D,L-alpha-difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC) that is being investigated to treat cancers such as pediatric neuroblastoma. A novel and sensitive LC-MS/MS assay was developed and validated to quantify DFMO concentrations in support of pre-clinical pharmacokinetic studies in mice. The study was performed using a Shimadzu triple quad LC-MS/MS equipped with an Atlantis HILIC Silica 3 µm 2.1 × 100 mm column, and an isocratic mobile phase (75:25 acetonitrile and 0.2 % formic acid) at a flow rate of 0.5 mL/min. Multiple Reaction Monitoring (MRM) was used to identify the precursor ion (183 m/z) with quantification of daughter ions at transitions of 183 > 120.10, 183 > 166.10, and 183 > 80.05. Plasma standards and quality control samples (20 µL) were processed using protein precipitation with cold acetonitrile. The lower limit of detection (LLOQ) was 5 ng/mL. Assay performance was determined from multiple runs (n = 10) with standards ranging from 250-50,000 ng/mL and three levels of quality control (500, 4000, and 40,000 ng/mL). Standard curves were linear with r2 values between 0.9960 and 0.9999. Quality control samples were stable and exhibited maximum inter-day % bias of ≤3 % and CV% of ≤0.7 %. The assay was successfully applied to an in vivo study to determine the pharmacokinetics of DFMO in athymic nu/nu mice.

This study explored the in vivo performance of three oral ciprofloxacin formulations (oral solution, fast, or slow dissolving tablets) in beagle dogs. The in vivo absorption and dissolution behaviors, estimated with in silico mechanistic models, were compared to the results previously published in human volunteers. Six normal healthy male beagle dogs (five to completion) received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by tandem mass spectrometry detection. A mechanistic absorption model was used to predict the in vivo dissolution and absorption characteristics of the oral formulations. Canine ciprofloxacin absorption was constrained to the duodenum/jejunum. This absorption window was far narrower than that seen in humans. Furthermore, while substantial within-individual variability in drug absorption was seen in human subjects, a greater magnitude of variability was observed in dogs. For three sets of data, a lag time in gastric emptying was necessary to improve the accuracy of model-generated in vivo blood level profile predictions. In addition to species-associated dissimilarities in drug solubilization due to human versus canine differences in gastrointestinal fluid compositions, the far more rapid intestinal transit time and potential segmental differences in drug absorption needed to be considered during human-canine extrapolation of oral drug and drug product performance. Through the use of mechanistic models, the data generated in the human and canine studies contributed insights into some aspects of the interspecies differences to be considered when extrapolating oral bioavailability/formulation effect data between dogs and humans.

Objectives: To compare student academic performance from live and synchronous case-based active learning sessions between a satellite and main campus. The secondary objective was to evaluate student perception of instructional delivery methods.Methods: Students were taught infectious diseases through patient cases delivered either synchronously to both campuses or live at each campus. Student performance was assessed by examination grades. Student perception of content delivery methods was evaluated using a survey.Results: Students performed better on examinations that pertained to content that were delivered live. The average examination grade for live and synchronous course material was 72.2% and 62.2%, respectively. In the main campus, 81.5% of students preferred live lectures. In the satellite campus, 66.7% of students preferred synchronous education. Overall, students agreed that synchronous cases helped them prepare for graded assessments.Conclusions: Both campuses differed in their preference of instructional delivery methods. Though there was a higher examination score with the live cases, this could be due to the nature of the disease states tested and the small number of synchronously taught cases. Further evaluation of these delivery methods need to be done to confirm these results and to better utilize resources as multi-campus universities continue to grow. (C) 2013 Elsevier Inc. All rights reserved.

This 'Heart Health' program is an eight-week cycle with no exit date, providing flexibility in program attendance and delivery. Monthly all day sessions are conducted including guest speakers offering practical strategies to participants. Sessions are delivered by Aboriginal staff from DYHS and other organisations in collaboration with non Aboriginal health professionals (cardiac rehabilitation nurse, exercise physiologist, etc).

Aldosterone influences renal Na+ handling and normal blood pressure (BP) regulation but if consistently elevated, aldosterone may contribute to the development of hypertension. A few studies have found that as with BP, plasma aldosterone (PA) levels can change with aerobic exercise training (AEX) in hypertensives, but the response of these phenotypes to AEX vary by individual. The CYP11B2 (-344C/T) gene polymorphism has been associated with variability in both blood pressure and urinary and PA levels among hypertensives and may help explain the response of these phenotypes to AEX. The purpose of this study was to determine if the -344C/T polymorphism was associated with changes in PA levels, 24-hour Na+ excretion and BP after 6 months of AEX in middle-aged to older White prehypertensives. 23 Caucasian disease free, sedentary prehypertensives completed a standardized AEX program. All participants followed the AHA Step 1 diet. Blood samples were collected under fasting and supine conditions and PA was measured by RIA. The T and C allele frequencies were 0.61 and 0.39, respectively. There were 9 participants in the TT genotype group and 13 in the TC+CC genotype group. The TC+CC genotype group tended to decrease PA levels (−39±21 pg/ml, p=0.09) and had a greater reduction in PA levels with AEX than the TT genotype group after accounting for baseline plasma aldosterone levels (TC+CC −47±8 pg/ml; TT: −23±10 pg/ml, p<0.001). The TC+CC genotype group significantly decreased systolic BP (−4±2 pg/ml, p=0.03) and had a greater reduction in systolic BP with AEX than the TT genotype group after accounting for baseline systolic BP (TC+CC −4±1pg/ml; TT: −2±2 mm Hg, p<0.02). Neither genotype group changed diastolic BP or 24 hour Na+ excretion and there was no difference in the change in diastolic BP and 24-hour Na+ excretion between the two genotype groups. Based on this preliminary evidence, the presence of the C allele among prehypertensives is associated with a greater reduction in plasma aldosterone and systolic BP with AEX.