RESUMEN
Introduction. Previous work has shown a strong association between alterations in cochlear vasculature, aging, and the development of presbycusis. The important role of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in angiogenesis suggests a potential role for involvement in this process. The aim of this study was to characterize vascular structure and VEGF and its' receptors in young and old C57 Mice. Methods. Young (4 weeks, n = 14) and aged (32-36 weeks, n = 14) C57BL/6 mice were used. Hearing was evaluated using auditory brainstem response. Cochleas were characterized with qRT-PCR, immunohistochemistry, and gross histological quantification. Results. Old C57 mice demonstrated significantly decreased strial area, blood vessel number, luminal size, and luminal area normalized to strial area (vascularity). qRT-PCR showed a significant upregulation of Flt-1, a VEGF receptor, in older animals. No differences were found in VEGF-A or Flk-1. Immunohistochemistry did not show any differences in staining intensity or area with age or cochlear turn location. Conclusion. The marked deafness of aged C57 mice could be in part meditated by loss of vascular development and alterations in VEGF signaling.
RESUMEN
BACKGROUND/AIMS: Low hepatic n-6 and n-3 polyunsaturated fatty acid (PUFA) may contribute to steatosis and steatohepatitis and can be affected by diet and oxidative stress. METHODS: Seventy-three patients referred for elevated liver enzymes and suspected NAFLD were assessed. Nutritional assessment, hepatic FA composition and oxidative stress were compared between these groups: simple steatosis (SS, n=18), steatohepatitis (NASH, n=38) and minimal findings on liver biopsy (MF, n=17). RESULTS: Patients with NASH had higher: BMI, central obesity, body fat, insulin resistance, dyslipidemia and lower physical activity compared to the other groups. They also had relatively lower hepatic n-3 and n-6 PUFA, a decrease in the ratio of metabolites to essential FA precursors for both n-6 and n-3 FA (eicosapentaenoic+docosahexaenoic/linolenic and arachidonic/linoleic acid ratios) and higher liver lipid peroxides with lower antioxidant power, when compared to MF. Overall, there was no significant difference between SS and NASH in FA composition. Self-reported dietary intake and red blood cell FA composition were similar among the three groups. CONCLUSIONS: NASH patients have more metabolic abnormalities. This is associated with higher oxidative stress and lower n-3 and n-6 PUFA in the liver in the absence of any differences in dietary FA composition.