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Oral fluid (OF) offers a simple, non-invasive, directly observable sample collection for clinical and forensic drug testing. Given that chronic cannabis smokers often engage in drug administration multiple times daily, evaluating OF cannabinoid pharmacokinetics during ad libitum smoking is important for practical development of analytical methods and informed interpretation of test results. Eleven cannabis smokers resided in a closed research unit for 51 days, and underwent four, 5-day oral delta-9-tetrahydrocannabinol (THC) treatments. Each medication period was separated by 9 days of ad libitum cannabis smoking from 12:00 to 23:00 h daily. Ten OF samples were collected from 9:00-22:00 h on each of the last ad libitum smoking days (Study Days 4, 18, 32, and 46). As the number of cannabis cigarettes smoked increased over the study days, OF THC, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) also increased with a significant effect of time since last smoking (Δtime; range, 0.0-17.4 h) and ≥88% detection rates; concentrations on Day 4 were significantly lower than those on Days 32 and 46 but not Day 18. Within 30 min of smoking, median THC, CBN, and THCCOOH concentrations were 689 µg/L, 116 µg/L, and 147 ng/L, respectively, decreasing to 19.4 µg/L, 2.4 µg/L, and 87.6 ng/L after 10 h. Cannabidiol and 11-hydroxy-THC showed overall lower detection rates of 29 and 8.6%, respectively. Cannabinoid disposition in OF was highly influenced by Δtime and composition of smoked cannabis. Furthermore, cannabinoid OF concentrations increased over ad libitum smoking days, in parallel with increased cannabis self-administration, possibly reflecting development of increased cannabis tolerance. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: The plastic used in many medical devices is composed primarily of the plastic polyvinyl chloride (PVC). PVC is made flexible by treating it with chemical compounds called plasticizers. The most commonly used plasticizer is di(2-ethylhexyl) phthalate (DEHP). The general population is exposed daily to DEHP and one of its many metabolites, mono(2-ethylhexyl) phthalate (MEHP), primarily through food and aerosolization of environmental exposure. Exposure rises dramatically in premature or ill neonates, who are exposed to medical devices including enteral, blood and infusion bags, tubes and infusion devices. The rate of leaching of DEHP depends on many factors, including contact with lipophilic solutions and the amount of DEHP found in the product. Highly lipophilic substances readily extract plasticizers from PVC bags and tubes. Our objective was to determine the concentration of DEHP and MEHP in the urine of infants undergoing extracorporeal membrane oxygenation (ECMO) and near-miss ECMO to determine if ECMO results in increased concentrations of DEHP and MEHP in the urine. Study design: Using an in vivo prospective comparative study design, we evaluated 12 term or near-term neonates requiring ECMO. Our control population included 17 neonates with similar underlying diagnoses, referred to our NICU for ECMO but who ultimately responded to maximal medical therapy without ECMO. Two baseline urine samples were collected on admission to the NICU for DEHP and MEHP analysis on both the ECMO and near-miss populations. Daily urine samples were collected sequentially for five days in both populations. Urine samples were collected prior to discharge/transfer for both populations. Urinary DEHP and MEHP analysis was performed using tandem mass spectroscopy. Demographic data was collected for each patient. Results: We enrolled a total of twenty-nine patients in the study. All patients were transported to our NICU from outside birthing centers. Twelve neonates required ECMO support. The other seventeen patients responded to maximal medical therapy without ECMO. The mean DEHP for the ECMO group was 38.0 (95% CI=29.6, 47.5) compared to 33.0 (95% CI = 26.6, 40.1) in the near-miss group. The mean MEHP for the ECMO group was 29.8 (95% CI=22.4, 38.2) compared to 26.1 (95% CI=20.6, 32.3) for the near-miss group. Conclusion: Even though urinary levels of DEHP and MEHP were slightly higher in the ECMO group compared to the near-miss group, these differences were not statistically significant. [ABSTRACT FROM AUTHOR]

Ewing sarcoma family of tumors (ESFT) is a group of aggressive pediatric malignancies driven by the EWS-FLI1 fusion protein, an aberrant transcription factor up-regulating specific target genes, such as neuropeptide Y (NPY) and its Y1 and Y5 receptors (Y5Rs). Previously, we have shown that both exogenous NPY and endogenous NPY stimulate ESFT cell death via its Y1 and Y5Rs. Here, we demonstrate that this effect is prevented by dipeptidyl peptidases (DPPs), which cleave NPY to its shorter form, NPY3-36, not active at Y1Rs. We have shown that NPY-induced cell death can be abolished by overexpression of DPPs and enhanced by their down-regulation. Both NPY treatment and DPP blockade activated the same cell death pathway mediated by poly(ADP-ribose) polymerase (PARP-1) and apoptosis-inducing factor (AIF). Moreover, the decrease in cell survival induced by DPP inhibition was blocked by Y1 and Y5R antagonists, confirming its dependence on endogenous NPY. Interestingly, similar levels of NPY-driven cell death were achieved by blocking membrane DPPIV and cytosolic DPP8 and DPP9. Thus, this is the first evidence of these intracellular DPPs cleaving releasable peptides, such as NPY, in live cells. In contrast, another membrane DPP, fibroblast activation protein (FAP), did not affect NPY actions. In conclusion, DPPs act as survival factors for ESFT cells and protect them from cell death induced by endogenous NPY. This is the first demonstration that intracellular DPPs are involved in regulation of ESFT growth and may become potential therapeutic targets for these tumors. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cyclosporine (CsA) monitoring is essential for transplant success. We report a performance study of the recently released, fully automated Siemens ADVIA Centaur® CsA assay. Methods: Whole blood samples from 248 transplant patients were prepared using a new 1-step extraction method. Performance evaluations vs. HPLC–tandem MS (LC-MS/MS), Abbott TDx and AxSYM assays were conducted according to CLSI EP5-A2 and EP9-A2 guidelines. Results: The correlation coefficient for LC-MS/MS and ADVIA Centaur was≥0.97 at each site, and for each transplant type. Regression analysis yielded y =0.94x +19 for all sites: 95% CI=0.91–0.96 (slope) and 10–28 (intercept). Absolute and relative bias was minimal for C0 and C2 sampling. Centaur vs. Abbott TDx and AxSYM assays: y = 0.72x +6, r = 0.98, 95% CI = 0.70–0.73 (slope), 3–9 (intercept); and y = 0.69x +18, r = 0.97, 95% CI = 0.67–0.71 (slope), 8–27(intercept). Within run CVs were 4.5%–7.1%, total CVs were 5.3%–7.7%. Conclusions: The ADVIA Centaur assay compared favorably with LC-MS/MS and Abbott assays, displaying good correlation for all transplant types and methods. [Copyright &y& Elsevier]

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Mount Sinai has licensed serological assays to commercial entities and has filed for patent protection for serological assays. Daniel Stadlbauer and Florian Krammer are listed as inventors on the pending patent application. No other potential conflicts of interest were disclosed.