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)

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

Both organophosphorus (OP) and carbamate insecticides inhibit acetylcholinesterase (AChE), which results in accumulation of acetylcholine (ACh) at autonomic and some central synapses and at autonomic postganglionic and neuromuscular junctions. As a consequence, ACh binds to, and stimulates, muscarinic and nicotinic receptors, thereby producing characteristic features. With OP insecticides (but not carbamates), "aging" may also occur by partial dealkylation of the serine group at the active site of AChE; recovery of AChE activity requires synthesis of new enzyme in the liver. Relapse after apparent resolution of cholinergic symptoms has been reported with OP insecticides and is termed the intermediate syndrome. This involves the onset of muscle paralysis affecting particularly upper-limb muscles, neck flexors, and cranial nerves some 24-96 hours after OP exposure and is often associated with the development of respiratory failure. OP-induced delayed neuropathy results from phosphorylation and subsequent aging of at least 70% of neuropathy target esterase. Cramping muscle pain in the lower limbs, distal numbness, and paresthesiae are followed by progressive weakness, depression of deep tendon reflexes in the lower limbs and, in severe cases, in the upper limbs. The therapeutic combination of oxime, atropine, and diazepam is well established experimentally in the treatment of OP pesticide poisoning. However, there has been controversy as to whether oximes improve morbidity and mortality in human poisoning. The explanation may be that the solvents in many formulations are primarily responsible for the high morbidity and mortality; oximes would not be expected to reduce toxicity in these circumstances. even if given in appropriate dose.
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PMID:Organophosphorus and carbamate insecticide poisoning. 2656 88