Statin use and fatal prostate cancer: a matched case-control study.

BACKGROUND: Statins are some of the most commonly prescribed medications in medical practice, and prostate cancer is the most common malignancy among men. Although there has been no consistent evidence that statins affect cancer incidence, including prostate cancer, several reports suggest they may decrease the rate of advanced prostate cancer. However, no study to date has specifically examined statin use and prostate cancer mortality. The authors conducted this population-based case-control investigation to examine this association. METHODS: This was a matched case-control study. Cases were residents of New Jersey ages 55 to 79 years who died from prostate cancer between 1997 and 2000. The cases were matched individually to population-based controls by 5-year age group and race. Medication data were obtained identically for cases and controls from blinded medical chart review. Conditional logistic regression was used to adjust for confounders. RESULTS: In total, 718 cases were identified, and cooperation was obtained from 77% of their spouses (N = 553). After a review of medical records, 387 men were eligible, and 380 were matched to a control. The unadjusted odds ratio was 0.49 (95% confidence interval, 0.34-0.70) and decreased to 0.37 (P < .0001) after adjusting for education, waist size, body mass index, comorbidities, and antihypertensive medication. There was little difference between lipophilic and hydrophilic statins, but more risk reduction was noted for high-potency statins (73%; P < .0001) compared with low-potency statins (31%; P = .32). CONCLUSIONS: Statin use was associated with substantial protection against prostate cancer death, adding to the epidemiologic evidence for an inhibitory effect on prostate cancer.

Angular domain transillumination imaging optimization with an ultrafast gated camera.

By employing high-aspect-ratio parallel microchannels as an angular filter, quasiballistic photons sensitive to internal structures in a turbid medium can be captured. Scattered photons exiting the turbid medium typically exhibit trajectories with random angles compared to the initial trajectory and are mostly rejected by the filter. However, angular filter arrays cannot differentiate between quasiballistic photons (early arriving) and photons that happen to attain a scattered trajectory that is within the acceptance angle (late arriving). Therefore, we have two objectives: (1) to experimentally characterize the angular distribution and proportion of minimally deviated quasiballistic photons and multiply scattered photons in a turbid medium and (2) to combine time and angular gating principles so that early and late arriving photons can be distinguished. From the angular distribution data, the angular filter with angular acceptance about 0.4 deg yields the highest image contrast for transillumination images. The use of angular domain imaging(ADI) with time-gating enables visualization of submillimeter absorbing objects with approximately seven times higher image contrast compared to ADI in a turbid medium with a scattering level of six times the reduced mean free path.

Transmission and fluorescence angular domain optical projection tomography of turbid media.

When imaging through turbid media, objects are often blurred by scattered light. An optical collimator (i.e., an angular filter array) improves images by accepting only photons propagating within a narrow solid angle about the direction of the incident light. These photons are expected to participate in a limited number of small-angle scattering events, maintaining their original propagation direction and, finally, contributing to the development of a faithful image of an object within a turbid medium. The collimation method, also referred to as angular domain imaging (ADI), applies to a see-through configuration where the incident collimated light beam can be aligned with the collimator in a transillumination mode of operation. In this paper, we present angular domain optical projection tomography (ADOPT), a method that can extract depth information of optical contrast in turbid media with high longitudinal resolution based on ADI technology. The resolution of the ADI system has been tested over various depths in a 5 cm optical cuvette using a resolution target suspended in a homogeneous turbid medium. The ADOPT system reconstructed images from a series of angular domain projections collected at angular intervals. The system was used to measure the attenuation of an absorbing target in transmission mode (t-ADOPT) and to measure the light emitting from a fluorescent target (f-ADOPT). Tissue-mimicking phantoms were used to validate the performance of the method. In the t-ADOPT configuration, a background scattered light estimation and subtraction methodology was introduced to improve the imaging contrast. A target consisting of two graphite rods (0.9 mm diameter) was suspended in the cuvette by a rotation stage. An Indocyanine Green-filled glass rod was used as an imaging target in the f-ADOPT arrangement. The target was placed in a manner such that the line of laser light was perpendicular to the longitudinal axis of the rods. Several projections were collected at increments of 1.8 degrees and compiled into a sinogram. A transverse image was reconstructed from the sinogram by using filtered backprojection and image contrast was improved by experimental scatter measurements using a wedge prism and an image processing algorithm. The submillimeter target embedded in a 2 cm thick scattering medium (reduced scattering coefficient < or = 2.4 cm(-1)) was discernable in both the sinograms and the reconstructed images. In the f-ADOPT system, fluorescent line targets <1 cm in diameter embedded in a 2 cm thick scattering medium (reduced scattering coefficient < or = 0.8 cm(-1)) were discernable in both the sinograms and the reconstructed images. The proposed method could be used as the basis to construct an optical tomographic scanner for simultaneous absorption and fluorescence-based imaging of biological specimens (i.e., up to 7 mm across).

Endothelial rehabilitation: the impact of chronic PDE5 inhibitors on erectile function and protein alterations in cavernous tissue of diabetic rats.

BACKGROUND: Diabetic men generally have reduced efficacy with PDE-5 inhibitors (PDE5i) for the treatment of erectile dysfunction (ED). OBJECTIVE: To determine whether chronic vardenafil exposure alters cavernous protein expression predicting improved erectile function in diabetes. DESIGN: Forty-two adult male Sprague Dawley rats with streptozotocin-induced (50mg/kg IP) diabetes for 4 wk, were exposed to either vehicle or vardenafil for 6 wk. Assessments compared the impact of vardenafil given at 1h and 20 h to erectile function and cellular alterations and downstream translation of cavernous protein profiles were aimed. INTERVENTION: Vehicle or vardenafil 0.5mg/kg/day by oral gavage for 6 wk. MEASUREMENTS: Erectile function, penile tissue morphology, protein expression and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI) protein profiling were determined. RESULTS AND LIMITATIONS: A significant increase of intracavernous pressure was seen in both treatment arms compared to diabetic rats not receiving vardenafil. Immunohistochemical staining showed improved endothelial and smooth muscle cell staining with chronic vardenafil use. Western blot analysis demonstrated increased endothelial cell eNOS and smooth muscle alpha-actin protein content. SELDI protein profiling showed enhanced proteins expression at molecular weights of 14.7, 20, 41.9, 66.2, and 83.9 kDa in the chronically treated vardenafil group. CONCLUSIONS: Vardenafil was effective in treating diabetic-induced ED with the greatest effect achieved through chronic dosing, with no additive effect measured with the final acute dose. Changes noted in the histology and protein expression indicate that vardenafil may have a protective effect in this disease state. This finding may serve as a basis for further work evaluating the utility of chronic vardenafil dosing in diabetic men.

ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism.

The mitotic kinesin KSP (kinesin spindle protein, or Eg5) has an essential role in centrosome separation and formation of the bipolar mitotic spindle. Its exclusive involvement in the mitotic spindle of proliferating cells presents an opportunity for developing new anticancer agents with reduced side effects relative to antimitotics that target tubulin. Ispinesib is an allosteric small-molecule KSP inhibitor in phase 2 clinical trials. Mutations that attenuate ispinesib binding to KSP have been identified, which highlights the need for inhibitors that target different binding sites. We describe a new class of selective KSP inhibitors that are active against ispinesib-resistant forms of KSP. These ATP-competitive KSP inhibitors do not bind in the nucleotide binding pocket. Cumulative data from generation of resistant cells, site-directed mutagenesis and photo-affinity labeling suggest that they compete with ATP binding via a novel allosteric mechanism.