Nitric oxide differentially regulates renal ATP-binding cassette transporters during endotoxemia

Nitric oxide (NO) is an important regulator of renal transport processes. In the present study, we investigated the role of NO, produced by inducible NO synthase (iNOS), in the regulation of renal ATP-binding cassette (ABC) transporters in vivo during endotoxemia. Wistar–Hannover rats were injected with lipopolysaccharide (LPS+) alone or in combination with the iNOS inhibitor, aminoguanidine. Controls received detoxified LPS (LPS−). After LPS+, proximal tubular damage and a reduction in renal function were observed. Furthermore, iNOS mRNA and protein, and the amount of NO metabolites in plasma and urine, increased compared to the LPS− group. Coadministration with aminoguanidine resulted in an attenuation of iNOS induction and reduction of renal damage. Gene expression of 20 ABC transporters was determined. After LPS+, a clear up-regulation in Abca1, Abcb1/P-glycoprotein (P-gp), Abcb11/bile salt export pump (Bsep), and Abcc2/multidrug resistance protein (Mrp2) was found, whereas Abcc8 was down-regulated. Up-regulation of Abcc2/Mrp2 was accompanied by enhanced calcein excretion. Aminoguanidine attenuated the effects on transporter expression. Our data indicate that NO, produced locally by renal iNOS, regulates the expression of ABC transporters in vivo. Furthermore, we showed, for the first time, expression and subcellular localization of Abcb11/Bsep in rat kidney

Baker-IV capsular contracture is correlated with an increased amount of silicone material: an intra-patient study

BACKGROUND: Breast implant surgery is one of the most frequently performed procedures by plastic surgeons worldwide. However, the relationship between silicone leakage and the most common complication, capsular contracture, is far from understood. This study aimed to compare Baker-I with Baker-IV capsules regarding their silicone content in an intra-donor setting, using two previously validated imaging techniques. METHODS: Twenty-two donor-matched capsules from eleven patients experiencing unilateral complaints were included after bilateral explantation surgery. All capsules were examined using both Stimulated Raman Scattering (SRS) imaging and staining with Modified Oil Red O (MORO). Evaluation was done visually for qualitative and semi-quantitative assessment and automated for quantitative analysis. RESULTS: Using both SRS and MORO techniques, silicone was found in more Baker-IV capsules (8/11 and 11/11, respectively) than in Baker-I capsules (3/11 and 5/11, respectively). Baker-IV capsules also showed significantly more silicone content compared to the Baker-I capsules. This was true for semi-quantitative assessment for both SRS and MORO techniques (p=0.019 and p=0.006, respectively), while quantitative analysis proved to be significant for MORO alone (p=0.026 vs. p=0.248 for SRS). CONCLUSIONS: In this study, a significant correlation between capsule silicone content and capsular contracture is shown. An extensive and continued foreign body response to silicone particles is likely to be responsible. Considering the widespread use of silicone breast implants these results affect many women worldwide and warrant a more focused research effort

Entrepreneurship and Innovation Program Annual Report - Research 2011

The Entrepreneurship and Innovation Program at the University of Sydney Business School focuses on identifying, nurturing and strengthening entrepreneurial communities of learning and practice. This 2011 Annual Report sets out our research activities and achievements, as catalysts for community and action