The Impact of Pesticides - Academy Publish

1982; Lotti, 1992; Jokanović et al., 2004). By the end of twentieth century, therewere many cases of OPIDP due to TOCP poisoning in Romania, Sri Lanka, formerYugoslavia and China. In addition to TOCP, several other OP pesticides have beenreported to cause OPIDP in man (Table 2) (Jokanović et al., 2002; Lotti andMoretto, 2005; Jokanović and Kosanović 2010). Cases of OPIDP caused bypesticides were discussed in more details by Lotti and Moretto (2005).OPIDP is relatively rare neurodegenerative disorder in humans that is characterizedby loss of function and ataxia of distal parts of sensory and motor axons inperipheral nerves and ascending and descending tracts of spinal cord. The earlyneurological symptoms usually are sharp, cramp-like pains in the calves, tingling inthe feet and hands followed by distal numbness and paresthesia. Pain and weaknessin muscles spread rapidly and patients become unsteady and unable to keep theirbalance. Progressive leg weakness occurs, together with depression of tendonreflexes. Symptoms may also appear in the arms and forearms. Sensory loss may bemild. Muscle tonus of the limbs gradually increase and spasticity appears in thelower limbs. Physical examination reveals distal symmetrical mainly motorpolyneuropathy, with wasting and flaccid weakness of distal limb muscles,especially in the lower limbs. In severe OPIDP quadriplegia with foot and wristdrop were observed as well as mild pyramidal signs (Lotti, 1992). There may besome functional recovery in less severe cases with more distal involvement andsparing of spinal cord axons, but pyramidal and other signs of central neurologicalinvolvement may become more evident with time. The recovery affects onlysensory nerves, while motor neurons may permanently lose its function as indicatedby Morgan (1982) who described the lack of improvement during 47 years in 11patients poisoned with TOCP. The prognosis for functional recovery depends on thedegree of pyramidal involvement with ataxia and paralysis representing a permanentoutcome of severe OPIDP. It appears that clinical signs of OPIDP in children areconsiderably milder than in adults (Jokanović et al., 2004; Lotti and Moretto, 2005;Jokanović, 2009b).OPIDP is initiated by phosphorylation and subsequent aging of >70% neuropathytarget esterase (NTE) in peripheral nerves. Carbamates, sulfonates and phosphinatesalso covalently bind to NTE but cannot undergo aging reaction, and as a result,these inhibitors do not cause OPIDP. When given to experimental animals before aneuropathic OP they protect from OPIDP by occupying NTE active site (Johnson,1982; Lotti, 1992).NTE was discovered by Martin Johnson, who described the most importanttoxicological and biochemical features of this esterase (Johnson, 1982). NTE is anintegral membrane protein in vertebrate neurons present in all neurons, but not in glia.The active site of NTE contains Ser 966 and two aspartates Asp 960 and Asp 1086 that appearessential for enzymatic activity. It was shown that human NTE catalyses hydrolysis ofmembrane-associated lipids with possible involvement in intracellular membranetrafficking. NTE may have important functions during brain development throughinvolvement in a cell-signaling pathway between neurons and glial cells (Glynn, 1999;van Tienhoven et al., 2002; Glynn, 2006). Physiological role and importance of NTEwere recently discussed by Jokanović et al. (2011).Medical treatment of OPIDP in humans is symptomatic. Standard treatment of OPpoisoned patients comprising atropine, oxime and diazepam was not effective intreatment of OPIDP. However, there were several reports in the literature describingattempts of treatment of OPIDP in animals and these studies were reviewed by Lotti(1992) and Jokanović et al. (2004; 2011), but none of these treatments have been testedin patients so far.AcademyPublish.org - The Impact of Pesticides44