In addition, Brissoni et al. have recently shown that Tollip is required in the sorting of the IL-1RI at late endosomes, further clarifying its involvement in the IL-1 inflammatory pathway. Zhang and Ghosh have shown that Tollip associates not only with IL-1RI but also with the TLR2 and TLR4 receptors when activated by LPS stimulation. Also this interaction results in the suppression of TLR-mediated cellular responses through the inhibition of phosphorylation and kinase activity of IRAK1. Hence, disruption of the prion structure or its interaction with these endogenous factors would impede PrPc conversion, cellular distribution and neuropathology. Although many potential biomarkers , inhibin B , BMP-15 ) in follicular fluid have been suggested to discriminate between mature and immature oocytes, none of these are in current clinical practice. In this regard, the ROC analysis demonstrating that a 1.09 nM follicular fluid AEA level was predictive of mature oocytes in 77.14% of the cases is especially encouraging. Although this study clearly indicates that follicular fluid AEA levels are associated with both follicle and oocyte maturity, there are likely to be a number of other factors that influence oocyte maturity and quality in the local hormonal environment that we do not know about. It would be ideal to relate the follicular fluid and plasma AEA levels with oocyte/embryo quality in women with different causes of infertility; however, the numbers in this study were too small for such sub-analyses. We believe that follicular fluid AEA levels should be further investigated as a possible biomarker for the assessment of oocyte maturity in advanced reproductive technology procedures. This needs to be done in conjunction with other biomarkers. With regards to the embryo quality we did not find a significant association between follicular fluid AEA concentrations and embryo quality. This suggests that several other factors including sperm quality are involved in determining embryo quality. The fact that there was no significant difference between plasma and follicular fluid AEA concentrations at the time of oocyte collection suggests that systemic AEA concentrations reflect ovarian AEA levels. Also, plasma AEA concentrations in women undergoing IVF/ICSI at the time of oocyte collection were similar to those found in women at ovulation in natural cycles which suggest that plasma AEA is involved in the ovulation process whether it occurred naturally or was stimulated. The disparity observed in the bioactivity of anti-prion agents such as polyene antibiotics and Adriamycin structure tricyclic compounds among prion strains may reflect their differing ability to disrupt PrPsc interaction with strain specific proteins. These agents likely interrupt innate PrPsc+ protein interaction thereby modifying PrPsc distribution and associated cellular conversion events. These changes might reduce the rate or site of PrPsc accumulation thereby decreasing efficacy of prion transmission.