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)

Carbaryl, a carbamate insecticide, exerts its toxic effect in animals by inhibiting the activity of neural acetylcholinesterase. Differences in sensitivity of this enzyme to inhibition were studied after intraperitoneal administration to chickens and rats. A dose of 900 mg/kg to chickens and 70 mg/kg to rats caused equivalent inhibition of brain cholinesterase activities (57% +/- 6 and 47% +/- 4, respectively) 60 min after administration, which was the time of maximal cholinergic signs. Signs of toxicity (salivation, respiratory distress, muscle tremors and weakness) were more pronounced in rats than in chickens when brain acetylcholinesterase was inhibited to the same extent in both species. Carboxylesterase activities in brain, liver, and plasma were also inhibited 60 min after administration of carbaryl to chickens and rats. Activities of enzymes associated with hepatic microsomes were unaffected. Specific activities of brain esterases, including acetylcholinesterase, carboxylesterase and neurotoxic esterase, were higher in untreated chickens than in untreated rats. Specific activities of liver esterases (carboxylesterase, A-esterase) were, however, 4- and 10-fold lower in untreated chickens than in untreated rats. Total clearance of carbaryl in the chicken, determined after intravenous administration of 5 mg/kg, was 0.26 +/- 0.02 l/kg/min. This value is 5.7 times higher than that reported for the rat, indicating that the relatively lower activities of esterases in the liver of chickens did not affect the clearance of this chemical in the avian species.
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PMID:Toxicity and toxicokinetics of carbaryl in chickens and rats: a comparative study. 150 71

A 46-year-old man after an accidental exposure to organophosphates developed florid adult respiratory distress syndrome (ARDS). A markedly suppressed level of pseudocholinesterase and red blood cell cholinesterase with profuse salivation and sweating confirmed the diagnosis of organophosphate poisoning. Within 48 hours, patient developed respiratory distress needing intubation. Despite maximum ventilatory support and positive end-expiratory pressure, hypoxia persisted, Swan Ganz (Baxter Healthcare Inc, Irvine, CA) pressures showed low pulmonary capillary wedge pressure and patient died on the third hospital day. An autopsy confirmed the picture of ARDS. Other potential causes of ARDS were excluded. Although rare, organophosphate poisoning should be added to the list of toxins causing ARDS.
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PMID:Adult respiratory distress syndrome from organophosphate poisoning. 198 45

Soman, an organophosphorous irreversible inhibitor of acetylcholinesterase, was studied for its effect on the rat blood-brain barrier (BBB) during the first 24 h of intoxication. Young adult male Sprague-Dawley rats, injected with Evans blue-dye and surviving a subsequent single convulsive dose of soman (114 micrograms/kg, 0.9LD50), presented focal and diffuse penetration of dye in areas of brain normally considered protected by the BBB. Invasion was widest during the first hour when signs of excitation, respiratory distress and convulsions peaked and was absent at 24 h. During this time period, cholinesterase inhibition, as measured by enzyme assay, persisted in brain and blood at 10% and 6% of control values respectively. Brains of nonconvulsing animals and animals pretreated with nembutal (45 mg/kg, I.P.) or with diazepam (10 mg/kg, I.P.) were free of extravasated dye. A ranking of dye-breached brain areas suggested that cerebellar and cerebral cortex were most frequently involved while brain stem was rarely stained. Ultrastructural analysis of breached areas with horseradish peroxidase as a tracer molecule, revealed that the probable subcellular mechanism of the induced breach was enhanced vesicular transport, a mechanism similarly described for seizure. Consequences of the breach were emphasized with the detection of significantly elevated levels of an exogenously administered quaternary compound, 3H-hexamethonium. These findings present additional evidence that an anticholinesterase-induced breach of the rat blood-brain barrier is convulsive dependent, demonstrates BBB mechanisms similar to that of seizure, and can allow CNS penetration of blood-borne drugs and circulatory proteins that normally would be slowed or excluded by an intact BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of an anticholinesterase compound on the ultrastructure and function of the rat blood-brain barrier: a review and experiment. 207 Mar 59

Organophosphates are the most common group of chemicals involved in poisoning in Sri Lanka. Usually, poisoning is by ingestion for suicidal purposes, although accidental poisoning is not uncommon. Poisoning due to absorption through intact or damaged skin is rare. A 32-year-old man was admitted to a peripheral hospital following assault with a 100-ml bottle of insecticide called Monocrotophos, an organophosphate. He had a 2-in. long laceration just above his left eyebrow and there was spilling of the liquid contained in the bottle over his head and face. The liquid was wiped off but the head or face was not washed. After about 3 h the patient developed symptoms and signs of early organophosphate poisoning which were treated with atropine and pralidoxime. On the 3rd day, while on therapy, the patient developed severe weakness of limbs and respiratory distress needing intubation and assisted ventilation. The patient was transferred to the neurology intensive care unit of the General Hospital, Colombo, on the eighth day. His serum potassium levels were low and an ECG showed prominent U waves in all leads. The plasma cholinesterase levels were within 37.5-50% of normal even on the 20th day indicating severe exposure.
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PMID:Respiratory failure from severe organophosphate toxicity due to absorption through the skin. 335 Apr 49

F344/N rats and B6C3F1 mice were exposed to 0, 1, 3, or 6 ppm methyl isocyanate by inhalation for 6 hr on 4 consecutive days. Deaths of rats were observed following 3 ppm exposures, and mice died after exposures to 6 ppm. Deaths appeared to be related to severe respiratory distress. Survivors in high dose groups lost weight initially, then gained weight at rates equal to controls throughout a 91-day recovery period. Lung weights increased significantly in male and female rats exposed to 3 ppm, but no persistent changes in brain, kidney, thymus, spleen, liver, or testis weights were seen in either mice or rats. Blood and serum from male and female rats were taken for clinical pathology and hematology assessments on day 7 of postexposure, the day prior to the first observed deaths of these animals. No changes or only slight changes were seen in measures of serum alanine aminotransferase, sorbitol dehydrogenase, alkaline phosphatase, or in blood and brain cholinesterase activities. However, serum creatine kinase increased with dose in both males and females. Blood urea nitrogen, creatinine, and methemoglobin were unchanged. No changes were seen in counts of red blood cells or platelets, or in red cell indices. Hemoglobin concentrations and hematocrits were slightly elevated. No changes were noted in absolute leukocyte counts, but counts of segmented neutrophils increased and lymphocytes decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The toxicity of inhaled methyl isocyanate in F344/N rats and B6C3F1 mice. II. Repeated exposure and recovery studies. 362 27

Male and female F344/N rats and B6C3F1 mice were exposed to lethal and sublethal concentrations of methyl isocyanate by inhalation. Mortality, clinical signs, body and organ weights, and changes in clinical pathology and hematology were monitored immediately after 2-hr exposures and during the ensuing 3 months. Additional studies investigated the possible involvement of cyanide in the toxicity of methyl isocyanate. During exposures, signs of restlessness, lacrimation, and a reddish discharge from the nose and mouth were evident in rats and mice. Following exposures, rats and mice were dyspneic and weak. Deaths of rats and mice exposed to lethal concentrations (20 to 30 ppm) began within 15-18 hr, with males more prone to early death than females. A second wave of deaths occurred after 8 to 10 days, affecting primarily female rats and mice exposed to 20 to 30 ppm of methyl isocyanate, and male and female rats exposed to 10 ppm. Most deaths occurred during the first month following the exposures and were preceded by periods of severe respiratory distress. Body weights decreased in proportion to dose early, but then weight gain resumed in survivors at control rates. The only organ with a consistent, dose-related weight change was the lung, which was heavier throughout the studies in animals exposed to high concentrations of methyl isocyanate. No significant clinical pathology, or hematologic changes were observed in exposed rats. Blood and brain cholinesterase were not inhibited. Studies attempting to measure cyanide in the blood of methyl isocyanate-exposed rats, and attempting to affect lethality with a cyanide antidote (sodium nitrite and sodium thiosulfate) gave negative results.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicity of inhaled methyl isocyanate in F344/N rats and B6C3F1 mice. I. Acute exposure and recovery studies. 362 44

Clinical and pulmonary function changes induced by intravenous dichlorvos (2,2-dichlorvinyldimethyl phosphate) (DDVP) toxicosis, and reversibility of these changes after atropine treatment were investigated in six Friesian calves one to three months old. From one minute after dosage, all animals showed severe respiratory distress, excitation, weakness, muscle fasciculation and cholinesterase inhibition. Decrease in dynamic lung compliance and arterial oxygen tension and increase in total pulmonary resistance, viscous work of breathing and alveolar arterial oxygen gradient were highly significant (P less than 0.01). On the other hand, body secretions, heart rate, respiratory rate, tidal volume and arterial carbon dioxide tension were not significantly affected by DDVP injection. Atropine promptly and completely reversed these changes, except for muscle fasciculations, central depression and cholinesterase inhibition which disappeared progressively within 24 hours.
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PMID:Pulmonary function changes induced by experimental dichlorvos toxicosis in calves. 373 27

Two children, now 5 1/2 and 6 years of age, presented as neonates with hypotonia, multiple joint contractures, ptosis, extraocular weakness, bulbar symptoms, and respiratory distress. Fluctuations and episodic exacerbations of weakness necessitated respiratory support. Both children are developmentally delayed and cannot walk independently, although one child underwent bilateral tenotomies. Biochemical investigations and electromyography, including slow-rate, repetitive nerve stimulation, were normal. Acetylcholine receptor antibodies in serum were absent. Single-fiber electromyography with axonal stimulation revealed prolonged mean jitter in the tibialis anterior and extensor digitorum muscles, with more than 2 abnormal individual jitter values in each muscle. Muscle biopsy demonstrated normal pattern and morphology of muscle fibers; immunohistochemical staining for cholinesterase was positive. Electron microscopy revealed abnormalities in motor endplates: atrophy, flattening of primary synaptic clefts, and paucity of side branches. These findings represent one of the postsynaptic abnormalities (i.e., acetylcholine receptor deficiency or paucity of synaptic folds). Both children improved clinically on pyridostigmine therapy. Arthrogryposis congenital multiplex due to congenital myasthenic syndrome, as diagnosed in our patients, has been reported once before. The diagnosis can be established by clinical history, neurologic examination, and electrophysiologic and pathologic findings. Clinical improvement can be achieved with high-dose anticholinesterase therapy.
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PMID:Arthrogryposis multiplex congenita due to congenital myasthenic syndrome. 761 91

Carbofuran is a carbamate that functions as a cholinesterase inhibitor. Accidental or intentional ingestion can produce a life-threatening syndrome that requires prompt diagnosis and treatment. We describe a case of intentional carbofuran ingestion that resulted in coma, respiratory failure from acute respiratory distress syndrome (ARDS), and cortical blindness.
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PMID:Human sequelae of severe carbamate poisoning. 952 4

Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and incapacitation. Here, as in a recent review it is stated that other therapeutic approaches may improve protection. Former studies on the "direct effects" of oximes led to the conclusion that drug-induced inhibition of acetylcholine (ACh)-release shortly (1 min) after the acute OP-intoxication, could prevent and counteract convulsions and improve survival. In general, the accumulation of ACh in the synaptic cleft is considered to be responsible for the symptoms that ultimately lead to death. Therefore, prevention or suppression of this excessive accumulation of ACh could be a generic approach to antagonize OP-poisoning. Preliminary evidence for this concept has been put forward. Evaluation of drugs that would be able to prevent and counteract ACh accumulation, led to the conclusion that adenosine receptor agonists could be promising candidates. Pilot experiments demonstrated that intramuscular administration of the adenosine receptor agonists NECA (5'-N-ethylcarboxamido-adenosine) or CPA (N6-cyclopentyl adenosine) 1 min following a subcutaneous soman poisoning (1.5-2LD50) in rats, resulted in (1) prevention or postponement of chewing, salivation, convulsive activity, and respiratory distress (cholinergic symptoms), (2) improvement of survival rate (24 h), (3) a low level of extracellular brain ACh, as opposed to high levels of extracellular brain ACh in untreated animals. It is concluded that (1) adenosine agonists protect acutely soman-poisoned rats without the need of additional treatment with atropine, oxime or diazepam, (2) prevention of ACh accumulation in this way may be a new generic approach in the treatment of OP-poisoning.
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PMID:New generic approach to the treatment of organophosphate poisoning: adenosine receptor mediated inhibition of ACh-release. 1002 9


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