Acetophenone protection against cisplatin-induced end-organ damage.

Cisplatin is a widely used and efficacious chemotherapeutic agent for treating solid tumors, yet it causes systemic end-organ damage that is often irreversible and detrimental to quality of life. This includes severe sensorineural hearing loss, hepatotoxicity, and renal injury. Based on the hard-soft acid-base theory, we recently developed two acetophenone-derived, enol-based compounds that directly interfere with the side effects of cisplatin. We investigated organ-specific and generalized toxicity in order to define dose-dependent responses in rodents injected with cisplatin with or without the protective compounds. All metrics that were used as indicators of toxicity showed retention of baseline or control measurements when animals were pre-treated with acetophenones prior to cisplatin administration, while animals injected with no protective compounds showed expected elevations in toxicity measurements or depressions in measurements of organ function. These data support the further investigation of novel acetophenone compounds for the prevention of cisplatin-induced end-organ toxicity.

Intracortical responses in human and monkey primary auditory cortex support a temporal processing mechanism for encoding of the voice onset time phonetic parameter.

This study tests the hypothesis that temporal response patterns in primary auditory cortex are potentially relevant for voice onset time (VOT) encoding in two related experiments. The first experiment investigates whether temporal responses reflecting VOT are modulated in a way that can account for boundary shifts that occur with changes in first formant (F1) frequency, and by extension, consonant place of articulation. Evoked potentials recorded from Heschl's gyrus in a patient undergoing epilepsy surgery evaluation are examined. Representation of VOT varies in a manner that reflects the spectral composition of the syllables and the underlying tonotopic organization. Activity patterns averaged across extended regions of Heschl's gyrus parallel changes in the subject's perceptual boundaries. The second experiment investigates whether the physiological boundary for detecting the sequence of two acoustic elements parallels the psychoacoustic result of approximately 20 ms. Population responses evoked by two-tone complexes with variable tone onset times (TOTs) in primary auditory cortex of the monkey are examined. Onset responses evoked by both the first and second tones are detected at a TOT separation as short as 20 ms. Overall, parallels between perceptual and physiological results support the relevance of a population-based temporal processing mechanism for VOT encoding.