Background-The remodeled vessel wall in many vascular diseases such as restenosis after injury is characterized by proliferative and apoptosis-resistant vascular smooth muscle cells. There is evidence that proproliferative and antiapoptotic states are characterized by a metabolic (glycolytic phenotype and hyperpolarized mitochondria) and electric (downregulation and inhibition of plasmalemmal K ϩ channels) remodeling that involves activation of the Akt pathway. Dehydroepiandrosterone (DHEA) is a naturally occurring and clinically used steroid known to inhibit the Akt axis in cancer. We hypothesized that DHEA will prevent and reverse the remodeling that follows vascular injury. Methods and Results-We used cultured human carotid vascular smooth muscle cell and saphenous vein grafts in tissue culture, stimulated by platelet-derived growth factor to induce proliferation in vitro and the rat carotid injury model in vivo. DHEA decreased proliferation and increased vascular smooth muscle cell apoptosis in vitro and in vivo, reducing vascular remodeling while sparing healthy tissues after oral intake. Using pharmacological (agonists and antagonists of Akt and its downstream target glycogen-synthase-kinase-3␤ [GSK-3␤]) and molecular (forced expression of constitutively active Akt1) approaches, we showed that the effects of DHEA were mediated by inhibition of Akt and subsequent activation of GSK-3␤, leading to mitochondrial depolarization, increased reactive oxygen species, activation of redox-sensitive plasmalemmal voltage-gated K ϩ channels, and decreased [Ca 2ϩ ] i . These functional changes were accompanied by sustained molecular effects toward the same direction; by decreasing [Ca 2ϩ ] i and inhibiting GSK-3␤, DHEA inhibited the nuclear factor of activated T cells transcription factor, thus increasing expression of Kv channels (Kv1.5) and contributing to sustained mitochondrial depolarization. These results were independent of any steroidrelated effects because they were not altered by androgen and estrogen inhibitors but involved a membrane G protein-coupled receptor. Conclusions-We suggest that the orally available DHEA might be an attractive candidate for the treatment of systemic vascular remodeling, including restenosis, and we propose a novel mechanism of action for this important hormone and

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Context.—Diagnostic use of immunohistochemistry has been extensively studied in prostate needle biopsy, but its use in routine practice and the quality assurance and associated cost have not been previously addressed. Objective.—To examine the routine use of immunohistochemistry in prostate biopsies in a tertiary academic institution. Design.—We reviewed reports of 748 consecutive prostate biopsies and we evaluated the turnaround times, the final diagnosis on individual specimens, the intradepartmental consultation rates, and the associated costs. Results.—Immunohistochemistry evaluation was required for 39.4% of biopsies and 12% of blocks (average 1.8 blocks/case). The biopsies with immunohistochemistry were signed out 1.7 workdays later (8.6 versus 6.9 days). The diagnostic breakdown for individual blocks evaluated by immunohistochemistry was Cancer 47.7%; Atypical, Suspicious 10.8%; Small Atypical Glands Adjacent to High-Grade Prostatic Intraepithelial Neoplasia 6.9%; High-Grade Prostatic Intraepithelial Neoplasia 12.4%; and Benign 22.2%. Diagnoses of Cancer or Atypical, Suspicious (Atypical, Suspicious + Small Atypical Glands Adjacent to High-Grade Prostatic Intraepithelial Neoplasia) were rendered in 65.4% of individual blocks assessed by immunohistochemistry. Immunohistochemistry aided in establishing limited cancer (≤10% of core) in 69.3% of cases and in 74% of single-core–positive biopsies. Departmental consultation was performed in 18.3% of biopsies and immunohistochemistry was used in 68% of these cases. Both immunohistochemistry and consultation were performed in 55.8% of Atypical, Suspicious cases. The average immunohistochemistry cost per biopsy was $22.34 and the estimated annual cost for prostate biopsy immunohistochemistry in our laboratory was $33 420.64. Conclusions.—Immunohistochemistry is frequently used in our prostate biopsy practice to establish or confirm a limited Cancer diagnosis, to better resolve diagnostic ambiguity, or for quality assurance. The data provided herein can be used for comparisons with other prostate biopsy practices.