Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The data reviewed in this paper indicate that spontaneous fibrillations do not involve a cholinergic mechanism since non-depolarizing anticholinesterase drugs such as Mestinon fail to increase spontaneous fibrillations in denervated muscle. Fibrillation potentials are related to the changes in electrical properties of the membrane of denervated muscle fibres which lead to the appearance of spontaneous subthreshold depolarizations, sometimes triggering a propagated potential. Fibrillations seem to appear in cycles and this may depend on the depression of spontaneous depolarization by muscle activity itself. Fibrillations are also an important feature of Duchenne muscular dystrophy and polymyositis, but they have not been found in Landouzy-Dejerine muscular dystrophy. These "myopathic" fibrillations probably arise from subthreshold depolarizations in the membrane of muscle fibre segments which have been functionally or anatomically isolated from the end-plate by a pathological lesion (Fig. 4). Experimental demonstration of spontaneous fibrillations in baboon biceps muscles after extrajunctional myotomies indicates that such an isolated muscle fibre segment can indeed develop and sustain spontaneous fibrillation activities. Studies of motor unit potentials in myopathies by "coherent" electromyography disclose linked potentials after the main potential in Duchenne dystrophy, but not in Landouzy-Dejerine muscular dystrophy. The linked potentials are signs of collateral innervation by sprouts of the motor axons. The fact that linked potentials occur in Duchenne dystrophy, including in obviously dystrophic motor units (Fig. 5), shows that such motor axons are quite healthy and able to sprout efficiently. The muscle fibres thus innervated collaterally are probably the ones which fibrillated and were deprived of trophic motor control as a result of myopathic lesions of the type considered in Fig.4. This correlation receives support from the finding that both spontaneous fibrillations and linked potentials are lacking in Landouzy-Dejerine muscular dystrophy, which obviously presents a different type of muscle lesion.
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PMID:Muscular dystrophy contrasted with denervation: different mechanisms underlying spontaneous fibrillations. 10 83

The neuromuscular junctions from diaphragm, soleus, and extensor digitorum longus (EDL) muscles of male albino rats were assessed for morphological alterations following acute (30-min) and subacute (2-day) exposure to pyridostigmine bromide in Mestinon-equivalent buffer. These muscles were selected to compare the effects of the drug on muscles of different fiber type composition. The diaphragm has approximately equal numbers of type I and type II fibers while the soleus and EDL possess primarily type I and type II fibers, respectively. Pyridostigmine was administered to each acute-exposure animal by a single subcutaneous injection of 0.36 mg/kg pyridostigmine and to each subacute-exposure animal by a subcutaneously implanted osmotic minipump containing 10 mg/ml pyridostigmine. Both treatments resulted in whole blood cholinesterase (ChE) depression of approximately 60-70% as determined by radiometric assay. Control animals received only Mestinon-equivalent buffer. Both acute and subacute exposures resulted in morphological alteration of the neuromuscular junctions (NMJs) of all three muscles, although considerable variation in the extent of damage occurred even within individual NMJs. The most frequently observed presynaptic alterations were mitochondrial damage and partial withdrawal of nerve terminal branches (partial denervation). Post-synaptic changes included occasional rarefaction of mitochondrial matrices and disruption of the myofibrillar organization in small numbers of subjunctional sarcomeres. The data indicate that acute or subacute exposure to pyridostigmine bromide at a whole blood ChE depression of 60-70% results in similar alterations to the NMJs of three muscles with substantially different fiber type compositions. Although the severity of the damage varies from fiber to fiber, the variability appears random and not related to a specific fiber type or dosage regimen.
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PMID:Neuromuscular toxicity of pyridostigmine bromide in the diaphragm, extensor digitorum longus, and soleus muscles of the rat. 409 93