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)

Myasthenia gravis (MG) is mediated by circulating antibodies directed against acetylcholine receptor (AChR) but the antibody titre is poorly correlated with the clinical severity of the disease. We analysed acetylcholinesterase (AChE) activity, molecular forms and distribution during in vitro synaptogenesis, in the presence of sera from MG patient. We observed that the formation of AChE patches is inhibited in proportion to the anti-AChR antibody titre, whatever the clinical severity of the disease. The total activity and the proportion of the different molecular forms were unchanged suggesting that AChE level and distribution are controlled by independent mechanisms. To clarify the relationship between the mechanisms of AChE concentration during synaptogenesis and AChR concentration, we compared the effect of MG sera (receptors are internalised and degraded) and of the acetylcholine antagonist alpha-bungarotoxin (non-functional receptors are still present in the muscular membrane). In the presence of alpha-bungarotoxin, the number of AChR clusters, and AChE activity and concentration were equivalent to control values. The comparison of the results obtained with antibodies and alpha-bungarotoxin suggests that the presence and/or concentration of AChR is a necessary condition for normal concentration of AChE during synaptogenesis.
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PMID:Effect of sera from myasthenia gravis patients and of alpha-bungarotoxin on acetylcholinesterase during in vitro neuromuscular synaptogenesis. 841 74

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

A 52-year-old woman had a 14-year history of stridor attacks. Pulmonary function tests revealed reversible airway obstruction, and bronchial asthma was diagnosed. She also has bilateral ptosis, diplopia, and moderate weakness of all four limbs; a positive edrophonium test confirmed the diagnosis of myasthenia gravis. Although the parasympathetic system plays an important role in the regulation of bronchial tone, in this patient the edrophonium test did not provoke an asthmatic attack or exacerbate pulmonary function, except for increases in sputum production and in frequency of cough. The general weakness was usually worse in the afternoon. The decrease in grip strength and the shortening of arm elevation time also occurred after asthma attacks, which means that general muscle fatigue was caused by the work of breathing. Furthermore, dyspnea increased and pulmonary function worsened when an anti-cholinesterase inhibitor was discontinued, probably because of respiratory muscle weakness. Accordingly, the clinical status of bronchial asthma seemed to change in parallel with that of the myasthenia gravis.
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PMID:[Bronchial asthma complicated by myasthenia gravis]. 869 67

Cholinesterase inhibitors are still important in the treatment of myasthenic patients. Therapeutic principles, indications and adverse effects are discussed in detail. Methods of pharmacological monitoring had been searched over many years. Besides determination of pyridostigmine plasma concentration, erythrocyte-bound acetylcholinesterase (AChE) activity could provide a possibility to monitor therapy with cholinesterase inhibitors. 88 patients with myasthenia gravis were investigated. The results demonstrated that after pyridostigmine erythrocyte-bound as well as synaptic AChE is inhibited. Moreover, erythrocyte-bound AChE has proven to be a parameter of cholinesterase inhibitor effect. After injection of edrophonium-chloride (Tensilon) inhibition of AChE activity can be demonstrated as well. During steady pyridostigmine doses stable plasma concentrations and AChE inhibition depend on the respective dosage. Higher daily doses result in greater stability of pharmacologic parameters, whereas low daily doses lead to great interindividual differences of AChE inhibition even after equal pyridostigmine doses. Intraindividually there is no strong correlation, too. Therefore estimation of erythrocyte-bound AChE activity is not useful for routine pharmacological monitoring of cholinesterase inhibitor therapy, but may be helpful in some clinical conditions. The method provides some advantages over pyridostigmine plasma concentration, since it is applicable for other cholinesterase inhibitors, too, and since it requires less technical equipment and time.
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PMID:[Therapy of myasthenia gravis with cholinesterase inhibitors--principles and pharmacologic monitoring]. 890 Aug 91

Pyridostigmine, a carbamate acetylcholinesterase (AChE) inhibitor, is routinely employed in the treatment of the autoimmune disease myasthenia gravis. Pyridostigmine is also recommended by most Western armies for use as pretreatment under threat of chemical warfare, because of its protective effect against organophosphate poisoning. Because of this drug's quaternary ammonium group, which prevents its penetration through the blood-brain barrier, the symptoms associated with its routine use primarily reflect perturbations in peripheral nervous system functions. Unexpectedly, under a similar regimen, pyridostigmine administration during the Persian Gulf War resulted in a greater than threefold increase in the frequency of reported central nervous system symptoms. This increase was not due to enhanced absorption (or decreased elimination) of the drug, because the inhibition efficacy of serum butyryl-cholinesterase was not modified. Because previous animal studies have shown stress-induced disruption of the blood-brain barrier, an alternative possibility was that the stress situation associated with war allowed pyridostigmine penetration into the brain. Here we report that after mice were subjected to a forced swim protocol (shown previously to simulate stress), an increase in blood-brain barrier permeability reduced the pyridostigmine dose required to inhibit mouse brain AChE activity by 50% to less than 1/100th of the usual dose. Under these conditions, peripherally administered pyridostigmine increased the brain levels of c-fos oncogene and AChE mRNAs. Moreover, in vitro exposure to pyridostigmine increased both electrical excitability and c-fos mRNA levels in brain slices, demonstrating that the observed changes could be directly induced by pyridostigmine. These findings suggest that peripherally acting drugs administered under stress may reach the brain and affect centrally controlled functions.
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PMID:Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response. 909 57

A 34-year-old woman was admitted to our hospital because of ptosis, dysarthria, muscle weakness of upper limbs and skin lesions. At the age of 22 years, she was diagnosed as having systemic lupus erythematosus (SLE) due to the presence of arthritis and high titer of antinuclear antibody. On admission, the high antiacetylcholine receptor antibody titer, along with the positive tensilon test and electromyography established a diagnosis of myasthenia gravis (MG). The demonstration of anti-intercellular antibodies both in cutaneous tissue and blood confirmed the diagnosis of pemphigus. MRI showed hypertrophic thymus. After thymectomy, the myasthenic symptoms aggravated and SLE and pemphigus erythematosus relapsed despite anti-cholinesterase treatment with plasmapheresis. She was then placed on corticosteroid therapy with an improvement of her all symptoms. This very rare case of MG associated with SLE and pemphigus erythematosus suggests that these diseases share common immunological abnormalities.
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PMID:[A case of myasthenia gravis associated with systemic lupus erythematosus and pemphigus erythematosus]. 916 41

Pyridostigmine bromide (PB) is a reversible cholinesterase inhibitor used routinely in the treatment of myasthenia gravis and recently by the US Army as a prophylactic agent against potential nerve gas attack in the Persian Gulf War. Pyridostigmine has been implicated as one of several possible causative factors associated with Persian Gulf illnesses. To investigate toxic interactions between PB and other drugs, male ICR mice received contralateral ip injections of either a selected adrenergic drug or caffeine, followed 15 min later by PB. Representative isobolograms plotted for each drug interaction illustrate that a beta-adrenoceptor agonist (isoproterenol), selective beta 2-adrenoceptor agonists (salbutamol, terbutaline), alpha 1- and alpha 2-adrenoceptor antagonists (yohimbine, phentolamine, prazosin), as well as the stimulant caffeine, strongly potentiate the lethal effect of PB. Agents with agonist activity at both alpha- and beta-adrenoceptors (epinephrine, norepinephrine) additively increase PB-induced lethality. The potentiation of toxicity between PB and these agents was counteracted by pretreatment with atropine and atropine methyl nitrate. An alpha 2-adrenoceptor agonist (clonidine) and beta-adrenoceptor antagonists (propranolol, nadolol, acebutolol) did not increase PB-induced lethalities. These data demonstrate a toxic synergism between PB, several commonly used classes of adrenergic agents and caffeine when exposure occurs in different combinations. Future studies into the mechanism(s) of these interactions may bring into question the usage of PB as a protective agent in combat conditions as well as delineate any possible contributions of the drug to Persian Gulf illnesses.
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PMID:Potentiation of pyridostigmine bromide toxicity in mice by selected adrenergic agents and caffeine. 925 Nov 70

Randomised and controlled treatment studies of juvenile-onset myasthenia gravis have not been published. We therefore report our retrospective analysis of 79 patients with juvenile-onset myasthenia gravis observed for as long as 30 years. The mean age at onset was 13.7 years and median follow-up 7.7 years. The initial presentation was generalised disease in 90% and ocular disease in the remaining patients. Sixty-five patients (82%) were thymectomised. In 14 of these, treatment consisted of a combination of azathioprine (2-3 mg/kg), corticosteroids (prednisolone up to 60 mg for a maximum duration of 12 months with subsequent tapering) and acetylcholinesterase (AChE) inhibitors, and of azathioprine and AChE inhibitors in 27 patients. One patient received azathioprine and 22 AChE inhibitors only; in another no further medication was necessary. In the severely affected group (n = 16), plasmapheresis was performed additionally before thymectomy and continued for some time after the operation. Treatment was started between 1 and 14 months (mean 2.4 months) after the onset of myasthenic symptoms. No thymectomy was done in 14 patients, and immunosuppressive treatment and AChE inhibitors were given in 9 of these cases. One patient received azathioprine only; 4 patients received AChE inhibitors only. The histology of the thymus gland showed follicular hyperplasia in 89% of the 65 thymectomised patients and normal findings in the remainder. Remission occurred in 60% of patients who underwent thymectomy and in 29% of those who were not thymectomised. Hyperthyroidism (6 patients, 8%), diabetes mellitus (2 patients, 3%) and rheumatoid arthritis (2 patients, 3%) were the most frequent associated immune-mediated diseases. Epileptic seizures and neoplasia were coincident diseases in 2 (3%) and 3 (4%) patients, respectively. There were no deaths from thymectomy or from immunosupression. This open, retrospective analysis suggests that juvenile-onset myasthenia gravis can be treated satisfactorily in most patients by the use of thymectomy and/or immunosupressive medication.
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PMID:Outcome in juvenile-onset myasthenia gravis: a retrospective study with long-term follow-up of 79 patients. 930 59

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

Neuromuscular disorders can impose significant disability in patients by virtue of weakness, pain, and sensory and autonomic symptoms and deficits. For all of these disorders, supportive measures, appropriate physical therapy, and respiratory support are beneficial. Pain management can be accomplished by the use of antiepileptic medications, such as carbamazepine, phenytoin, valproic, and gabapentin. Tricyclic antidepressants can also be helpful for pain management and depression. Benzodiazepines and baclofen are helpful for management of spasticity. No specific treatment exists yet for the motor neuron disorders. In peripheral neuropathies, identifying and treating the cause is most important. In other neuropathies, such as in acute or chronic inflammatory demyelinating neuropathies, immunosuppression is indicated. Myasthenia gravis can be treated with cholinesterase inhibitors and immunosuppression. A specific treatment does not exist yet for muscular dystrophies. Immunosuppression is helpful in patients with inflammatory myopathies. Toxic myopathies can be treated by removing the causative agent and by supportive measures. Endocrine myopathies will respond to treatment of the primary endocrinopathy.
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PMID:Diagnostic algorithms for neuromuscular diseases. 992 72


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