Ardavan Akhavan

Cell surface biliverdin reductase mediates biliverdin-induced anti-inflammatory effects via phosphatidylinositol 3-kinase and Akt.

Biliverdin reductase A (BVR) catalyzes the reduction of biliverdin (BV) to bilirubin (BR) in all cells. Others and we have shown that biliverdin is a potent anti-inflammatory molecule, however, the mechanism by which BV exerts its protective effects is unclear. We describe and elucidate a novel finding demonstrating that BVR is expressed on the external plasma membrane of macrophages (and other cells) where it quickly converts BV to BR. The enzymatic conversion of BV to BR on the surface by BVR initiates a signaling cascade through tyrosine phosphorylation of BVR on the cytoplasmic tail. Phosphorylated BVR in turn binds to the p85α subunit of phosphatidylinositol 3-kinase and activates downstream signaling to Akt. Using bacterial endotoxin (lipopolysaccharide) to initiate an inflammatory response in macrophages, we find a rapid increase in BVR surface expression. One of the mechanisms by which BV mediates its protective effects in response to lipopolysaccharide is through enhanced production of interleukin-10 (IL-10) the prototypical anti-inflammatory cytokine. IL-10 regulation is dependent in part on the activation of Akt. The effects of BV on IL-10 expression are lost with blockade of Akt. Inhibition of surface BVR with RNA interference attenuates BV-induced Akt signaling and IL-10 expression and in vivo negates the cytoprotective effects of BV in models of shock and acute hepatitis. Collectively, our findings elucidate a potentially important new molecular mechanism by which BV, through the enzymatic activity and phosphorylation of surface BVR (BVR)surf modulates the inflammatory response.

The proportion of cores with high‐grade prostatic intraepithelial neoplasia on extended‐pattern needle biopsy is significantly associated with prostate cancer on site‐directed repeat biopsy

To determine whether the predictive value of isolated high‐grade prostatic intraepithelial neoplasia (HGPIN) for an unsampled prostate cancer on an extended biopsy is lower due to more thorough prostate sampling, and whether the proportion of cores with HGPIN is associated with prostate cancer, as isolated HGPIN on sextant prostate biopsy is associated with a 27–57% risk of prostate cancer on repeat biopsy.

Translocator Protein Blockade Reduces Prostate Tumor Growth

Purpose: The transmembrane molecule, translocator protein (TSPO), has been implicated in the progression of epithelial tumors. TSPO gene expression is high in tissues involved in steroid biosynthesis, neurodegenerative disease, and in cancer, and overexpression has been shown to contribute to pathologic conditions including cancer progression in several different models. The goal of our study was to examine the expression and biological relevance of TSPO in prostate cancer and show that the commonly prescribed benzodiazepine lorazepam, a ligand for TSPO, exhibits anticancer properties. Experimental Design: Immunohistochemical analysis using tissue microarrays was used to determine the expression profile of TSPO in human prostate cancer tissues. To show the effect of TSPO ligands (lorazepam and PK11195) in prostate cancer, we used cell proliferation assays, apoptosis ELISA, prostate cancer xenograft study, and immunohistochemistry. Results: TSPO expression is increased in prostatic intraepithelial neoplasia, primary prostate cancer, and metastases compared with normal prostate tissue and benign prostatic hyperplasia. Furthermore, TSPO expression correlates with disease progression, as TSPO levels increased with increasing Gleason sum and stage with prostate cancer metastases demonstrating the highest level of expression among all tissues examined. Functionally, we have shown that lorazepam has antiproliferative and proapoptotic properties in vitro and in vivo. Additionally, we have shown that TSPO overexpression in nontumorigenic cells conferred susceptibility to lorazepam-induced growth inhibition. Conclusion: These data suggest that blocking TSPO function in tumor cells induces cell death and denotes a survival role for TSPO in prostate cancer and provides the first evidence for the use of benzodiazepines in prostate cancer therapeutics. (Clin Cancer Res 2009;15(19):6177–84)

Simple, Age-based Formula for Predicting Renal Length in Children

OBJECTIVE To determine a simple, age based formula for predicting ideal renal length in children. Renal size is a valuable marker in the evaluation of children with urological disorders. Although many authors have described complex nomograms and multivariate formulas for determining renal size, we propose a simple and accurate formula. MATERIAL AND METHODS All renal ultrasound (US) studies performed over a 9-year period in patients <18 years of age were retrospectively evaluated, excluding patients with a history of urinary tract disease or with abnormal renal US findings. RESULTS Ultrasounds were performed in 778 children <18 years who met inclusion criteria. Sixty-one percent of the patient population was ≥1 year of age at the time of the US. Forty-four percent of the children were male. In children 1 year of age or older, the formula was length (cm) = age (years) × 0.3 + 6, R(2) = .81. In infants younger than 1 year, renal length was poorly estimated by a simple age-based formula. CONCLUSION Our proposed formula can be used to predict renal length in children older than 1 year.

Complications and Management of Pediatric Robotic-Assisted Laparoscopic Surgery: Prevention and Management

As the application and popularity of pediatric robotic urology increases, the practicing urologist must become familiar with possible complications. While there is a dearth of literature on pediatric robotic outcomes in urological surgery, there is an even greater paucity of publications on robotic complications in children. In theory, many of the complications encountered are the same as those seen in conventional laparoscopy; however, there are a number of potential problems specific to robotic surgery that the pediatric urologist must be able to both anticipate and manage in order to minimize the risk of utilizing this novel surgical tool. The chapter summarizes the potential for and management of these complications.

Negative pressure pulmonary edema after laparoscopic donor nephrectomy.

Although usually a self-limiting phenomenon, negative pressure pulmonary edema requires immediate re-establishment of the airway, adequate oxygenation, and application of a positive airway.

Risk stratification and early oncologic outcomes following robotic prostatectomy.

Results of this study suggest that robotic prostatectomy provides good cancer outcomes for clinically localized disease.

Müllerian remnant malignancy.

Mixed gonadal dysgenesis is a disorder of sexual differentiation, characterized by mosaicism, ambiguous external genitalia, and both Wolffian and Müllerian internal genitalia. These patients are at a known increased risk of germ cell cancer, specifically gonadoblastoma; however, in this report we describe a case of adenocarcinoma of a remnant Müllerian structure.