salicylates and Nervous-System-Diseases

The drug 3,4-methylenedioxymethamphetamine (MDMA) is a serotonergic neurotoxicant that causes hyperthermia and depletion of serotonin (5-HT) and 5-hydroxy-indole-3-acetic acid (5-HIAA) in the central nervous system. Formation of neurotoxic metabolites of MDMA, e.g., 2,4,5-trihydroxy-methamphetamine and 2,4,5-trihydroxyamphetamine, involves hydroxyl and/or superoxide free radicals. The present study was designed to determine whether the hydroxyl free-radical-trapping agent salicylate could provide protection against MDMA neurotoxicity in rats. In the acute studies, sodium salicylate (12.5-400 mg/kg, calculated as free acid) was injected interperitoneally (i.p.) 1 h before subcutaneous (s.c.) injections of MDMA (20 mg/kg as base). In the chronic studies, sodium salicylate (3.1-100 mg/kg) was injected i.p. 1 h before repeated s.c. injections of MDMA (10 mg/kg as base, twice daily, at 0830 and 1730 h for 4 consecutive days). Repeated MDMA administration depleted contents of 5-HT and 5-HIAA in the frontal cortex, hippocampus and striatum. Coadministration of salicylate plus MDMA did not significantly alter MDMA-induced depletion of 5-HT and 5-HIAA in these tissues. Thus, salicylate, a hydroxyl free-radical-trapping agent, does not protect against MDMA-induced hyperthermia and depletion of 5-HT and 5-HIAA. These observations suggest that MDMA-induced neurotoxicity may occur mainly through the production of superoxide or other radicals rather than hydroxyl free radicals. Salicylate actually potentiated MDMA-induced hyperthermia and lethality, findings that might be of clinical relevance.

Topics: Adrenergic Uptake Inhibitors; Animals; Biogenic Monoamines; Body Temperature; Brain Chemistry; Free Radical Scavengers; Hydroxyl Radical; Injections, Intraperitoneal; Male; N-Methyl-3,4-methylenedioxyamphetamine; Nervous System Diseases; Rats; Rats, Sprague-Dawley; Salicylates; Salicylic Acid; Superoxides

Topics: Aged; Bismuth; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Nervous System Diseases; Organometallic Compounds; Salicylates; Substance-Related Disorders

A boy, 2 years old, developed a HUS after a pneumonitis. He was treated with Heparin, salicylates and recurrent peritoneal dialysis and recovered slowly. The course of the disease was complicated by myocarditis, gastric hemorrhage and severe neurologic disturbances. 7 days after unset of hemolysis a cold agglutinin titer of 1:256 was detected. This fact arises the question whether infection with Mycoplasma pneumoniae and the presence of cold agglutinins in serum could be involved in the development of HUS. The possibility of a viral etiology for this disease is discussed.

Topics: Agglutinins; Child, Preschool; Cold Temperature; Gastrointestinal Hemorrhage; Hemolysis; Hemolytic-Uremic Syndrome; Heparin; Humans; Lung Diseases; Male; Mycoplasma Infections; Myocarditis; Nervous System Diseases; Peritoneal Dialysis; Salicylates

Topics: Diet; Drug Hypersensitivity; Flavoring Agents; Food Additives; Food Hypersensitivity; Food Labeling; Gastrointestinal Diseases; Humans; Joint Diseases; Nervous System Diseases; Respiratory Hypersensitivity; Salicylates; Skin Diseases

Topics: Nervous System Diseases; Salicylamides; Salicylates