Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Airway hyperreactivity is recognized as one of the long-term sequelae of bronchopulmonary dysplasia (BPD). Due to the improved care and prognosis of very low-birth weight infants, the incidence of BPD is increasing. There are data that suggest the increased survival of premature infants may be associated with the observed increased incidence of childhood asthma. The hyperoxia received as part of the treatment of respiratory distress syndrome is believed to be partly if not completely responsible for BPD. To gain insight into the potential role that hyperoxia might play in producing airway hyperreactivity, 4-day-old guinea pig pups were exposed to 70% oxygen or air for 96 h, and airway responsiveness to acetylcholine (ACh) was assessed both 2 and 9 days after the completion of the hyperoxia exposures. Unlike ozone, the mechanism for the persistently increased airway reactivity is not related either to the inhibition of neuronal acetylcholinesterase or inhibition of the neuronal M2 muscarinic receptor. A difference in antioxidant protection did not account for the increased response of the neonatal guinea pigs compared with hyperoxia-exposed rat pups. These data support the usefulness of the neonatal guinea pig as a model to study the mechanism responsible for hyperoxia-induced airway hyperreactivity.
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PMID:Airway hyperreactivity produced by short-term exposure to hyperoxia in neonatal guinea pigs. 922 25

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

The present study describes the effects of pyridostigmine (PYR; 0.2 mg/kg) and atropine sulphate (AS; 5 mg/kg) on guinea-pigs intoxicated by a high dose (2xLD50) of the organophosphate compound, soman, an irreversible inhibitor of acetylcholinesterase. The medication was shown to counteract the acute respiratory distress and lethality normally produced by the intoxication. Moreover, due to the central activity of AS, soman-induced electrocorticographic (ECoG) seizure activity was either totally prevented, or reduced in duration and overall intensity. In addition, as established in the 24-hr survivors, seizure-related neuropathology was either prevented, or reduced in topographical extent and severity. An attempt to correlate our electrographic and morphological findings gives evidence that (a), the occurrence of seizure activity is the primary factor necessary for the development of acute neuropathology; (b), the duration of ECoG seizures is a secondary factor, on which the topographical distribution of brain damage finally depends; (c), the minimal duration of seizures necessary to produce 24 hr-damage in the most sensitive areas (e.g. the amygdala) is less than 70 min; (d), the overall intensity/power of epileptiform discharges is a tertiary factor which influences the severity of damage; (e), in addition, ECoG power spectral analysis suggested that an acute increase of relative power in the lower (delta) frequency band might be a real-time external marker of the starting cerebral lesions and is thus predictive for their future installation. All these data confirm the tight relationships which exist between seizure activity and neuropathology in soman poisoning, and suggest that refined, standardized analysis of electrographic parameters drawn from ECoG tracings and power spectrum might serve as a useful tool to predict the presence, localization, and severity of soman-induced brain damage.
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PMID:Effects of atropine sulphate on seizure activity and brain damage produced by soman in guinea-pigs: ECoG correlates of neuropathology. 1102 61

A 50-year-old man swallowed 200 ml of an insecticide containing the organophosphates dimethoate and phenitrotion in an attempted suicide. On admission, signs of a cholinergic syndrome were observed: miosis, rhinorrhoea, and fasciculations. This was followed by bradycardia with hypotension and vomiting. The patient was treated with the antidotes atropine and obidoxime. Decreasing consciousness necessitated intubation, mechanical ventilation and other supportive measures. Although the serum concentrations of both organophosphate compounds rapidly decreased, the activity of cholinesterase showed a prolonged inhibition. The clinical course was complicated by hypotension, acute respiratory distress syndrome, nosocomial pneumonia, and an epileptic seizure. A period with muscle weakness and a persisting depressive disorder then followed. This case is characteristic for acute intoxications with irreversible acetylcholinesterase inhibitors, such as organophosphate compounds. The treatment of these potentially severe intoxications includes rapid decontamination and the administration of high doses of atropine followed by obidoxime. Mechanical ventilation and circulatory support are also indicated.
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PMID:[Poisoning with organophosphate compounds]. 1180 37

Ten to twenty percent of the offspring of mothers suffering from myasthenia gravis (MG) also develop transient neonatal MG, since maternal antibodies are able to cross the placenta. We report the course of two newborns of a mother with MG and a healthy father. The first pregnancy was complicated during the 3rd trimester by a hydramnion. The newborn presented with generalized muscle weakness, respiratory distress, weak sounding, anaemia, and poor sucking. Mechanical ventilation was necessary. Confirmation of the diagnosis was achieved by the result of repetitive muscle stimulation, showing a typical decrement in the EMG, and measurement of serum antiacetylcholin receptor antibodies. For 3 months, the infant was treated with neostigmin (cholinesterase inhibitor). After 26 days of hospitalization, the patient was released and followed up regularly. Myasthenic symptoms completely resolved. Side effects of the treatment were not observed. The course of the second pregnancy was normal. This second newborn was healthy. Our case report is remarkable for the very different presentation of two children of the same mother with MG during pregnancy and after delivery, with one child developing severe transient neonatal MG, initially requiring intensive care unit (ICU) treatment followed by quick recovery, and one child being healthy. We also present a score for monitoring the clinical course and adjusting anticholinesterase therapy accordingly.
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PMID:[Transient neonatal myasthenia gravis]. 1224 67

Acute intoxication by organophosphate pesticides is frequent in Morocco. We report two cases of malathion poisoning complicated by intermediate syndrome. The purpose of this work is to describe distinctive features of this syndrome, it arises 48-96 h after the cholinergic crisis and it is characterized by respiratory paresis with difficulties of weaning from the assisted respiratory, deficit of proximal limbs, neck flexors, and cranial nerves. This syndrome coincides with the prolonged inhibition of the acetylcholinesterase, and is not due to the necrosis of muscular fiber's necrosis. Both clinical and electromyographic features are explained by a combined pre- and postsynaptic dysfunction of the neuromuscular transmission. The difficulty of this syndrome lies in its rarity and also its severity, because of the respiratory failure, which justifies medical supervision in intensive care unit, for at least 96 h, in expectation for the respiratory distress, all the more cholinergic syndrome is intense.
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PMID:[The intermediate syndrome during organophosphorus pesticide poisoning]. 1512 Jul 79

Amongst organophosphate compounds, both pesticides and warfare neurotoxics are probably the most representative. These compounds are irreversible acetylcholinesterase inhibitors. Usual clinical signs observed after acute poisoning are mainly respiratory distress, convulsions and seizures. Following acute poisoning, an emergency treatment must be provided as soon as possible (maximum delay of 1 hour post-poisoning), to prevent irreversible brain damage and patient death. At the present time, there is no efficient delayed treatment which could be provided if this 1 hour latency is overpassed. However, neurogenesis by stem cell engraftment, eventually complemented by gene therapy strategy, could be a potential therapeutic approach to repair organophosphate-induced brain damage. Main stem cell engraftement strategies successfully used for brain damage of various origins are reviewed in this Article.
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PMID:[Stem-cell engraftment as delayed therapy to repair organophosphate-induced brain damage]. 1524 43

Exposure to a chemical warfare nerve agent (CWNA) leads to severe respiratory distress, respiratory failure, or death if not treated. We investigated the toxic effects of nerve agent VX on the respiratory dynamics of guinea pigs following exposure to 90.4 mug/m3 of VX or saline by microinstillation inhalation technology for 10 min. Respiratory parameters were monitored by whole-body barometric plethysmography at 4, 24, and 48 h, 7 d, 18 d, and 4 wk after VX exposure. VX-exposed animals showed a significant decrease in the respiratory frequency (RF) at 24 and 48 h of recovery (p value .0329 and .0142, respectively) compared to the saline control. The tidal volume (TV) slightly increased in VX exposed animals at 24 and significantly at 48 h (p = .02) postexposure. Minute ventilation (MV) increased slightly at 4 h but was reduced at 24 h and remained unchanged at 48 h. Animals exposed to VX also showed an increase in expiratory (Te) and relaxation time (RT) at 24 and 48 h and a small reduction in inspiratory time (Ti) at 24 h. A significant increase in end expiratory pause (EEP) was observed at 48 h after VX exposure (p = .049). The pseudo lung resistance (Penh) was significantly increased at 4 h after VX exposure and remained slightly high even at 48 h. Time-course studies reveal that most of the altered respiratory dynamics returned to normal at 7 d after VX exposure except for EEP, which was high at 7 d and returned to normal at 18 d postexposure. After 1 mo, all the monitored respiratory parameters were within normal ranges. Bronchoalveolar lavage (BAL) 1 mo after exposure showed virtually no difference in protein levels, cholinesterase levels, cell number, and cell death in the exposed and control animals. These results indicate that sublethal concentrations of VX induce changes in respiratory dynamics and functions that over time return to normal levels.
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PMID:Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs. 1736 32


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