No abstract

Serotonin (5-HT) plays a crucial role in modulating the afferent fiber discharge rate in the inferior colliculus, auditory cortex, and other nuclei of the ascending auditory system. Resveratrol, a natural polyphenol phytoalexin, can inhibit serotonin transporters (SERT) to increase synaptic 5-HT levels. In this study, we investigated the effects of resveratrol on noise-induced damage in the serotonergic system. Male Sprague-Dawley rats were anaesthetized and exposed to an 8-kHz tone at 116 dB for 3.5 h. Resveratrol (30 mg/kg, intraperitoneal injection [IP]) and citalopram (20 mg/kg, IP), a specific SERT inhibitor used as a positive control, were administered once a day for four consecutive days, with the first treatment occurring 2 days before noise exposure. Auditory brainstem response testing and positron emission tomography (PET) with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM, a specific radioligand for SERT) were used to evaluate functionality of the auditory system and integrity of the serotonergic system, respectively, before and after noise exposure. Finally, immunohistochemistry was performed 1 day after the last PET scan. Our results indicate that noise-induced serotonergic fiber loss occurred in multiple brain regions including the midbrain, thalamus, hypothalamus, striatum, auditory cortex, and frontal cortex. This noise-induced damage to the serotonergic system was ameliorated in response to treatment with resveratrol and citalopram. However, noise exposure increased the hearing threshold in the rats regardless of drug treatment status. We conclude that resveratrol has protective effects against noise-induced loss of SERT.

The application of stereotactic ablative radiotherapy (SABR) to hepatocellular carcinoma (HCC) is emerging. To identify pretreatment prognostic indicators is crucial for patient selection and optimal individual therapy. The aim of this study was to determine whether 18 F-FDG PET and a combined 18 F-FDG-contrast CT parameter could be useful tools to predict tumor control for patients with HCC treated by SABR. Methods: We retrospectively identified 31 patients (41 tumors) who underwent 18 F-FDG PET before SABR between November 2007 and September 2011. 18 F-FDG PET parameters were collected as prognostic indicators, including visual PET scale (1/2), maximal standardized uptake value (SUV) of the tumor (T SUVmax ), ratio of T SUVmax to maximal normal-liver SUV, ratio of T SUVmax to mean normal-liver SUV, and score combining tumor volume and T SUVmax (CT/ 18 F-FDG PET score). They underwent SABR with a median dose of 42 Gy (ranging from 30 to 50 Gy) in 4-5 fractions. 18 F-FDG PET parameters and clinical factors were tested as predictors of tumor control and patient survival. Results: The median follow-up time was 18 mo. Among the parameters examined, T SUVmax and CT/ 18 F-FDG PET score were significantly correlated with tumor control. T SUVmax with a cutoff value of 3.2 was the most significant prognostic indicator. The 4-y control rate was 86.2% in tumors with a T SUVmax of 3.2 or less but only 37.5% in those with a T SUVmax of more than 3.2 (adjusted hazard ratio, 9.40; 95% confidence interval, 1.18-74.76; P 5 0.034). CT/ 18 F-FDG PET score (#4 vs. .4) was also a significant predictor of tumor control after SABR. Tumors with a CT/ 18 F-FDG PET score of more than 4 had a 5.23-fold risk of tumor failure. After adjustment for factors of sex, American Joint Committee on Cancer stage, Cancer of the Liver Italian Program score, and Child-Pugh classification, tumors with a score of more than 4 had a 4.96-fold risk of failure after SABR, compared with tumors with a score of 4 or less. For overall survival, none was statistically significant. Conclusion: The use of 18 F FDG PET to predict tumor control is feasible. T SUVmax with a cutoff value of 3.2 is the best prognostic indicator. We suggest that 18 F-FDG PET may be a reference for prognostic prediction, patient selection, and radiation dose adjustment for HCC patients treated with SABR.