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Cancer cells frequently exhibit resistance to the cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin also has been shown to enhance adenoviral transgene expression.', 'This study aims to evaluate the ability of cisplatin to enhance the expression and the cytotoxic effect of the tumor-specific adenoviral vector Ad/gTRAIL, which expresses a green fluorescent protein-TRAIL fusion protein.', 'Cultured cancer cells and normal human cells were infected with Ad/gTRAIL with or without cisplatin pretreatment. Adenoviral transgene expression was determined by using flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis enzyme-linked immunosorbent assay kit.', 'Green fluorescent protein-TRAIL fusion protein expression was significantly enhanced by cisplatin pretreatment in cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to 12-fold increase in green fluorescent protein fluorescence intensity across cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL-mediated cytotoxicity, as indicated by the drastic reduction of inhibitory concentration of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity noted in normal cells treated with both cisplatin and Ad/gTRAIL.
Does cisplatin enhance apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand?

Erectile dysfunction (ED) and atherosclerotic cardiovascular disease (ASCVD) share many common risk factors, and vascular ED is a marker for increased ASCVD risk. Low 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with increased ASCVD risk, but less is known regarding the relationship of low 25(OH)D with ED. We determined whether 25(OH)D deficiency is associated with ED independent of ASCVD risk factors.', 'We performed cross-sectional analyses of 3390 men aged ≥20 years free of ASCVD who participated in NHANES 2001-2004. Serum 25(OH)D was measured by the DiaSorin radioimmunoassay; deficiency was defined as levels <20\xa0ng/ml (<50\xa0nmol/L). Self-reported ED, assessed by a single validated question, was defined as men who reported being "never" or "sometimes able" to maintain an erection. We assessed the relationship between 25(OH)D deficiency and ED prevalence using adjusted Poisson regression methods.', 'After accounting for NHANES sampling, the weighted prevalence of 25(OH)D deficiency and of ED were 30% and 15.2%, respectively. 25(OH)D levels were lower in men with vs. those without ED (mean 22.8 vs 24.3\xa0ng/mL, respectively; p\xa0=\xa00.0005). After adjusting for lifestyle variables, comorbidities, and medication use, men with 25(OH)D deficiency had a higher prevalence of ED compared to those with levels ≥30\xa0ng/ml (Prevalence Ratio 1.30, 95% CI 1.08-1.57).
Is vitamin D deficiency independently associated with greater prevalence of erectile dysfunction : The National Health and Nutrition Examination Survey ( NHANES ) 2001-2004?

Maraviroc (MVC) is a potential candidate for 'on demand' preexposure prophylaxis. In the present study, we evaluated the efficacy of a single oral dose of MVC to prevent ex-vivo HIV-1 infection of rectal tissue in humans.", 'Eight HIV-1-negative healthy volunteers received a single oral dose of MVC (300 or 600\u200amg), and two additional volunteers received tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 300/200\u200amg) for 10 days. Rectal biopsies were performed prior to the ex-vivo challenge (day 0), at day 7 (4\u200ah after MVC) or after 10 days with TDF/FTC. Rectal biopsies were infected ex-vivo, and viral inhibition and CCR5 occupancy was analyzed. MVC concentration in plasma and rectal tissue was measured just after biopsy and after viral incubation.', 'Ex-vivo rectal tissue protection with MVC was incomplete in all but two participants, whereas TDF/FTC avoided ex-vivo infection in the two controls. Median dose-normalized concentration of MVC was significantly higher in rectal tissue than in plasma (561.1 and 155.1\u200ang/ml, respectively). A significant loss of MVC during the virus incubation (about 60%) and a low CCR5 occupancy (approximately 45%) were detected in rectal cells.

Does single oral dose of maraviroc prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers?