Effect of Fenofibrate on the Expression of Inflammatory Mediators in a Diabetic Rat Model.

Purpose: To investigate the mechanisms of anti-inflammatory and anti-oxidative effects of fenofibrate, a peroxisome proliferator-activated receptors-α agonist, in preventing diabetic retinopathy (DR) progression via a diabetic rat model. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin in 6-week-old female Wistar rats. Diabetic rats were divided into diabetes without treatment (n = 10), diabetes treated with low dose fenofibrate (30 mg/kg/day) (n = 10) and high dose fenofibrate (100 mg/kg/day) (n = 10). Serum aqueous humor (AqH) and ocular tissues were gathered after 3-month treatment. Expressions of NF-κB and inflammatory chemokines (monocyte chemoattractant protein-1, fractalkine, and intercellular adhesion molecule-1) were detected by reverse transcription-polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and electrophoretic mobility shift assay. The levels of oxidative biomarkers, including acrolein, nitrotyrosine, and 8-hydroxy-2'-deoxyguanosin (8-OHdG), were determined by IHC and ELISA. The reactive oxygen species (ROS) levels in serum and AqH were measured by chemiluminescence methods. Results: After 3 months of treatment, the expressions of mRNA and protein of monocyte chemoattractant protein-1, fractalkine, and intercellular adhesion molecule-1 in the retina of diabetic rats were significantly inhibited by fenofibrate in a dose-dependent manner. These effects were mediated by inhibition of NF-κB by fenofibrate. The levels of oxidative markers, including acrolein, nitrotyrosine, and 8-OHdG, decreased in the retina of diabetic rats after fenofibrate treatment. The ROS levels in the AqH of diabetic rats also suppressed by fenofibrate. Conclusions: Fenofibrate significantly inhibited the expressions of NF-κB and inflammatory chemokines and reduced oxidative products within diabetic retina. Treatment of fenofibrate might be beneficial to preventing DR progression.

Waist circumference is associated with pitch pattern sequence score in older male adults.

OBJECTIVE: While obesity may increase the risk for neurodegenerative diseases such as Alzheimer's disease, the relationship between waist circumference (WC) and central auditory dysfunction is unknown. We aimed to investigate the relationship of WC and pitch pattern sequence (PPS) score in adults. DESIGN: The association of WC with PPS score was analysed. STUDY SAMPLE: Volunteer helpers at a community hospital, 391 adults ≥40 years, with normal or symmetrical sensorineural hearing loss were randomly selected. RESULTS: After adjusting for age, gender, pure-tone average, systemic diseases, and habits, WC was significantly negatively associated with PPS. In a subgroup analysis by gender and age, the PPS score was negatively associated with WC only for males who were older than 55 years old, but not for males who were younger than 55 years old or females in either age group. Meanwhile, central obesity showed positive association with abnormal PPS recognition ability (PPS score < 90%) of borderline significance only for males who were older than 55 years old, but not for males who were younger than 55 years old or females in both age groups. CONCLUSIONS: WC or central obesity is an independent risk factor for poor central auditory function, especially in older male subjects.