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)

Myasthenia gravis (MG) is probably the best studied autoimmune disease caused by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction, subsequently leading to abnormal fatigability and weakness of skeletal muscle. Extraocular muscle weakness with droopy eyelids and double vision is present in about 90% of MG patients, being the initial complaint in about 50%. In approximately 20% of the patients the disease will always be confined to the extraocular muscles. The single most important diagnostic test is the detection of serum antibodies against AChR which is positive in 90% of patients with generalized MG, but only in 65% with purely ocular MG. Electromyographic studies and the Tensilon test are of diagnostic value in clear-cut cases, but may be equivocal in purely ocular myasthenia, especially the latter not rarely producing false-positive results. Treatment response to corticosteroids and anti-cholinesterase agents is satisfactory in many patients with ocular MG, however other immunosuppressive drugs may also be needed. Pathogenetically relevant steps of the underlying autoimmune process have been elucidated during the last few years; nevertheless a number of questions remain open, especially what starts off the autoimmune process, and why are eye muscles so frequently involved in MG?
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PMID:Ocular myasthenia gravis. A critical review of clinical and pathophysiological aspects. 815 54

The patient was a 79-year-old male. On CT of the chest, a mass shadow of the anterior mediastinum was found. He did not complain of symptoms, and there were no clinical signs of myasthenia gravis (MG) before surgery. The tumor and the thymus was completely resected. The pathological diagnosis was non-invasive thymoma, and his postoperative course was satisfactory. However, 2 months after the operation, the patient complained of ptosis, diplopia, dysphagia, and muscle weakness, which deteriorated rapidly. The titer of anti-acetylcholine receptor antibody was high at 91.0 nmol/l. By medication of anti-cholinesterase drug and predonin, the symptoms of MG improved. After resection of thymoma, postoperative follow-up with considering the possibility of postoperative MG is necessary.
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PMID:[A case of myasthenia gravis developing after resection of non-invasive thymoma]. 846 68

Several case reports of resistance to short-term administration of nondepolarizing neuromuscular blocking agents (NNMBAs) have been reported in research and surgical settings. Recently, several reports documented resistance to NNMBAs during therapy for prolonged paralysis in critically ill patients. Adverse outcomes associated with NNMBA resistance may include inadequate ventilatory management or suppression of patient movement, and an increased risk of dose-dependent cardiovascular adverse effects. Pharmacoeconomic issues must be considered in that the cost of NNMBA therapy in a resistant patient may be significant. Although the specific etiologies of resistance are not clear, several pharmacodynamic and pharmacokinetic alterations may occur as a consequence of disease state or concomitant drug therapy. Pharmacodynamic changes include altered acetylcholine receptor physiology or sensitivity, inhibition of serum cholinesterase activity, and interaction with plasma constituents. Alterations in distribution volume, protein binding, and clearance may also contribute to resistance in several disease states.
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PMID:Resistance to nondepolarizing neuromuscular blocking agents. 872 99

Calcitonin gene-related peptide (CGRP), a neuropeptide may play a role in the formation of neuromuscular junctions is synthesized by the motor neurons and is able to stimulate the expression of acetylcholine receptor (AChR) in cultured myotubes. By using antibody and DNA probe that are specific for acetyl cholinesterase (AChE), we reported the expression of AChE could also be stimulated by CGRP in cultured chick myotubes. After CGRP application, the amount of AChE protein, that showed a molecular weight of approximately 105 kDa as recognized by the anti-AChE monoclonal antibody, was increased by approximately 1.7-fold. Two transcripts encoding AChE, approximately 4.8 and approximately 6.0 kb, were identified and their levels of expression were increased to approximately 3-fold after treatment with CGRP. However, the total AChE enzymatic activity in the CGRP-treated myotubes was unchanged. These evidences suggest that most of the CGRP-induced AChE proteins in the cultured chick myotubes are the inactive pool of enzyme.
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PMID:Calcitonin gene-related peptide increases the expression of acetylcholinesterase in cultured chick myotubes. 891 98

A 46-year-old woman was admitted to our hospital with chest pain. Chest X-ray and CT revealed an anterior mediastinal mass as well as several small masses attached to the left chest wall. Thymoma was diagnosed by percutaneous biopsy. The serum level of anti-acetylcholine receptor antibody was 30.3 pmol/ml. At operation, the thymoma was found left in the anterior mediastinum, extending to the upper lobe of the lung. There were also numerous tumors of various size in the left parietal pleura. Thymectomy, partial resection of the upper lobe of the lung and pleurectomy were performed. One month later, she developed myasthenia gravis. After a complete remission of myasthenia gravis brought about by anti-choline esterase therapy, the patient was treated with irradiation. She has been well for more than five years after the operation but her serum anti-acetylcholine receptor antibody level is still higher than normal.
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PMID:[A case of thymoma with pleural dissemination which was treated by pleurectomy with patient survival without recurrence for more than five years]. 961 85

The effects of subchronic oral administration of metrifonate, a long-acting cholinesterase (ChE) inhibitor, on cholinergic neurotransmission were assessed in young adult male Wistar rats. Animals were treated twice daily with metrifonate. In a pilot study testing a 100 mg/kg dose of metrifonate for up to 14 days, ChE activity was found to steadily decrease to reach maximum inhibition levels of about 55%, 80% and 35% in brain, erythrocytes and plasma. Steady-state inhibition levels were attained by the 10th day of treatment. When metrifonate-treatment was discontinued, ChE activity in plasma returned to control levels within another day, while erythrocyte and brain ChE activity took more than 2 weeks to recover. In subsequent dose-response studies, metrifonate treatment was given for 3 and 4.5 weeks at doses of 0, 12.5, 25, 50, and 100 mg/kg, to different groups of animals, respectively. Correlation analysis indicted that brain ChE inhibition was more accurately reflected by erythrocyte than by plasma ChE inhibition, although all effects were highly correlated. The changes in ChE activity were not paralleled by changes in other parameters of the cholinergic neurotransmission, such as acetylcholine synthesis rate or acetylcholine receptor binding. It is therefore concluded that repeated administration of metrifonate to rats induces a long-lasting inhibition of ChE activity in a dose-related and predictable manner, which is neither subject to desensitization nor paralleled by counterregulatory downregulation of muscarinic or nicotinic receptor binding sites in brain.
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PMID:Effects of subchronic administration of metrifonate on cholinergic neurotransmission in rats. 969 Jul 34

We performed transient evoked otoacoustic emission (TEOAE) measurements on 29 ears of myasthenia gravis (MG) patients. The purpose of the study was to support the role of acetylcholine (ACh) in the efferent innervation of cochlear outer hair cells (OHCs). Another aim was to establish additional diagnostic tools for the early determination of MG. Initially, threshold audiometry and impedance measurements showed normal values on the ears examined. The main finding was that TEOAE values were significantly lower in MG patients than in healthy controls. Mestinon, a reversible cholinesterase inhibitor, resulted in a significant increase in mean values of TEOAEs, although these values were still lower than normal. The results suggest that in MG, acetylcholine receptor (AChR) autoantibodies inhibit the function of OHC AChRs. Thus, the TEOAE generated by the active movements of OHCs is decreased in MG. Mestinon prevents the degradation of ACh, and thus stimulates efferent function and increases TEOAE values. The results obtained in this study support the role of ACh in the efferent function of OHC, as well as the impaired function of hair cell AChRs in MG patients. Consequently, measuring TEOAEs may be useful in the early diagnosis of some forms of MG. These results reinforce the importance of collaboration between neurologists and otolaryngologists in the management of diseases with pathological neurotransmission.
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PMID:Otoacoustic emission in myasthenia gravis patients and the role of efferent activation. 987 40

We reported a 63-year-old woman, suffered from myasthenia gravis with thymoma who later developed subacute motor neuronopathy after thymectomy. She noticed distally dominant muscle weakness and atrophy of bilateral upper extremities without sensory loss 4 month after thymomectomy. Her muscle weakness did not improve by intravenous administration of anti-cholinesterase (Tensilon test). Electrophysiological examinations showed no decremental response of examined muscles during repetitive nerve stimulation, nor motor nerve conduction block nor demyelination of affected peripheral nerves. Laboratory study demonstrated positive anti-acetylcholine receptor, anti-nuclear and SS-A antibodies. On immunohistochemistry, the patient's sera positively stained human and rat anterior horn cell cytoplasm as well as axoplasm of spinal white matter and root nerve axon, suggesting the presence of anti-axon antibody, possibly against neurofilament or tubulin components. The biopsied muscle specimen showed neurogenic muscle changes, but with no evidence of vasculitis nor cellular infiltration. Therapeutic trial of plasmapheresis was effective for her muscle weakness. Further recovery of weakness and muscle atrophy of hand muscles was obtained by combined therapy of intravenous and oral corticosteroid administration and plasmapheresis. These clinical, electrophysiological and histological findings suggested that antibodies against neuronal component might be responsible for her motor neuronopathy associated with myasthenia gravis. The findings of our case study may support the idea that some cases of motor neuron disease are caused by auto-immune mechanism.
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PMID:[Subacute motor neuronopathy associated with myasthenia gravis and thymoma]. 1054 13

Subchronic neurotoxic effects of sarin (O-isopropyl methylphosphonofluoridate) treatment at various doses in male Sprague Dawley rats were studied. The animals were treated with a single intramuscular (im) injection of 0.01, 0.1, 0.5, or 1 x LD50 (100 microg/kg). The animals were maintained for 90 d thereafter. [3H]Hexamethonium iodide was used to monitor the changes in blood-brain barrier (BBB) permeability in cortex, brainstem, midbrain, and cerebellum. Brainstem exhibited a significant decrease (approximately 58% of control) in uptake of [3H]hexamethonium iodide at 1 x LD50 dose. No significant changes were observed in BBB permeability in cortex, midbrain, and cerebellum at any dose. Plasma butyrylcholinesterase (BChE) activity remained unchanged, reflecting recovery of the enzyme activity from the initial inhibition following single exposure of 1 x LD50 sarin. Acetylcholinesterase (AChE) activity in the cortex remained inhibited (approximately 29%), whereas in the brainstem there was an increase (approximately 20%) at 1 x LD50 dose of sarin. The m2-selective muscarinic acetylcholine receptor (m2-mAChR) ligand binding was inhibited significantly at 1 x LD50 in the cortex, whereas brainstem showed significantly increased (approximately 45%) ligand binding at 1 x LD50 dose. Nicotinic acetylcholine receptor (nAChR), on the other hand, showed a biphasic response in ligand binding in the cortex with a decrease (approximately 30%) at 0.01 x LD50 but an increase (approximately 40%) at 1 x LD5O. Brainstem did not show any significant change in nAChR ligand binding. These results suggest that single exposure of sarin could lead to changes that may play an important role in neuropathological abnormalities in the central nervous system.
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PMID:Subchronic effects following a single sarin exposure on blood-brain and blood-testes barrier permeability, acetylcholinesterase, and acetylcholine receptors in the central nervous system of rat: a dose-response study. 1113 98

Transcriptional and immunocytological characterization of thymic epithelial (TE) cell line TE750 shows that these cells, like primary TE cell cultures, transcribe alpha-3, alpha-5 and beta-4 acetylcholine receptor (AcChR) subunit genes while expressing cortical, medullary and epithelial differentiation thymic markers. Incubation of TE750 cells with nicotine decreases cell adherence and growth as measured through direct cytological observation and nucleic acid quantification, respectively. Physostigmine, a traditional cholinesterase inhibitor that also activates nicotinic AcChRs, reproduces the effects of nicotine. Strengthening the hypothesis that cholinergic receptors mediate the effects of physostigmine, acetylcholinesterase (AcChase) activity is not detected in TE750 cells. Also, like thymocytes, TE750 cells express choline acetyltransferase (ChAT), indicating that the natural transmitter AcCh can be produced locally within the thymic parenchyma. Taken together these findings indicate that TE750 cells in culture represent a suitable in vitro system for the analysis of cholinergic mechanisms operational in the thymic epithelium.
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PMID:Thymic epithelial cell line expresses transcripts encoding alpha-3, alpha-5 and beta-4 subunits of acetylcholine receptors, responds to cholinergic agents and expresses choline acetyl transferase. An in vitro system to investigate thymic cholinergic mechanisms. 1143 Oct 5


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