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 organophosphorus compound 0,0-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate was introduced as an insecticide, trichlorfon, in 1952 (Lorenz et al., 1955) and as a drug, metrifonate, in the treatment of schistosomiasis in 1960 (Lebrun and Cerf, 1960). This organophosphorus compound is unique in that it has been claimed not to be a direct acting cholinesterase inhibitor but being transformed nonenzymatically into an active component dichlorvos, 2, 2-dichlorovinyl dimethyl phosphate (DDVP). The evidence for this transformation has mostly been indirect. Recently it has been proved chemically and quantitatively that this transformation occurs in the animal body (Nordgren et al., 1978). Metrifonate is the sole organophosphorus compound currently studied clinically in schistosomiasis. A substantial therapeutic effect is obtained only in Schistosoma haematobium infections. In this review on available data of metrifonate it is suggested that further more detailed studies of both S. haematobium and S. mansoni are necessary. This should include studies of the enzymic properties of the worms and the reaction of their esterases towards both metrifonate and DDVP as well as the pharmacokinetics of these compounds in man. In addition there are still unsolved discrepancies reported regarding organ toxicity of the compound which may, however, be due to different grades of parity of the test material.
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PMID:Metrifonate. Summary of toxicological and pharmacological information available. 36 95

The indications, the contraindications, and the characteristics of the antimonial and nonantimonial drugs clinically available for the treatment of human schistosomiasis are outlined. Of the antimonial compounds, antimony potassium tartrate or antimony sodium tartrate, both given by the intravenous route, are effective against Schistosoma japonicum, S. mansoni, and S. hematobium, but the production of severe side effects limits their use outside the treatment of individuals. Sodium antimonyl gluconate is less effective against S. mansoni and S. hemotobium and is also given intravenously. Of those antimonial compounds given intramuscularly, antimony dimercaptosuccinate is the most effective against all three common human schistosomes. Four available nonmetallic schistosomicides are considered. Niridazole, orally administered, is effective against all three common species of schistosome infecting man, but activity is maximal against S. hematobium. Many minor side effects have been described, but the major and most important side effects, neuropsychiatric symptoms and signs, are fortunately rare. Lucanthone hydrochloride, of moderate efficiency when given orally for S. hematobium or S. mansoni infections, is probably best used as a suppressant in small doses. Troublesome gastrointestinal toxicity limits its therapeutic use. Metrifonate, a cholinesterase-inhibiting organophosphorus compound, is effective only against S. hematobium. Clinical tolerance is very good. Hycanthone mesylate is highly effective against S. mansoni and S. hematobium but ineffective against S. japonicum. It is given as a single intramuscular dose. Many contraindications to its use exist, and acute hepatotoxicity has occurred infrequently. Its association with mutagenicity in certain experimental test systems has stimulated numerous ongoing studies to clarify the implications of its use in humans.
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PMID:Clinically available antischistosomal drugs. 120 68

The hepatosplenic form of Schistosoma mansoni infection contributes considerably to morbidity and mortality in endemic areas. The present study investigated serum protein concentrations and serum enzyme activities of 58 Sudanese patients with hepatosplenic schistosomiasis. All of them had a history of infection with S. mansoni and one or several episodes of oesophageal bleeding due to portal hypertension. Diagnosis was based on clinical (n = 24), ultrasonographical (n = 18) and histological (n = 16) grounds. The control group consisted of 40 Sudanese healthy blood donors. Serum albumin was found to be significantly lower in patients with hepatosplenic schistosomiasis (median = 37 g/l) than in controls (median = 47 g/l). Serum enzyme analysis revealed only minimal alterations of cellular enzyme activities, but a marked decrease of cholinesterase activity. Serum albumin concentration correlated significantly with cholinesterase activity. We conclude that liver function in patients with schistosomiasis and portal hypertension is partially disturbed. Low serum albumin and low cholinesterase activity reflected an impaired protein synthesis of the liver. Destruction of parenchymal liver cells was mild or absent.
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PMID:Enzyme activities and protein concentrations in serum of patients with hepatosplenic schistosomiasis. 170 59

Thirty patients suffering from active intestinal S. mansoni infection, were classified into 3 groups. The first group: 13 cases with early active intestinal schistosomiasis without hepatosplenomegaly. The second group: 11 cases with hepatosplenomegaly and the third group: 6 cases with splenomegaly and ascites. Also 10 normal individuals were included as a normal control group. Histopathological examination of rectal mucosa showed hyperaemia with extravasation of blood in early cases and granulomatous lesions in the second group with hepatosplenomegaly. The structural changes were severe in the late ascitic group. In this group the rectal mucosal glands showed distorted irregular tubular branching in addition to the granulomatous and the fibrous reactions. Histochemical studies including periodic acid schiff, alkaline phosphatase and acetyl cholinestrase reactions were done. Using the periodic acid shiff stain, the goblet cells showed strong reaction for neutral mucin in cases of group I (early cases) and group II (late hepatosplenomegalic cases). In group III (late ascitic cases) the goblet cells were faintly stained. A notable difference was observed between the lightly and heavily infected patients of this group. No alkaline phosphatase reactivity could be identified in rectal crypts of patients and controls. Alkaline phosphatase reactivity was sharply localised in S. mansoni egg shell. There was obvious decrease in the acetyl cholinesterase stained nerve fibres in the rectal mucosa of all studied patients. The decrease was more in chronic and heavily infected cases rather than in the acute and lightly infected ones.
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PMID:Histochemical studies on rectal mucosa in active intestinal schistosomiasis. 190 99

This study was initiated to investigate the long term effect of exposure to organophosphorus pesticides (O.P), with consideration to bilharziasis (an endemic parasitic disease in Egypt, usually associated with liver fibrosis). Serum levels of choline esterase (Ch E), glutamic pyruvic transaminase (SGPT), alkaline phosphatase (Alk. Ph.) and proteins were estimated among 100 (O.P.) sprayers with various duration of exposure (3 to 15 years) and among 60 controls. O.P. sprayers showed significantly higher, SGPT and Alk. Ph. and lower Ch E and serum proteins than the controls. Among sprayers, duration of exposure to O.P. was significantly correlated with their levels of Ch E, SGPT, and Alk. Ph. but not with serum proteins. Compared to other parameters, SGPT seems to be a good indicator of the hepatic effect of long term exposure to O.P. Bilharzial infection did not modify the effect of O.P. pesticides on the above mentioned parameters. Ch E of smoker sprayers was significantly less than that of non smokers. This was attributed to increased absorbtion of O.P. during smoking at work places.
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PMID:Serum choline esterase and liver function among a group of organophosphorus pesticides sprayers in Egypt. 213 58

In a controlled clinical trial, Tanzanian schoolchildren with urinary schistosomiasis, many of whom had coexisting hookworm infection, were randomly allocated to one of three groups that were treated with doses of 7.5, 10.0, and 12.5 mg per kg of body weight, respectively, of metrifonate, orally, up to 3 times at 14-day intervals. No serious side effects were observed during or after the administration of single or repeated doses. A few hours after medication, plasma cholinesterase was almost completely inhibited, regardless of the dose given, while erythrocyte cholinesterase was almost completely inhibited, regardless of the dose given, while erythrocyte cholinesterase was inhibited down to 40-60% of the pretreatment level, depending on the dose. Plasma cholinesterase was inhibited to a greater extent than erythrocyte cholinesterase but showed a more rapid recovery of activity. A moderate accumulation of unreactivated erythrocyte cholinesterase occurred at all dose levels with this regime. Four weeks after the last dose of drug, plasma cholinesterase activity was nearly normal in all the treated children. Erythrocyte cholinesterase activity returned to normal 8-15 weeks after the last dose. The therapeutic results confirmed the efficacy of metrifonate against Schistosoma haematobium. There was an additional though less striking effect against hookworm.
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PMID:Effect of metrifonate on blood cholinesterases in children during the treatment of schistosomiasis. 453 36

Muscle action potential amplitude recorded from abductor pollicis brevis in response to nerve stimulation was measured in 55 children during treatment of urinary schistosomiasis with metrifonate (3 doses at 2 weekly intervals). Mean erythrocyte cholinesterase activity was 52-75% of pretreatment value in different groups when examined electrophysiologically. Twenty-six children acted as controls. There was no difference in amplitude between control and exposed subjects 2 weeks after the 2nd dose. Six hours after the 3rd dose, amplitude was larger in some subjects. This effect was not related to dose or degree of cholinesterase inhibition and was thought unlikely to be the result of treatment. Three children who received the highest dose of metrifonate had developed repetitive activity 6 hr later. The criteria for its identification are described.
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PMID:Effect on neuromuscular transmission of repeated administration of an organophosphorus compound, metrifonate, during treatment of children with urinary schistosomiasis. 628 97

The least detectable effect of acute cholinesterase inhibition (produced by edrophonium) in a normal subject is described. It consists of repetitive activity following the muscle response to a single nerve stimulus. Repetitive activity does not follow a second response at an interval of 30 msec. or 80 msec. There is no change in amplitude of the response to a single stimulus; nor to a second stimulus with the smallest dose of edrophonium. With higher doses of edrophonium the amplitude of the second response is reduced. 55 children were studied during treatment of urinary schistosomiasis with metrifonate (3 doses at 2 weekly intervals). No change in evoked muscle action potential amplitude attributable to treatment was detected. 3 children developed some repetitive activity 6 hours after their third dose, when erythrocyte cholinesterase inhibition was approximately 50%.
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PMID:Effect of metrifonate on neuromuscular transmission. 628 88

Metrifonate (0,0-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate) is an organophosphorus compound where there are excellent possibilities to make studies in man. Metrifonate and its rearrangement product dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP) were studied in human blood from schistosomiasis patients treated with Bilarcil. A mass fragmentographic technique was employed. Deuterium labelled variants of the substances were used, both as internal standards and to compensate for DDVP formed during the workup procedure. The amount of DDVP in plasma was about 1% of the amount of metrifonate. In erythrocytes the corresponding amount of DDVP in percent of metrifonate was half or less. Both compounds reached peak levels within two hours and were detectable for at least eight hours. The results were compared to erythrocyte and plasma cholinesterase determinations. Levels of metrifonate and DDVP, together with cholinesterase activity, have also been studied in mouse brain, liver and kidney. It is proposed that metrifonate acts as a slow release formulation for DDVP. Clearance of metrifonate in man occurs primarily via DDVP. Mild vertigo subsiding in a few hours was the most common side-effect.
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PMID:Quantitation of metrifonate and dichlorvos in blood and tissues by gas chromatography-mass spectrometry. 718 87

Twelve patients with hepatosplenic bilharziasis were compared with another twelve control group. They were divided into three subgroups of four patients each. The duration of suxamethonium tacrine apnea was measured in the first subgroup, while in the second subgroup, the suxamethonium tacrine apnea was calculated after a previous dose of suxamethonium. The duration of apnea following two successive doses of suxamethonium was estimated in the third subgroup. The plasma cholinesterase was measured in all patients. The duration of suxamethonium apnea was not different following either the first or second dose. Tacrine prolonged suxamethonium apnea in both groups, but the prolongation was more in bilharzial patients. There was no significant difference in the plasma cholinesterase level in either group.
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PMID:Tacrine-suxamethonium apnea in patients with hepatosplenic schistosomiasis. 725 43


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