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[Successful treatment of three elderly patients suffering from prolonged delirium using the cholinesterase inhibitor rivastigmine].

Delirium is commonly encountered in elderly patients in general hospitals. Most patients with delirium respond well within 12 days of commencement of treatment with haloperidol. A significant number of patients, however, does not improve. Three elderly male patients aged 85, 79 and 81 respectively suffering from prolonged delirium and unresponsive to haloperidol or atypical anti-psychotic drugs, responded well within days to treatment with rivastigmine--a cholinesterase-inhibitor. It was very well tolerated. In The Netherlands cholinesterase inhibitors are registered for the symptomatic treatment of Alzheimer's disease. There is some evidence, both from animal and human experiments, that cholinergic deficiency plays a role in certain types of delirium. Therefore treatment of delirium with a cholinesterase-inhibitor seems logical. Controlled studies are needed to evaluate the effects of these types of drugs in patients with prolonged delirium.

Aged↗

Evaluation of cholinesterase to differentiate pleural exudates and transudates.

AIMS AND OBJECTIVES: The present study was undertaken to evaluate the usefulness of pleural fluid cholinesterase (PChE) level in pleural fluid and its ratio to serum cholinesterase (P/SChE) in order to differentiate transudates and exudates and to compare their diagnostic efficacy with the Light's criteria. MATERIAL AND METHODS: A total of 110 patients of pleural effusion of diverse etiology were studied. Eighty patients were of exudative pleural effusion of tubercular, malignant or parapneumonic origin and 30 patients were of transudative effusion. Cholinesterase was estimated in the pleural fluid and serum in all the patients. RESULTS: The mean PChE and P/S ChE were significantly higher in exudates as compared to transudates (p < 0.001). P/S ChE was 0.79 +/- 0.45 and 0.14 +/- 0.11 in exudates and transudates, respectively. When a cut-off value of 469 IU/L for PChE was taken for the diagnosis, it was found that 10% of exudates and 2.5% of transudates were misclassified. However percentage of misclassification decreased to 1.25% in exudates and 3.3% in transudates when the cut-off value of 0.24 for P/S ChE ratio was used. Using Light's criteria, a sensitivity of 91.25% and specificity of 90% with positive predictive value (PPV) of 96.05% and negative predictive value (NPV) of 79.42% was observed. However using P/S ChE, the PPV was 98.75% and NPV was 96.67%. CONCLUSIONS: The estimation of PChE and P/SChE ratio had better discriminatory capacity than Light's criteria. It is cost effective and more specific, therefore its routine estimation is recommended.

Adult↗

[Acute organophosphorus pesticide poisoning and cholinesterases activities].

Suicides attempts with an organophosphate pesticide still occur in Brittany, an agricultural French area. The acute poisoning due to this nerve agent, responsible for the inhibition of the cholinesterases enzymes, is severe and can be fatal. The diagnosis is based on the decrease of cholinesterases activity, an assay which has been performed because of the patient context. The measurement of butyrylcholinesterases activity in emergency guarantees an appropriate and rapid management of the patient in order to rapidly regenerate cholinesterases. Even if the decrease level of butyrylcholinesterases activity does not give a significant prognostic value, its follow-up with time indicates the efficacy of the treatment and the gradual remission. In routine the measurement of acetylcholinesterase activity is more useful for the biological follow-up of subjects exposed to organophosphate phytosanitary compounds.

Acute Disease↗

[Spectral study of the peripheral site of ligand binding in the active center of cholinesterases from different natural sources].

An increased ethidium bromide fluorescence at 610 nm was observed in the presence of cholinesterases from some natural sources, and a new fluorescence band appeared in the 500-570 nm region. The data obtained suggest a resonance energy transfer from the cholinesterase-ethidium bromide complex to a free ethidium bromide molecule. The structure of the peripheral ligand binding sites in the active center of bovine erythrocyte acetylcholinesterase, horse serum butyrylcholinesterase, and squid ganglia cholinesterase proved essentially similar.

Animals↗

Pretreatment postural blood pressure drop as a possible predictor of response to the cholinesterase inhibitor velnacrine (HP 029) in Alzheimer's disease.

The failure of cholinesterase inhibitors to produce noticeable improvement in about half of patients with Alzheimer's disease (AD) may result from heterogeneity of neurotransmitter abnormalities in this disorder. This study examined whether pretreatment postural blood pressure (BP) drop, which presumably reflects sympathetic response, differed in patients who were responders or nonresponders to the cholinesterase inhibitor, HP 029. Twenty-three AD patients completed a double-blind dose-finding phase of a clinical trial in which four doses of HP 029 and placebo were administered. Evaluation for efficacy occurred after 7 days of treatment at each dose. Of the 23 patients, 12 were classified as responders in the dose-ranging phase of the study. Nonresponders demonstrated significantly greater decreases in pretreatment systolic postural BPs when going from a supine to sitting position than did responders. The greater postural BP drop in nonresponders may identify a subgroup of AD patients that responds poorly to cholinesterase inhibitors.

Aged↗

New techniques to measure blood cholinesterase activity in domesticated animals.

A macromethod and a semimicromethod were developed to measure erythrocyte acetylcholinesterase activity in cattle, sheep, goats, horses, dogs, and swine, and to measure plasma cholinesterase activity in horses, dogs, and swine. Comparison of the 2 methods with erythrocytes of sheep, cattle, goats, and horses indicated both methods gave similar results. They can be done in a shorter time and are more sensitive than Michel's method. Normal deltapH values per minutes, with standard deviations for blood cholinesterase activity of animals of different ages, sexes, breeds, and species, were: 0.76 +/- 0.12/30; 0.65 +/- 0.10/15; 0.69 +/- 0.19/45; 0.78 +/- 0.11/45; 0.63 +/- 0.11/45; and 0.71 +/- 0.06/25 for sheep, cattle, goats, horses, dogs, and swine erythrocyte acetylcholinesterase, respectively; and 0.66 +/- 0.18/20; 0.67 +/- 0.20/30, and 0.46 +/- 0.05/60 for horses, dogs, and swine plasma cholinesterase, respectively. It was shown that either the chloride or the iodide salt of acetylcholine can be used as the enzyme substrate. tin blood samples stored at 5 C for 24 hours, there was no significant change of the enzymatic activity.

Acetylcholinesterase↗

[Dynamic study of blood cholinesterase activity of paranoid schizophrenic patients].

A comparison of the cholinesterase blood activity with the clinical traits of the disease in 64 patients with paranoid schizophrenia treated by majeptile and haloperidol detected 2 variants in the reactivity of the enzyme link of the cholinergic system. A fluctuation of the cholinesterase activity of the sinusoid type (Ist variant) seen in patients with paranoial and hallucinatory-paranoid syndromes with a remission up to a year and more, speaks in favour of a relatively preserved compensatory-adaptive mechanisms in the neurohumoral regulation. The absence of fluctuation in the cholinesterase activity during the whole period of treatment (2nd variant) was characteristic of patients with negative results of treatment.

Adult↗

[Electrophoresis of cholinesterases of the cerebrospinal fluid in the Guillain-Barré syndrome].

Polyacrylamide gel electrophoresis of cholinesterase from cerebrospinal fluid was performed in 22 patients with Guillain-Barré syndrome. Fifteen of these patients had an abnormal cerebrospinal fluid with emergence of a second electrophoretic migration band corresponding to non-specific cholinesterase. Among 182 patients with a variety of diseases who served as controls, only one presented with this abnormality. From these data the sensitivity and specificity of cerebrospinal fluid cholinesterase electrophoresis were calculated at 68 and 99 percent respectively. The second migration band seems to appear early in the course of the disease and disappears when the patient is cured. Moreover, the occurrence of this band is correlated with the severity of the condition, as shown by a greater number of patients under artificial ventilation and by a longer stay in intensive care unit. Cerebrospinal fluid electrophoresis could be used as a prognosis factor.

Adolescent↗

[Cholinesterase activity of sperm from rams infected with Brucella ovis].

Studied were the indices of cholinesterase activity of semen taken from 23 normal rams and 23 rams infected with Brucella ovis, the latter being positive by the complement-fixation test and showing a varying deterioration of the semen production. The results obtained were processed biometrically. Established were dependable differences. The cholinesterase activity of semen of brucellosis-affected rams proved four times higher than that of normal rams' semen: 39.45 +/- 5.49 microleter TO2 for 1 hour as against 174.15 +/- 9.97 microleter. A reverse correlation was established between the values of the cholinesterase activity, and the pH value and the percent of pathologic forms of spermatozoa.

Animals↗

In vivo and in vitro cholinesterase inhibitor property of the antitumor agent caracemide.

The antitumor agent caracemide [N-acetyl-N-(methylcarbamoyloxy)-N'-methylurea] has been observed to induce signs of cholinergic activation in both animal and human studies at high clinical and toxic levels. The present study was designed to further characterize the ability of caracemide to inhibit cholinesterase both in vivo and in vitro. Caracemide produced a time-dependent inhibition of purified acetylcholinesterase, pseudocholinesterase and rat brain homogenate cholinesterase with IC50 values of 0.60, 0.55 and 17.8 microM, respectively, at the maximal time point of inhibition. Analysis of Lineweaver-Burke plots derived from inhibition of brain homogenates revealed predominantly competitive type inhibition at both initial and maximal incubation times. Intravenous administration of caracemide to rats resulted in a dose-dependent inhibition of brain cholinesterase activity, with the greatest inhibition occurring in the cortex.

Animals↗

Erythrocyte and plasma cholinesterase activity in normal pregnancy.

Erythrocyte acetylcholinesterase and plasma cholinesterase was estimated in 50 normal pregnant women and 22 age matched normal non-pregnant women. Plasma cholinesterase was significantly decreased while erythrocyte cholinesterase was significantly increased during pregnancy. These changes may be related to altered haemodynamics and or other inter-related changes occurring in pregnancy.

Butyrylcholinesterase↗

[Isoenzymes of human blood cholinesterases and their genetic control].

Acetylcholinesterase from human erythrocytes solubilized by 1% Triton X-100 was resolved using polyacrylamide gel electrophoresis into two components. The first one (fast) is more firmly bound to cell membranes than the other. The existence of multiple forms (C1-C4) of serum cholinesterase-1 (CHE1) has been established. Electrophoresis in acid medium (pH 4.8) permits to detect the C5 component and a group of supplementary isoenzymes of cholinesterase-2. Individual differences observed in patterns of the CHE2 isozymes are controlled by a pair of autosomal codominant alleles Che2A and Che2B. The serum of subjects with phenotypes Che2AB(C5+) and Che2BB(C5-) showed on the average equal level of cholinesterase activity.

Acetylcholinesterase↗

[Behavior of serum cholinesterase and acetylcholinesterase activity in acute dimethoate poisoning].

With a patient who in suicidal intention had orally taken a larger quantity of Bi 58 EC (dimethoate) especially the behaviour of the serum cholinesterase activity and the whole blood acetylcholinesterase activity was observed over a period of 38 days and it was compared with the clinical appearance. For the serum cholinesterase activity and the acetylcholinesterase activity a three-phase course that with statistically proven adaption could be described only by a three-membered e-function could be shown. Till the 3rd day an extreme decrease of activity of 80-85 per cent occurred. Both cholinesterases provide the same information with regard to the consequences of intoxication. They are only quantitatively different from each other.

Acetylcholinesterase↗

Changes of activities of some transferases, alkaline phosphatase and cholinesterase in the blood of women using oral contraceptives and in vitro influence of these agents on tissular enzyme levels in rat liver.

Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase activities in the blood serum of women taking the oral contraceptive preparation Microgynon through extended periods were raised; the activity of cholinesterase was simultaneously reduced. In rats liver homogenates ethynylestradiol, one of the active components of Microgynon, acted as an inducer of gamma-glutamyltransferase and alkaline phosphatase while leaving aspartate aminotransferase and alanine aminotransferase unaffected, but reduced the level of cholinesterase. Norgestrel, the other active component of the preparation, suppressed the biosynthesis of gamma-glutamyltransferase and alkaline phosphatase while leaving aspartate aminotransferase, alanine aminotransferase and cholinesterase levels unaffected. A mixture of ethynylestradiol plus norgestrel in the mass proportion occurring in Microgynon produced the same effects upon gamma-glutamyltransferase and alkaline phosphatase as ethynylestradiol alone. Estradiol, the parent hormone of ethynylestradiol, lacked the inducing capability of the latter while ethynylpropargyl chloride induced gamma-glutamyltransferase and alkaline phosphatase so it was concluded the inducing effect of ethynylestradiol must be ascribed to the ethynyl radical. Progesterone, the parent of norgestrel, shared the latter's suppressive activity for gamma-glutamyltransferase and alkaline phosphatase biosynthesis, and behaved like its derivative towards the other enzymes.

Adult↗

[Measurement of serum cholinesterase activity: comparison of commercial and laboratory test reagents, enzyme standards and statistical processing of the results].

The commercially available kits (Test-Combination, Cholinesterase, Boehringer, Mannheim and Test-reagent, Cholinesterase EC 3.1.1.8, Pliva, Zagreb) and reagents prepared in own laboratory for measuring cholinesterase activity (Ellman method) were tested with respect to their stability and the reproducibility of the activity measurements. The reagents of the three sources were shown to be interchangeable and equally stable over a few weeks. The coefficient of variation for within-run measurements by the Ellman method was 2-3% and that for between-run measurements 6%. The stability of the few enzyme standards (Precinorm E, Precinorm U, NBS-serum and native human serum) for the quality control of the measurements was also tested: the most stable was native human serum.

Cholinesterases↗

[Polymorphism of human serum cholinesterase (EC 3.1.1.8) in Leningrad and Azerbaijan populations].

Polymorphism of human serum cholinesterase (CHE, EC 3.1.1.8.) determined by two autosomal loci Che1 and Che2 was examined among populations of Leningrad and Azerbaidjan. Routine screening and spectrophotometric methods were used to reveal the enzyme variants controlled by Che1 locus, the technique of electrophoretic separation in 7.5% PAAG being used for identification of the variants controlled by Che2 locus. The frequencies of cholinesterase variants were found to be: CHE1U-0.960 +/- 0.0140, CHE1UD-0.023 +/- 0.107, CHE1UF-0.017 = 0.0092, CHE2(5-)-0.926 +/- 0.0187, CHE2(5+)-0.074 +/- 0.0187 for Leningradian population (750 donors) and CHE1U-0.940 +/- 0.0329, CHE1UD-0.060 +/- 0.0329, CHE2(5-)-0.915 +/- 0.0386, CHE2(5+)-0.085 +/- 0.0386 for Azerbaidjanian population (200 pupils). The differences in enzyme variant frequencies were not significant for children (165), donors and persons aged sixty and older (120) for Leningradian population. The frequency of CHE1UD variant was shown to be significantly higher among Azerbaidjanian pupils, as compared to the donors and children of Leningrad. The correlations between the CHE activity and polymorphic enzyme forms, the blood groups AB0, sex and age were determined. Possible ways and mechanisms of formation of genetic cholinesterase polymorphism determined by two autosomal loci are discussed and the role of the anthropogenic factors is noted. The considerable contingent of pharmacological risk is found among populations examined, that is those having potential hypersensitivity to some local anaesthetics, non-narcotic analgetics and depolarising myorelaxants.

Adolescent↗

[Comparison of the cholinoreceptor and cholinesterase properties of the frog Rana temporaria and the squid Todarodes pacificus].

Studies have been made on the interaction of several groups of quartenary ammonium salts with cholinoreceptors of m. rectus abdominis of the frog Rana temporaria, and isolated m. retractor infundibuli of the octopus Todarodes pacificus, as well as with cholinesterases of the frog brain and visual ganglia of the octopus. The derivatives of polymethylene bis(trimethylammonium) compounds, being cholinomimetic drugs for frog muscle, do not exert cholinomimetic influence on octopus muscle. The same difference with respect to their effect on frog and octopus receptors was found in anabazin derivatives. Among amide derivatives of acetylcholine, the strongest mimetic effect on cholinoreceptors of both animals was exhibited by a piperazine isolog with gauche-conformation, whereas N-methyl isolog with trans-conformation was found to be the strongest inhibitor of cholinesterases. Cholinoreceptors and cholinesterase of the octopus were less sensitive to the effect of the investigated quartenary ammonium salts than those of the frog.

Abdominal Muscles↗

[Cholinesterase activity as a prognostic test in phalloidine mushroom poisoning].

The phalloidine mushroom poisoning is an exogenic intoxication with specific action of the mushroom toxins on the liver and its functions. The dynamic follow up of serum cholinesterase activity in patients with phalloidine intoxication revealed that it was significantly decreased in the patients who died in comparison to those who survived. In the patients who survived and recovered the serum cholinesterase was moderately decreased and later increased. As a protein product synthesized in the liver the serum cholinesterase is a good marker of the protein-synthesizing function of the liver in patients with phalloidine intoxication and may be used as a prognostic test for its outcome.

Acute Disease↗