acetylcholinesterase in human red blood cells and from the electric eel was more than one thousand times weaker. Thus pancuronium is one of the most selective inhibitors of serum cholinesterase described so far. The in vivo activity of the serum cholinesterase in four patients receiving pancuronium 0.1 mg/kg decreased, during the first 3 min, by 60-80%, from the pre-induction value. After this a slow recovery occurred with 40% depression remaining at 45 min after the injection. The tachycardia produced by pancuronium may be related to this selective inhibition of serum cholinesterase. It is suggested that relaxants which selectively inhibit serum cholinesterase also selectively block the cardiac muscarinic receptors.
A study is presented on the activity of cholinesterase (substrate acetylcholine) and of arylesterase (substrate phenylactate) in proteinuria, classified according to the results of electrophoresis of glomerular and tubular proteinuria. Comparison is made with the corresponding serum. The urine is concentrated by dialysis on polyethylene-glycol to 60 g protein per 1000 before determination of the activities. In the presence of equal quantities of protein, cholinesterase is slightly more active in glomerular than in tubular proteinuria. In selective glomerular proteinuria, cholinesterase and arylesterase are less active than in cases with little or no selectivity. Comparison with serum, in each individual case, indicates that the ratio of activity in concentrated urine to that in serum, is higher for cholinesterase and arylesterase in tubular than in glomerular cases, whereas the reverse is true in urine at its natural concentration, on account of the lower degree of proteinuria in tubular cases. The ratio of cholinesterase to arylesterase activity in concentrated urine and serum is determined. Since cholinesterase activity is greatly increased in glomerular cases (nephrosis) this ratio is on average markedly higher in glomerular proteinuria than in serum, whereas it is similar in urine and serum of tubular cases. These results, seen in the light of the molecular weights of the enzymes, are difficult to interpret with certainty, especially as regards tubular proteinuria.
The purpose of the study was to determine the magnitude and the aetiology of alterations in serum cholinesterase activity (pseudocholinesterase) in burned patients. Sixty burned patients with an estimated area of burn between 3 and 72% of body surface were investigated. Serum cholinesterase activity, serum albumin concentration and serum bilirubin were measured at various time intervals. The magnitude as well as the rate of fall of serum cholinesterase activity was found to be closely correlated with the severity of burn injury. Minimum levels were often reached 5 to 6 days after the burn injury, at which time the activity might have been depressed by more than 80 per cent. In the most severely burned patients, the activity sometimes remained low for months despite wound healing. Apart from the severity of the burn injury in the individual patient, several important factors determined the level of serum cholinesterase activity at a given time. These included the presence or absence of local or systemic infections, the event of recent surgery such as slough removal or skin grafting, and blood transfusions. The decrease in serum albumin concentration following the burn injury occurred earlier than the decrease in serum cholinesterase activity. Minimum levels were often reached during the first 24 h, after which time the concentration rose to reach fairly constant but decreased levels after 4 to 5 days. Apart from this initial phase, the changes in serum albumin concentration were roughly proportional to the changes in serum cholinesterase activity. The possible reasons for these findings are discussed.
Tests were set up on 73 Citellus fulvus to study the influence exerted by different doses of vitamin E (4 and 8 mg) introduced per os on the activity of the total cholinesterase in various divisions of the central nervous system and also the part played by the hormonal and seasonal factors in this effect. Each test series lasted 30 days (in spring, summer and autumn). The cholinesterase activity was determined after Vensen and Segonzak (1968). The results of the experiments revealed some characteristic trends in the change of the cholinesterase activity occurring under the effect of vitamin E that depended upon a number of factors, such as: the dose of tocopherol, the sex of the animal, time of the year, the brain division under study and the seasonal dynamics of the initial activity. It is shown that in the brain sectors where a material difference existed in the cholinesterase activity between the control males and females it vanished under the effect of tocopherol. On the other hand, in the brain sectors where no such difference existed, it appeared under the effect of tocopherol. The regular character of changes in the cholinesterase activity of the brain and spinal cord produced by different doses of vitamin E suggest the possibility of the brain cholinesterase activity disorders to a play a part in the development of neuro-muscular pathology in cases of the E vitamin deficiency.
Developing mammals are markedly more sensitive to acute toxicity from exposure to a variety of organophosphorus (OP) pesticides. The present study examined dose-related inhibition of both brain and plasma cholinesterase activity in neonatal and adult rats exposed to sublethal doses of one of three common OP pesticides, methyl parathion, parathion and chlorpyrifos. Effective dose 50 (i.e., ED50 or dose which would inhibit 50% of the cholinesterase activity) values were determined and then correlated with an indicator of acute toxicity, the maximal tolerated dose (MTD). It was found that ED50 estimates for both brain and plasma cholinesterase correlated highly (r = 0.932-0.992) with previously derived MTD values. In no case was there a significant difference between in vivo brain and plasma cholinesterase inhibition across doses in neonatal rats was high (r = 0.962-0.975) but lower in adults (r = 0.700-0.943). The results suggest that in vivo inhibitory potency of the three OPs towards either brain or plasma ChE activity is highly correlated with sensitivity to acute toxicity in both neonatal and adult rats. Additionally, under defined experimental conditions, plasma ChE inhibition may be a useful quantitative index for the degree of brain cholinesterase inhibition following OP exposures.
Highly purified multiple forms of brain cholinesterase were isolated by a new method. Eight forms were identified as acetyl cholinesterases, seven forms--as butyryl cholinesterases, four forms--as mixed acetyl- and butyryl cholinesterases and four forms--as aliesterases. Biosynthesis of multiple forms of brain cholinesterase was monitored by following incorporation of 14C-glycine into the purified fractions. Cats were killed at different periods (3 hrs, 3,6 and 9 days) after intoxication with isopropyl hydroxymethyl fluorophosphate. The restoration of the enzymatic activity after the inhibition did not correspond to the incorporation of the labelled amino acid into the enzyme protein. There was a transcient increase in the incorporation of the label after an increase in acetylcholine concentration.
The electronhistochemical localization of the cholinesterases of developing chick heart muscle cells has been studied with the aid of a substrate which incorporates an enzyme-susceptible thiolester group and a diazonium group into the same molecule. The embryonic chick heart exhibits cholinesterase activity from Hamilton-Hambruger stage 3 through to four days post hatching. Although enzyme activity is not demonstrated in every location at all stages studied, it has been observed on the nuclear envelope, golgi complex, rough and smooth endoplasmic reticulum, mitochondria and myofilaments. A change in the type of activity has been demonstrated, acetylcholinesterase is found during the first fourteen days of development but thereafter, non-specific cholinesterase is seen instead. As nerves have not been found in relation to the working myocardium, further support is given to the concept that an acetylcholine-cholinesterase system of myogenic origin is involved in spontaneous contraction. Consideration of the distribution of enzyme within the myocardial cell, raises the possibility that cholinesterase may be concerned in a regulatory mechanism of protein synthesis, a suggestion made previously in connection with liver cells.
Cholinesterase activity in the low density lipoprotein fraction of serum is increased in types IIa, IIb and IV hyperlipoproteinemic patients, whereas only types IIb and IV show increases in serum cholinesterase activity. In obese patients, cholinesterase activity is increased both in the serum and low density lipoprotein fraction only when hyperlipidemia is present. Cholinesterase activity is also found to increase in proportion with increases in low density lipoprotein, cholesterol, and triglycerides both in the serum and low density lipoprotein fraction. We suggest on the basis of these findings that cholinesterase has a function in lipid and lipoprotein metabolism.
Japanese quail (Coturnix coturnix japonica) were dusted with 5% carbaryl to determine if this topical treatment would alter plasma and brain cholinesterase activities. Within 6 hours after dusting, plasma cholinesterase activity was depressed compared with controls, the depression averaging 20% for females and 27% for males. By 24 hours the cholinesterase activity of females had returned to normal, but the cholinesterase activity of males remained depressed. Brain cholinesterase activity was not affected by the treatment, and there were no overt toxic signs.
The expression of the axial terotogenesis and the cholinesterasic activities have been studied simultaneously in the Quail embryo. High concentration of malathion (1 000 microgram) slightly reduces the cholinesterasic activities and does not produce morphogenetic disturbance. Bidrin (250 microgram) and parathion (100 microgram), strongly inhibit the cholinesterasic activities producing drastic axial deformities. The use of graduated concentrations of parathion shows that these axial abnormalities take place with a high level of cholinesterase inhibition. With organophosphorus, there is a good correlation between the axial teratogenesis and the cholinesterase inactivation.
The report pertains to some data on the cholinesterase activity in the blood serum and CSF of 62 patients with epilepsy, in correlation with different clinical characteristics (the severity of the disease, the character of the EEG, frequency of seizures, treatment efficacy, etc). In 86,8% of the cases there was a significant increase in the activity of serum cholinesterase. Increased cholinesterase activity correlated only with pronounced pathological changes in the EEG (reverse correlation) and the efficacy of treatment (direct correlation). After surgical treatment of 9 cases there was a drop in the cholinesterase activity of the blood serum and CSF, which correlated with an improvement in the general state of the patients. On the basis of personal experience, as well as literary data, it is assumed that an increase in the cholinesterase activity in epileptic patients is not related to the main etiological factors of this disease but is rather a secondary change, a peculiar "symptom" of the disease.