Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of Takatsuki disease, 57-year-old male associated with monoclonal IgA, lambda-type immunoglobulin was treated with recombinant alpha-interferon daily by intramuscular injection with an initial dose of 3 X 10(6) U/day. Four weeks later, gynecomastia was improved and breast pain disappeared. Increases of cholesterol from 84 mg/dl to 135 mg/dl and cholinesterase from 0.24 delta pH to 0.48 delta pH were observed, 8 weeks later. Though, there was no reduction in serum M protein, no decrease in the number of bone marrow tumor cell and no restoration of muscle atrophy and polyneuropathy. No predominant side effect was observed. We conclude that rIFN alpha has a some potential role in the treatment of Takatsuki disease and additional chemotherapy should be considered. Significance of the therapy against Takatsuki disease was discussed.
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PMID:[Therapeutic effect of recombinant interferon alpha on Takatsuki disease]. 235 63

The authors report three cases of poisoning with organic phosphate compounds in children. The first case presented a complex of late signs in the form of toxic polyneuropathy, and two had an acute course. The observation confirmed the view that an at least 7-day hospital stay and 4-week follow-up are necessary in view of great fluctuations in the level of cholinesterase which is often not correlated with the clinical status.
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PMID:[Neurologic complications in organophosphate insecticide poisoning in children]. 314 6

A case of 38 year old man who worked with organochlorinated and Parathion during 5 years is reported. His follow-up was up to 2 years. The onset of the disease was characterized by cholinergic signs, headache, loss of weight, trembling, miokimias, fasciculations, ataxia, myotonic phenomena (in hands only) and motor sensitive peripheral polyneuropathy (affecting the lower limbs symmetrically). Low concentrations of blood cholinesterases confirmed the etiology. Myotonic phenomena disappeared spontaneously 6 months after the initial observation. One year later, the concentration of erythrocyte acetylcholinesterase was found to be low and plasma cholinesterase was normal, suggesting that the patient was carrier of a congenital deficiency of acetylcholinesterase. In literature relationship between myotonia and intoxication due to organophosphorus was not found. The whole clinical picture, cholinergic symptoms, transitory phenomena and spontaneous motor activity could be explained by an excess of acetylcholine. Electromyography (EMG) in the first observation showed neuromuscular transmission blocking characterized by deficiency or absence of voluntary activity, unexcitability of fibular nerves, with fibrillations and positive peaks as described previously with Mipafox (another organophosphorus agent). During 2 years of observation numerous end-plates potentials of muscular fibres persisted in the EMG. A progressive increase in voluntary activity showed by unit motor potential of almost normal amplitude and very increased duration was observed. No potentials of reinnervation were noted. The results of EMG were explained as disturbances of neuromuscular transmission associated with moderate signs of denervation. The Eaton-Lambert's test and the stimulation of a single unit motor potential confirmed disorder of neuromuscular synapses. The histochemistry of brachial biceps showed scattered atrophic and angulated type I and II fibres. Teased-fibres preparations showed nerve fibres with B, C, and G alterations as defined by Dyck et al. indicating axonal degeneration. These results were according to velocity of sensitive conduction. The conduction velocity of fibular nerves was strongly delayed during all the evolution indicating serious disorders of motor nerves myelin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Polyneuropathy caused by parathion: clinical, electrophysiologic and histologic studies of a case]. 665 78

Many organophosphorus compounds, including the organophosphate insecticides, may cause polyneuropathy of delayed onset. An exception is parathion, which has been considered the prototype of nonneurotoxic cholinesterase inhibitors. Nevertheless, we describe a patient with delayed polyneuropathy after suicidal ingestion of parathion.
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PMID:Polyneuropathy after massive exposure to parathion. 719 75

High dose exposure to anticholinesterases which results in symptomatic poisoning can have lasting consequences due to the trauma of intoxication, excitotoxicity, secondary hypoxic damage, and (for some agents) a delayed onset polyneuropathy (OPIDN). The potential effects of low level exposure are less well defined. The most reliable data comes from controlled clinical trials with specific agents. A single dose of sarin or repeated doses of metrifonate or mevinphos, have produced only transient adverse effects at doses causing substantial acetylcholinesterase inhibition. Other data comes from epidemiological surveys. These have often used more sensitive indices than the clinical studies, but are less reliable due to the difficulty of defining exposure and matching control and exposed populations. Subtle, mainly cognitive, differences between exposed and non-exposed populations are sometimes seen. Low level exposure can cause a reversible down-regulation of cholinergic systems, and a range of non-cholinesterase effects that are structure-specific, and do not always parallel acute toxicity. Novel protein targets sensitive to low level exposure to some organophosphates are known to exist in the brain, but their functional significance is not yet understood.
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PMID:Chronic effects of low level exposure to anticholinesterases--a mechanistic review. 1002 7

Organophosphorus compounds, used as insecticides and agents of chemical warfare, are a major global cause of health problems. These irreversible inhibitors of cholinesterase produce three well-recognised clinical entities: the initial cholinergic phase, which is a medical emergency often requiring management in an intensive care unit; the intermediate syndrome, during which prolonged ventilatory care is necessary; and delayed polyneuropathy. In addition, disturbances of body temperature and endocrine function, electrolyte imbalances, immunological dysfunction and disorders of reproduction have been reported in animals and man. Vocal cord paralysis, pancreatitis, cardiac arrhythmias and a wide range of neuropsychiatric disorders are known to follow acute and chronic exposure to organophosphorus compounds. As a result of the inhibition of plasma cholinesterase, there can be increased sensitivity to drugs hydrolysed by this enzyme, e.g. suxamethonium and mivacurium. The inhibition of acetylcholinesterase causes dysfunction at the neuromuscular junction which can produce altered responses to nondepolarizing neuromuscular blockers. Anaesthetists may encounter patients exposed to organophosphorus compounds either following acute poisoning, trauma (warfare) or as patients with a wide range of nonspecific disorders presenting for surgery. The traditional use of oximes and atropine in treatment has failed to reduce the morbidity and mortality associated with poisoning. The roles of agents that have reduced the toxicity of organophosphorus compounds in animal experiments are discussed as potential therapeutic agents. There is an urgent need for accurate information on the problems associated with exposure to organophosphorus compounds. This would best be achieved by collaborative research between technologically advanced countries and developing countries, where organophosphorus compounds are a leading cause of ill health.
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PMID:Organophosphorus poisoning and anaesthesia. 1054 97

The ubiquitous organophosphates present a continuing health hazard in agriculture, public health eradication programmes and as chemical warfare agents. Despite significant progress in understanding the potential mechanisms of toxicity far beyond the commonly accepted mechanism of cholinesterase inhibition in intentional exposures, the precise health effects following occupational exposures are yet to be completely defined. A much greater understanding exists of the clinical features of organophosphate poisoning. These are characterized by a triphasic response involving an initial acute cholinergic phase, an intermediate syndrome (both associated with high mortality) and a disabling but non-lethal delayed polyneuropathy. The delayed polyneuropathy may occur in the absence of the cholinergic or intermediate phases. However, progress is still required in order to improve the quantification and assessment of occupational exposures and the implementation of appropriate preventive measures. Finally, evidence-based guidelines for appropriate or optimal therapeutic interventions following poisoning are required urgently and collaborative work with colleagues in developing countries, where the occurrence of organophosphate exposures is more frequent, may provide the answers.
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PMID:Organophosphate toxicity and occupational exposure. 1502 Jul 23

In recent years a number of studies have drawn attention to the possible neuropsychological sequelae stemming from acute poisoning by certain substances, namely cholinesterase inhibitors. These chemicals, carbamates and organophosphorates (OP), have been used in industry, for washing cattle, as insecticides and even as chemical agents in terrorist attacks and in wars. Nowadays, they are widely used as a pesticide and this is particularly so in regions such as the west of Almeria. The intensive farming in greenhouses carried out in this area, together with the conditions in which these products are used and handled, leads to a relatively high number of cases of poisoning. Yet this is not an isolated fact; the first clinical study to describe cases of poisoning by these substances in workers was published back in 1955. Some of the neurotoxic sequelae deriving from such intoxications are well defined: acute cholinergic syndrome, intermediate syndrome and delayed polyneuropathy provoked by OP (OPIDN). Several studies have been carried out over the past few decades to measure the long term neuropsychological disorders produced by acute poisoning by these substances, and findings suggest that both cholinesterase inhibition and other biochemical phenomena can have permanent neurotoxic consequences. This communication aims to bring some order to the data offered by the different studies by analysing and verifying the evaluation protocols followed, the results of the neurophysiological and neurocognitive biochemical measurements, the type of poisoning and the time elapsed since they occurred, so that they can be summarised and taken as guidelines for possible work to be carried out in the future.
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PMID:[Neuropsychological sequelae of acute poisoning by pesticides containing cholinesterase inhibitors]. 1505 24

There is limited information regarding the management and outcomes of patients presenting with anticholinesterase pesticide poisoning in Australia. Patients presenting to a tertiary referral hospital with anticholinesterase exposures were identified by discharge coding. The medical records of each patient were retrospectively reviewed. Based on clinical outcome, patients were classified as severe or non-severe poisonings. Forty-one presentations were noted between 1990 and 2003. Eight patients (20%) had severe poisoning of which tachycardia, fasciculations with weakness and metabolic acidosis were common manifestations. The diagnosis was delayed in four patients due to the absence of a clear history, which did not influence patient outcomes or put hospital staff at risk of nosocomial poisoning. The median length of hospital stay was prolonged in severe poisonings (20 days) compared to 12 hours in other patients. Two cases of intermediate syndrome were attributed to fenthion and diazinon, and one case of delayed polyneuropathy to trichlorfon. Cholinesterase activities were performed in only 49% of presentations. The overall mortality was 2.4% (1 death) and the mortality in patients with severe poisoning was 12.5%. The incidence of anticholinesterase poisoning in Australia is low. These outcomes were favourable and comparable with other published data. Measures to enhance the knowledge of medical staff supplemented by validated treatment protocols should be developed. For less significant exposures, an emphasis on adequate documentation of cholinergic signs and cholinesterase activities is necessary for rapid triage and may also have potential forensic implications if not performed.
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PMID:Experiences of anticholinesterase pesticide poisonings in an Australian tertiary hospital. 1611 88

Alanine-to-threonine (A to T) substitutions caused by single nucleotide polymorphisms (SNPs) occur in diverse proteins, and in certain cases these substitutions induce self-aggregation into amyloid fibrils or aggregation in other amyloidogenic proteins. This is compatible with the inverse preferences of alanine to form helices and of threonine to support beta-sheet structures, which are crucial for amyloid fibrils formation. Our interest in these mutations was initiated by studying the potential effects of the A539T substitution in the butyrylcholinesterase BChE-K variant on amyloid fibrils formation in Alzheimer's disease. Other examples are, Parkinson's disease (PD), where A53T alpha-synuclein occurs in Lewy bodies and familial amyloid polyneuropathy (FAP), where an A25T substitution appears in transthyretin (TTR). In peripheral organs, an A34T substitution is found in the light chain immunoglobulin genes of patients with systemic amyloidosis and in familial hypercholesterolemia, an A370T substitution occurs in the LDLR regulator of cholesterol homeostasis. That such substitutions appear in proteins with important cellular functions suggests that they confer antagonistic pleiotropy, providing added value at an earlier age but causing damages and inducing amyloid diseases later on. This, in turn, may explain the evolutionary selection and preservation of these substitutions. The structural effect of residue substitutions and in particular A to T substitutions in amyloidogenic diseases thus merits further attention.
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PMID:Alanine-to-threonine substitutions and amyloid diseases: butyrylcholinesterase as a case study. 2006 Aug 16


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