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 an autoimmune disease of neuromuscular transmission associated with the presence of anti-acetylcholine receptor antibodies (anti-AChR Ab). Current treatment of MG includes anti-cholinesterase drugs, thymectomy, corticosteroids, immunosuppressants and plasma exchange (PE). The use of intravenous immune globulin (IVIG) in MG was proposed 10 years ago. Published results of IVIG treatment are discussed and the need for a controlled study is emphasized.
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PMID:Intravenous immune globulin in myasthenia gravis. 803 35

We describe the successful use of the short-acting, non-depolarizing neuromuscular blocking agent, mivacurium, in a patient with myasthenia gravis taking pyridostigmine 120 mg four times daily. Increased sensitivity to mivacurium was demonstrated using train-of-four monitoring. A dose of 0.5 times the recommended ED95 (3.0 mg) resulted in 93% block of T1. Spontaneous recovery was prolonged with a recovery index (25%-75% T1) of 20.5 min. Residual block was antagonized without difficulty using neostigmine 2.5 mg. We discuss the relationship between plasma cholinesterase, acetylcholinesterase and anticholinesterase drugs.
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PMID:Mivacurium chloride and myasthenia gravis. 815 54

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

1. Due to their involvement in the termination of neurotransmission at cholinergic synapses and neuromuscular junctions, cholinesterases are the target proteins for numerous drugs of neuro-psychopharmacology importance. 2. In order to perform structure-function relationship studies on human cholinesterases with respect to such drugs, a set of expression vectors was engineered, all of which include cloned cDNA inserts encoding various forms of human acetyl- and butyrylcholinesterase. These vectors were designed to be transcribed in vitro into their corresponding mRNA products which, when microinjected into Xenopus oocytes, are efficiently translated to yield their catalytically active enzymes, each with its distinct substrate specificity and sensitivity to selective inhibitors. 3. A fully automated microtiter plate assay for evaluating the inhibition of said enzymes by tested cholinergic drugs and/or poisons has been developed, in conjunction with computerized data analysis, which offers prediction of such inhibition data on the authentic human enzymes and their natural or mutagenized variants. 4. Thus, it was found that asp70-->gly substitution renders butyrylcholinesterase succinylcholine insensitive and resistant to oxime reactivation while ser 425-->Pro with gly70 gives rise to the "atypical" butyrylcholinesterase phenotype, abolishing dibucaine binding. 5. Furthermore, differences in cholinesterase affinities to physostigmine, ecothiophate and bambuterol were shown in these natural variants. 6. Definition of key residues important for drug interactions may initiate rational design of more specific cholinesterase inhibitors, with fewer side effects. This, in turn, offers therapeutic potential in the treatment of clinical syndromes such as Alzheimer's and Parkinson's disease, glaucoma and myasthenia gravis.
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PMID:Structure-function relationship studies in human cholinesterases reveal genomic origins for individual variations in cholinergic drug responses. 827 1

We studied the effects of the intermittent methylprednisolone pulse (IMP) therapy without the maintenance steroid therapy for 6 children with myasthenia gravis; 3 cases with generalized type and 3 with ocular type. None of them was controlled satisfactorily by oral steroid therapy or anti-choline esterase agents. Two cases with generalized type and the other two with ocular type achieved remission by the initial pulse therapy, and were kept under good control by subsequent IMP therapy performed periodically or at the time of relapse. The other two cases could not be introduced to complete remission by the initial pulse therapy, but improved gradually by subsequent periodical IMP therapy. The IMP therapy without maintenance of oral steroid therapy is more useful as compared with oral administration of steroids, in controlling myasthenia gravis and also in preventing side effects due to steroid therapy.
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PMID:[Intermittent methylprednisolone pulse therapy for myasthenia gravis in childhood]. 828 Apr 41

A 42-year-old housewife with myasthenia gravis (MG) for 22 years, who was initially treated by radiation to the hyperplastic thymus and anti-cholinesterase therapy, developed bilateral ptosis, paresthesia of her right face and decreased taste sensation after house work at the age of 42 years. Neurological examinations revealed lateral and vertical gaze palsy, upward nystagmus, decreased taste sensation, peripheral facial palsy on the left side. She also had hypalgesia on the right face, arm and chest up to Th7 level, and urinary retention. She had hyperreflexia on the right side but no extensor toe signs. CSF study revealed 5 cells/microliters and protein of 23 mg/dl. Serum IgG anticardiolipin antibody was positive. Magnetic resonance imaging studies revealed high intensity areas in the brainstem tegmentum and periventricular white matter. Diagnosis of multiple sclerosis (MS) was made. This is the first case in which MG, MS and serum anticardiolipin antibody were present simultaneously, which may be all due to some immunological abnormality. Steroid therapy made anti-cardiolipin antibody negative, but new MS plaque developed in 7 months, which favors diagnosis of MS rather than infarction, since the activities of ACLA were not correlating to clinical symptoms. MRI was helpful in detecting MS plaques in MG patients.
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PMID:[A case of myasthenia gravis associated with multiple sclerosis and positive anticardiolipin antibodies]. 836 70

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


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