Study of long‐term anticholinesterase therapy

Engel, Andrew G.; Lambert, Edward H.; Santa, T

doi:10.1212/wnl.23.12.1273

Cited by 136 publications

(42 citation statements)

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“…la and b), abundant synaptic vesicles were present in the nerve terminals; junctional folds were of essentially normal height and morphology; and the synaptic clefts were of normal width over much of the nerve terminals, the clefts only occasionally containing a limited amount of debris characteristic of chronic MG (3,8,(16)(17)(18). Thus, we conclude that the significant reduction in AcCh sensitivity observed in these endplates cannot be attributed primarily to destruction and removal of junctional folds (22). More detailed analysis, however, revealed subtle alterations of a previously undescribed nature.…”

Section: Methodsmentioning

confidence: 67%

“…X200,000. (22), or, in the absence of such deformations, to determine if there were morphological alterations compatible with suggestions of immunoglobulin-like factors attached to the functional receptor complex (3). Although only one patient with early onset MG was studied, a large number of muscle bundles was obtained from the external and internal intercostal muscles, and all the endplate regions investigated disclosed the same features.…”

Section: Methodsmentioning

confidence: 99%

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Studies of human myasthenia gravis: electrophysiological and ultrastructural evidence compatible with antibody attachment to acetylcholine receptor complex.

Rash¹,

Albuquerque²,

Hudson³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

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Neuromuscular junctions from patients with early onset and chronic myasthenia gravis were examined by electrophysiological and ultrastructural techniques. Acetylcholine (AcCh) sensitivities were reduced by 34-63% in early onset myasthenia and 60-80% in chronic myasthenia. Ultrastructural analysis revealed that virtually all junctional folds of the early onset patients were intact but that the AcCh-receptor-rich crests of these folds were uniformly covered by an attached layer of 30 X 70 A particles arranged in small tufts or rosettes. In chronic myasthenic endplates, however, junctional fold crests were destroyed, apparently being replaced by vesicular membrane debris similarly labeled by tufts of 30 X 70 A particles. Thus, the initial reduction in junctional AcCh sensitivity observed in early onset myasthenia gravis may be attributed at least in part to in situ masking or inactivation of AcCh receptors, whereas the marked decrease in AcCh sensitivity observed in the chronic myasthenic patient may represent a combination of two factors: (a) in situ masking of AcCh receptors and (b) destruction of the receptor-containing crests of the junctional folds. These observations are compatible with an autoimmune etiology of myasthenia gravis initially involving an apparent antibody attachment to one or more components of the functional AcCh receptor complex, followed by systematic destruction and removal of junctional folds by both humoral and cell-mediated autoimmune responses.

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Section: Methodsmentioning

confidence: 67%

Section: Methodsmentioning

confidence: 99%

Studies of human myasthenia gravis: electrophysiological and ultrastructural evidence compatible with antibody attachment to acetylcholine receptor complex.

Rash¹,

Albuquerque²,

Hudson³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

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“…The cause may be an additional reduction in the number of endplate AChR sites as a result of disorganization of the postsynaptic muscle membrane resulting from the pyridostigmine. [20][21][22] This would further decrease the safety margin of neuromuscular transmission and thus lead to additional muscle weakness. We hypothesize that b 2 -adrenergic agonists can optimize the beneficial response to pyridostigmine by increasing stability of the muscle endplate structures and prevent the additional loss of endplate AChRs that results from chronic anticholinesterase medication.…”

Section: Case 2 (Patient 4)mentioning

confidence: 99%

Salbutamol and ephedrine in the treatment of severe AChR deficiency syndromes

et al. 2015

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Objective: To evaluate the response to salbutamol and ephedrine in the treatment of congenital myasthenic syndromes due to CHRNE mutations causing severe acetylcholine receptor (AChR) deficiency.Methods: A cohort study of 6 patients with severe AChR deficiency, symptomatic despite optimal therapy with anticholinesterase and 3,4-diaminopyridine, were analyzed for their response to the addition of salbutamol or ephedrine to their medication. Baseline quantitative myasthenia gravis (QMG) (severity) scores were worse than 15 of 39. Patients were assessed in clinic with QMG and mobility scores. Pretreatment and 6-to 8-month follow-up scores were evaluated.

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“…Muscles isolated from rats chronically treated with neostigmine have been shown to possess reduced miniature endplate potential (m.e.p.p.) amplitudes (Roberts & Thesleff, 1969;Engel et al, 1973;Ward et al, 1975) and reduced postsynaptic sensitivity to iontophoretically applied ACh . These reports have led to the suggestion that chronically elevated endplate ACh levels might reduce postsynaptic sensitivity at the neuromuscular junction.…”

Section: Introductionmentioning

confidence: 99%

The effect of chronic neostigmine treatment on channel properties at the rat skeletal neuromuscular junction

Gwilt

Wray

1986

British J Pharmacology

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1 We have studied the effects ofchronic neostigmine treatment on single channel properties at the rat skeletal neuromuscular junction. Rats received 0.86 mg kg -neostigmine (s.c.) daily for 9-11 days. Microelectrode recordings were then made from the extensor digitorum longus muscle. 2 The amplitude of miniature endplate potentials was significantly reduced in muscles from neostigmine-treated rats as compared with controls. 3 Acetylcholine (2-55 M) applied in the bath produced a depolarization and associated channel opening frequency (from voltage noise analysis) which were significantly reduced in neostigminetreated muscles with respect to controls. 4 The depolarization resulting from the opening of a single channel (from voltage noise analysis) and single channel open time and conductance (from current noise analysis) were not significantly changed by chronic neostigmine treatment. 5 It is concluded that chronic neostigmine treatment causes an adaptive reduction in the number of functional acetylcholine receptors at the endplate without otherwise affecting single channel properties themselves.

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Study of long‐term anticholinesterase therapy

Cited by 136 publications

References 0 publications

Studies of human myasthenia gravis: electrophysiological and ultrastructural evidence compatible with antibody attachment to acetylcholine receptor complex.

Studies of human myasthenia gravis: electrophysiological and ultrastructural evidence compatible with antibody attachment to acetylcholine receptor complex.

Salbutamol and ephedrine in the treatment of severe AChR deficiency syndromes

The effect of chronic neostigmine treatment on channel properties at the rat skeletal neuromuscular junction

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