Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We hypothesized that hindlimb suspension unloading of 8-day-old neonatal rats would disrupt the normal development of muscle fiber types and the motor innervation of the antigravity (weightbearing) soleus muscles but not extensor digitorum longus (EDL) muscles. Five rats were suspended 4.5 h and returned 1.5 h to the dam for nursing on a 24 h cycle for 9 days. To control for isolation from the dam, the remaining five littermates were removed on the same schedule but not suspended. Another litter of 10 rats housed in the same room provided a vivarium control. Fibers were typed by myofibrillar ATPase histochemistry and immunostaining for embryonic, slow, fast IIA and fast IIB isomyosins. The percentage of multiple innervation and the complexity of singly-innervated motor terminal endings were assessed in silver/cholinesterase stained sections. Unique to the soleus, unloading accelerated production of fast IIA myosin, delayed expression of slow myosin and retarded increases in standardized muscle weight and fiber size. Loss of multiple innervation was not delayed. However, fewer than normal motor nerve endings achieved complexity. Suspended rats continued unloaded hindlimb movements. These findings suggest that motor neurons resolve multiple innervation through nerve impulse activity, whereas the postsynaptic element (muscle fiber) controls endplate size, which regulates motor terminal arborization. Unexpectedly, in the EDL of unloaded rats, transition from embryonic to fast myosin expression was retarded. Suspension-related foot drop, which stretches and chronically loads EDL, may have prevented fast fiber differentiation. These results demonstrate that neuromuscular development of both weightbearing and non-weightbearing muscles in rats is dependent upon and modulated by hindlimb loading.
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PMID:Effects of hindlimb unloading on neuromuscular development of neonatal rats. 1067 66

Organophosphate-induced delayed polyneuropathy (OPIDP) is a rare toxicity resulting from exposure to certain organophosphorus (OP) esters. It is characterised by distal degeneration of some axons of both the peripheral and central nervous systems occurring 1-4 weeks after single or short-term exposures. Cramping muscle pain in the lower limbs, distal numbness and paraesthesiae occur, followed by progressive weakness, depression of deep tendon reflexes in the lower limbs and, in severe cases, in the upper limbs. Signs include high-stepping gait associated with bilateral foot drop and, in severe cases, quadriplegia with foot and wrist drop as well as pyramidal signs. In time, there might be significant recovery of the peripheral nerve function but, depending on the degree of pyramidal involvement, spastic ataxia may be a permanent outcome of severe OPIDP. Human and experimental data indicate that recovery is usually complete in the young. At onset, the electrophysiological changes include reduced amplitude of the compound muscle potential, increased distal latencies and normal or slightly reduced nerve conduction velocities. The progression of the disease, usually over a few days, may lead to non-excitability of the nerve with electromyographical signs of denervation. Nerve biopsies have been performed in a few cases and showed axonal degeneration with secondary demyelination. Neuropathy target esterase (NTE) is thought to be the target of OPIDP initiation. The ratio of inhibitory powers for acetylcholinesterase and NTE represents the crucial guideline for the aetiological attribution of OP-induced peripheral neuropathy. In fact, pre-marketing toxicity testing in animals selects OP insecticides with cholinergic toxicity potential much higher than that to result in OPIDP. Therefore, OPIDP may develop only after very large exposures to insecticides, causing severe cholinergic toxicity. However, this was not the case with certain triaryl phosphates that were not used as insecticides but as hydraulic fluids, lubricants and plasticisers and do not result in cholinergic toxicity. Several thousand cases of OPIDP as a result of exposure to tri-ortho-cresyl phosphate have been reported, whereas the number of cases of OPIDP as a result of OP insecticide poisoning is much lower. In this article, we mainly discuss OP pesticide poisoning, particularly when caused by chlorpyrifos, dichlorvos, isofenphos, methamidophos, mipafox, trichlorfon, trichlornat, phosphamidon/mevinphos and by certain carbamates. We also discuss case reports where neuropathies were not convincingly attributed to fenthion, malathion, omethoate/dimethoate, parathion and merphos. Finally, several observational studies on long-term, low-level exposures to OPs that sometimes reported mild, inconsistent and unexplained changes of unclear significance in peripheral nerves are briefly discussed.
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PMID:Organophosphate-induced delayed polyneuropathy. 1604 3