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Benzodiazepines (Bzd) are known to interact with GABAergic inhibitory neurotransmission. Previous research on their effect on human auditory efferent pathways--through evoked otoacoustic emissions suppression by contralateral acoustic stimulation (CAS)--indicated a decrease in medial olivocochlear (MOC) efferent system inhibitory activity, after oral intake of oxazepam--representative of the Bzd drug class. To date, this pharmacological effect was only assessed in the right ear. Since a leftward asymmetry of Bzd receptors localization in human auditory cortex has been described recently, we explored in this study the hypothesis of an asymmetrical action of Bzd on MOC efferent functioning. The results revealed a significant difference of Bzd effect probing the right ear versus the left ear, with CAS-induced suppression being less effective in the right than left ear after oxazepam intake. This finding raises the question of possible neurochemical left-right asymmetry in the descending auditory pathways. The potential localization of this asymmetry is discussed.

By using otoacoustic emission, we looked for change in outer hair cell (OHC) motile activity and medial olivocochlear (MOC) system inhibition due to benzodiazepine administration, a drug that is known to produce a pharmacological effect by interacting with GABAergic inhibitory neurotransmission. No effect was observed on OHC motile activity, in contrast benzodiazepines decreased MOC system effectiveness suggesting the existence of GABAergic fibers projecting onto the MOC system.

Summary. After liver transplantation (LT) for hepatitis C virus (HCV)-related cirrhosis, recurrence of HCV infection is universal. The efficacy of antiviral therapy in this indication is usually reduced because of its poor tolerability. We present herein the results of plasma measurement of ribavirin levels in transplanted patients when using increasing dosage of ribavirin, in comparison with a control cohort of nontransplanted patients. Seventeen control patients (nine women and eight men, median age 51.5 years) were compared with 12 liver transplant patients (2 women and 10 men, median age 55 years). In 76% of patients, HCV infection was genotype 1. All patients were treated by a combination of ribavirin and pegylated-interferon α-2b. A total of 54 blood samples were taken (1.8 per patient) for ribavirin level measurement. A virological response was obtained in 8/17 patients in the control group and in 6/12 LT patients. Ribavirin dose was lower in the LT group (8.79 vs 12.98 mg/kg/day), but plasma levels were the same in both groups (2.23 vs 2.43 mg/L for LT and non-LT groups, respectively). This was probably related to impaired renal function in the LT group (serum creatinine: 112.6 vs 73.6 μmol/L). No discontinuation of ribavirin therapy was observed and haemoglobin level was the same in both groups (109.5 g/L in LT patients vs 119.5 g/L in the control group). These results strongly support the interest in plasma measurement of ribavirin concentration during antiviral therapy in LT patients. Ribavirin dosage might be adapted without compromising its efficacy.

The aim of this study was to test for an influence of benzodiazepine (BZD) on various perceptual and/or cognitive auditory processes. Loudness, auditory selective attention, and the ability of subjects to form perceptual streams out of alternating tone sequences were tested. Nine subjects were tested before, 1, 3, 7, and 24 h after a single-dose oxazepam vs placebo administration in a crossover design. A sample of blood allows us to measure plasma oxazepam concentration. The results revealed a significant reduction in stream segregation expressed as d′ scores 1 h after oxazepam intake in the test subjects. No significant change occurred across time in the same subjects when they were administrated a placebo in another session. Furthermore, oxazepam had no substantial and systematic influence either on auditory selective attention or on loudness perception. Altogether, these results suggest that the perceptual organization of sound sequences involves inhibitory neural mechanisms, which can be affected by BZDs. This outcome is consistent with existing models of auditory stream segregation and may be paralleled with earlier findings on the effect of BZDs on perceptual binding in the visual modality.

We have measured substance P-like (SPLI) and somatostatin-like (SLI) immunoreactivities in cerebrospinal fluid of 49 patients with peripheral (polyneuropathy, lumboischialgia) and spinal cord disease and in 16 control patients. The patient groups showed significantly higher CSF SPLI levels than controls while the mean SLI levels were unchanged. Fractionated sampling of CSF (total volume 30 ml) in 20 patients with various neurological diseases showed no significant differences between early and late fractions for SLI. In contrast, lumbar-cisternal concentration gradients were negative for SPLI, total protein and IgG, and positive for the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindolacetic acid. This suggests that SPLI may be released into the lumbar CSF from lower levels of the neuraxis, presumably the spinal cord and spinal ganglia, whereas SLI stems from diffuse CSF secretion without spinal preponderance.