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)

The acute aspects of organophosphate poisoning are well understood. Persistent weakness and muscular wasting in some cases have been attributed to neuropathic effects resulting in muscular atrophy from denervation. Recently, necrosis of skeletal muscle has been induced by chronic inhibition of cholinesterase with organic phosphates in a reproducible experimental model. The literature on organophosphate poisoning in man alludes to cases in which it appears plausible to postulate this mechanism as a cause of a residual myopathy. A new case in which chronic organophosphate intoxication may be implicated in the etiology of a proximal myopathy is presented. Reports of additional cases, followed up from the onset of symptoms, are needed to determine whether primary myopathic effects are a clinically significant complication of chronic organophosphate poisoning.
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PMID:Myopathy of chronic organophosphate poisoning: a clinical entity? 44 67

Serum acetylcholinesterase (AChE) and pseudocholinesterase (ChE) activity in infantile and juvenile spinal muscular atrophy (SMA) was determined. The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA). In the majority of SMA Type 1 cases (6/7 tested) an absence of the asymmetric A12 form was found. This was accompanied by changes in the other asymmetric and globular forms. The latter was, however, not specific for SMA Type 1 cases. The ChE activity was increased in the majority of SMA cases as well as disease controls. The asymmetric A12 ChE form was increased in all SMA Type 3 cases, the values of this form in SMA Type 1 was variable. A change in the ChE globular forms in SMA Type 1 and SMA Type 2 was a frequent finding. It is suggested that the absence of the asymmetric A12 AChE form in SMA Type 1 arises because of muscle cell immaturity and undeveloped muscle-nerve interactions. The reason of ChE changes is obscure.
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PMID:Serum cholinesterase activity in infantile and juvenile spinal muscular atrophy. 280 Oct 18

The sensitivity of the mouse to organophosphorus-induced delayed neurotoxicity (OPIDN) has been investigated. One group of five mice received two single 1000-mg/kg po doses of tri-o-cresyl phosphate (TOCP) at a 21-day interval (on Days 1 and 21 of the study); a second group of five mice was given 225 mg/kg of TOCP daily for 270 days. A third group of five animals served as an untreated control. All animals were killed 270 days after the start of the experiment. Daily po dosing of 225 mg/kg TOCP caused a decrease in body weight gain, muscle wasting, weakness, and ataxia which progressed to severe hindlimb paralysis at termination. On the other hand, po administration of two single 1000-mg/kg doses of TOCP at a 21-day interval produced no observable adverse effects. Brain acetylcholinesterase (AChE) and neurotoxic esterase (NTE) activity were 35 and 10% of the control, respectively, in daily dosed animals while AChE and NTE in mice receiving two single 1000-mg/kg doses of TOCP were not significantly altered from the control group. Plasma butyrylcholinesterase activity was 12% of the control group in daily dosed animals. Hepatic microsomal enzyme activities of aniline hydroxylase and p-chloro-N-methylaniline demethylase and NADPH-cytochrome P-450 content in daily dosed animals were increased (141 to 161% of the control group) when compared to controls and mice receiving two single 1000-mg/kg doses of TOCP; the latter being not significantly different from each other. Degeneration of the axon and myelin of the spinal cord and sciatic fascicle were observed and were consistent with OPIDN. This study demonstrates that chronic dosing of TOCP produces OPIDN and induces hepatic microsomal enzyme activity in mice. It is concluded that while the mouse is susceptible to OPIDN, it is a less sensitive and a less appropriate test animal for studying this effect when compared to the adult hen.
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PMID:Characterization of delayed neurotoxicity in the mouse following chronic oral administration of tri-o-cresyl phosphate. 404 9

In 13 Smooth Fox Terriers with a congenital form of myasthenia gravis, clinical signs included intermittent, progressive muscle weakness that became more pronounced with exercise; muscle wasting; megaesophagus; and aspiration pneumonia. Neurologic abnormalities were apparent only during periods of weakness and included inability to retract the fore- and hindlimbs from painful stimuli. A decrement of the compound muscle action potential was evident during repetitive supramaximal nerve stimulation. Intravenous injection of a short-acting cholinesterase inhibitor evoked immediate improvement of clinical and electromyographic signs. Intracellular microelectrode studies of a biopsied external intercostal muscle revealed reduced amplitude of miniature end-plate potentials, as occurs in acquired myasthenia gravis. However, in contrast to acquired myasthenia gravis, antibodies directed against acetylcholine receptors were not demonstrable in serum and were not bound to acetylcholine receptors in muscle. Despite lack of complexing with immunoglobulin, the amount of acetylcholine receptor protein in biopsied external intercostal muscles from 9 affected pups was less than 25% of the amount in 5 unaffected littermates. The latter finding accounted for the reduction in amplitude of miniature end-plate potential and the failure of neuromuscular transmission. Treatment with a long-acting cholinesterase inhibitor in 6 cases resulted in temporary improvement in muscle strength.
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PMID:Congenital myasthenia gravis in 13 smooth fox terriers. 684 Dec 51

We describe two brothers with early onset cerebellar ataxia associated with hypoalbuminemia (EOCAH). Choreo-athetoid movements preceded the cerebellar ataxia, and serum pseudocholinesterase elevation preceded the hypoalbuminemia. The parents are first cousins. Patient 1, the 22-year-old elder brother, developed choreoathetoid movements of the neck and extremities at the age of eighteen months. He later developed slowly progressive cerebellar ataxia with decreased tendon reflexes. The choreoathetoid movements ceased at about 16 years of age. A recent examination revealed cerebellar ataxia, action myoclonus of the neck and upper limbs, diminished tendon reflexes, mild sensory disturbance in the lower extremities, and very slight amyotrophy of the feet. Patient 2, the 18-year-old younger brother, developed choreo-athetoid movements at the age of 6 years, followed by slowly progressive cerebellar ataxia with disminished tendon reflexes. No scoliosis, ECG abnormalities, or edema was detected. Serum biochemistry studies revealed elevated pseudocholinesterase (6,226 to 2,390 IU) in the patient's early teens. Serum albumin levels tended to be low (3.7 to 4.1 g/dl). Serum triglyceride and beta-lipoprotein levels were elevated in the patients' late teens. Genetic studies showed slight linkage of D9S15. The maximum lod score was 0.289 (recombination fraction rate was 0.14).
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PMID:[Familial early onset cerebellar ataxia with hypoalbuminemia]. 766 33

Distal spinal muscular atrophy is a rare lower motor neuron disorder that may be difficult to distinguish clinically from type II Charcot-Marie-Tooth disease. We report on clinical and pathologic findings in 13 members of a four-generation extended family with autosomal dominant distal spinal muscular atrophy. The patients developed a slowly progressive lower motor neuron disorder involving mainly the distal lower extremities; onset was from the second to fourth decades. Electromyography and muscle biopsy findings were indicative of motor denervation. Combined silver/cholinesterase/immunocytochemical staining of intramuscular nerve revealed abundant collateral axonal branching in mild disease but marked loss of terminal motor endplate innervation in the more severe state, suggesting decreased growth of motor axon collaterals with disease progression. Multipoint DNA linkage analysis showed that this family's disorder is not linked to the chromosome 5q11.2-13.3 spinal muscular atrophy locus.
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PMID:Autosomal dominant distal spinal muscular atrophy in four generations. 772 57

With respect to neuromuscular function, aldosterone activity, enzymatic and potassium (K) metabolism of organ tissues were investigated during the stress and adaptation stabilized phases of hypodynamically stressed rats. During adaptation, muscle tissue enzymes, such as aldolase, showed no change until the 35th day. The decrease of succinic dehydrogenase (SDH) was evident at 7 days. Lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) serum levels increased transiently on the 18th day; this implied the development of muscular atrophy. A decrease in the 42K uptake of muscle was found from the 18th day onward. In the brain, a progressive decrease of aldolase was observed. 42K uptake showed no change in the brain, but the K content increased at both 7 and 18 days of exposure. The increase of cholinesterase (ChE) was more remarkable in the brain than in muscle, although transient. We suggest that the brain plays an important part in the adaptation process, through increasing or maintaining the functions of the neuromuscular excitation system during the 7-18 days of hypodynamic exposure.
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PMID:Changes in enzymes and potassium content of the neuromuscular systems of albino rats during prolonged exposure to simulated hypogravics. 1200 7

Myasthenia gravis (MG) is a chronic neuromuscular disease which leads to varying degrees of weakness in the skeletal muscles. Some of the symptoms of the disorder include weakness of the eye muscles, difficulty in swallowing and slurred speech. When only the muscles of the eyes are affected, the illness is termed ocular myasthenia, which is often characterized by abrupt onset of diplopia and ptosis of the eyelid. In most patients with ocular-onset MG, there is a progression to involvement of other muscle groups within the first two years (generalized myasthenia). In the case reported here, a 39-year-old male of Ecuadorian descent complained of difficulty seeing, double vision, dizziness, unsteady gait, difficulty maintaining balance and fatigue for the previous two days. Neurological examination was remarkable for total external ophthalmoplegia. There was no external bulbar muscle paralysis, motor weakness, muscle wasting, sensory deficits or sphincter dysfunction. His laboratory workup was significant for elevated acetylcholine receptor antibody. He was diagnosed with ocular MG after differential diagnoses were ruled out based on the onset and presentation of symptoms, the patient's age and a normal magnetic resonance imaging exam. No signs of generalized myasthenia were detected. His symptoms improved dramatically after treatment with Acetyl cholinesterase (AchE) inhibitors and steroids, regaining much of his ocular mobility and ability to walk without gait imbalance. At follow-up visits, the patient remained healthy with no evidence development of other myasthenic signs. This case is atypical since ocular MG does not normally occur in the absence of other myasthenic forms.
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PMID:An atypical course of myasthenia gravis. 1860 52