pralidoxime and Peripheral-Nervous-System-Diseases

The present study was designed to investigate the ameliorative effects of clinically available drugs, with Na+/Ca2+ and Na+/H+ exchange inhibitory actions, in chronic constriction injury and vincristine induced painful neuropathy in rats. Sciatic nerve ligation and vincristine treatment (50 microg/kg for 10 days) was employed to induce neuropathy in rats. Paw pressure, von Frey hair, acetone drop, and tail heat immersion tests were performed to assess degree of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal thermal sensation respectively. Axonal degeneration of sciatic nerve was assessed histopathologically. The levels of thio-barbituric acid reactive species, reduced glutathione, and total calcium were determined to assess biochemical alterations. Amiloride (15 mg/kg i.p.), Na+/Ca2+ and Na+/H+ exchange inhibitor, and pralidoxime (20 mg/kg i.p.), Na+/Ca2+ exchange inhibitor, were administered for 10 consecutive days starting from the day of surgery or vincristine administration. Sciatic nerve ligation and vincristine treatment resulted in significant axonal degeneration, development of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal heat hyperalgesia and also resulted in rise in thio-barbituric acid reactive species, total calcium and decrease in reduced glutathione levels. Administration of amiloride and pralidoxime attenuated chronic constriction injury and vincristine induced axonal degeneration and reduction of nociceptive threshold along with reduction in calcium levels and oxidative stress. The observed anti-nociceptive effects of amiloride and pralidoxime may possibly be attributed to inhibition of Na+/Ca2+ and Na+/H+ exchangers with subsequent decrease in Ca2+ ions and oxidative stress.

Topics: Amiloride; Animals; Antineoplastic Agents, Phytogenic; Axons; Calcium; Cholinesterase Reactivators; Cold Temperature; Constriction, Pathologic; Diuretics; Female; Hot Temperature; Male; Oxidative Stress; Pain Measurement; Peripheral Nervous System Diseases; Physical Stimulation; Pralidoxime Compounds; Pressure; Rats; Rats, Wistar; Sciatic Neuropathy; Sodium-Calcium Exchanger; Sodium-Hydrogen Exchangers; Thiobarbituric Acid Reactive Substances; Vincristine

Poisoning with organophosphate pesticides can cause sensory and motor neuropathy with permanent paralysis. Paralysis at the site of dermal exposure has not been reported.. A 61-year-old carpenter sprayed a nest of termites with an insecticide containing chlorpyrifos without protective equipment and with direct contact of pesticide solution to hands, lower arms, feet, and lower legs, as well as inhalation of vapors from spraying. After 30 min he became ill with nausea, abdominal cramping, arm and leg weakness, bilateral shoulder pain, chest pain, and numbness in the left hand and arm. At a hospital, he was treated with atropine 1 mg IV and pralidoxime Cl 2 g IV There was 0/5 strength in the hands and wrists and 3/5 elsewhere, a left peritoneal palsy, and urinary retention. He was transferred to a tertiary care hospital where paralysis persisted. Electromyogram studies documented widespread peripheral neuropathy. With continued progression of neuropathy, pralidoxime was repeated on the third day. By day 12, motor strength improved except for the hands and left lower leg. Right interosseous muscle strength was 1/5 and left was 0/5. Right-hand grip was 2/5, and left-hand grip was 0/5. He was transferred to a rehabilitation center. He never regained use of his hands and was disabled from employment as a carpenter. There was a disturbed gait, with inability to clear his left foot with walking. Urinary retention persisted and required self-catherization.. Dermal exposure of the hands and feet to chlorpyrifos was associated with atrophy and permanent paralysis of exposed areas. The importance of protective equipment is emphasized.

Topics: Atropine; Chlorpyrifos; Cholinesterase Reactivators; Humans; Insecticides; Male; Middle Aged; Muscarinic Antagonists; Muscle Weakness; Paralysis; Peripheral Nervous System Diseases; Pralidoxime Compounds

An acute poisoning in a 44-y-old female who ingested 50 ml of ethyl parathion concentrate (25 g) is described. She was treated by gastric lavage, administration of pralidoxime and atropine, and mechanical ventilation. As signs of intoxication disappeared at day 3, treatment was discontinued. The patient had a relapse of acute cholinergic crisis at day 4, and the same treatment was applied again. The acute poisoning phase was followed by an intermediate syndrome and delayed distal polyneuropathy. The clinical course of this severe ethyl parathion poisoning was favorable after 40 d.

Topics: Acute Disease; Adult; Atropine; Cholinesterase Reactivators; Drug Overdose; Drug Therapy, Combination; Female; Gastric Lavage; Humans; Insecticides; Muscles; Parathion; Peripheral Nervous System Diseases; Pralidoxime Compounds; Recurrence; Respiration, Artificial; Suicide, Attempted; Syndrome; Treatment Outcome