L- and D- methionine provide equivalent long term protection against CDDP-induced ototoxicity in vivo, with partial in vitro and in vivo retention of antineoplastic activity.

Treatment of metastatic tumors with ionic platinum compounds is hampered by the potent nephrotoxic, ototoxic and neurotoxic properties of these drugs. Recent studies have shown that sulfur-containing antioxidants relieve the dose limiting side effects of cis-diamminedichloroplatinum (CDDP), the most commonly used ionic platinum therapy. Here we report that both isomers of the sulfur-containing antioxidant methionine (MET) completely block the in vivo ototoxic and nephrotoxic effects of CDDP, and the duration of MET otoprotection is longer than has been previously reported. Rats treated with either L- or D-MET in addition to CDDP exhibited no signs of auditory system damage after 7 days, as evaluated by the auditory brainstem response and scanning electron microscopic examination of the organ of Corti, while CDDP-treated rats exhibited pronounced evidence of ototoxic damage after only 3 days. Microscopic examination of kidney tissue revealed moderate to severe nephrotoxic damage to CDDP-treated rats after 5 days, while rats co-treated with either MET isomer showed no evidence of kidney damage. Mortality among CDDP-treated subjects increased steadily over the period of the study, while all of the MET-protected rats survived. Finally, the efficacy of CDDP in the presence of L- or D-MET was evaluated in vitro using cultures of MTLN-3 breast tumor cell lines, and in vivo using implanted MTLN-3 tumors. Both L- and D-MET reduced the ability of CDDP to kill tumor cells in vitro and in vivo, however, our data suggest that a higher proportion of the antineoplastic activity of CDDP is retained in the presence of L- MET.

Normal time course of auditory recognition in schizophrenia, despite impaired precision of the auditory sensory ("echoic") memory code.

Prior studies have demonstrated impaired precision of processing within the auditory sensory memory (ASM) system in schizophrenia. This study used auditory backward masking to evaluate the degree to which such deficits resulted from impaired overall precision versus premature decay of information within the short-term auditory store. ASM performance was evaluated in 14 schizophrenic participants and 16 controls. Schizophrenic participants were severely impaired in their ability to match tones following delay. However, when no-mask performance was equated across participants, schizophrenic participants were no more susceptible to the effects of backward maskers than were controls. Thus, despite impaired precision of ASM performance, schizophrenic participants showed no deficits in the time course over which short-term representations could be used within the ASM system.