Pseudopterosin A (PsA) treatment of growth factor depleted human umbilical vein endothelial cell (HUVEC) cultures formulated in hydroxypropyl-β-cyclodextrin (HPβCD) for 42 h unexpectedly produced a 25% increase in cell proliferation (EC50 = 1.34 × 10−8 M). Analysis of dose response curves revealed pseudo-first order saturation kinetics, and the uncoupling of cytotoxicity from cell proliferation, thereby resulting in a widening of the therapeutic index. The formulation of PsA into HPβCD produced a 200-fold increase in potency over a DMSO formulation; we propose this could result from a constrained presentation of PsA to the receptor, which would limit non-specific binding. These results support the hypothesis that the non-specific receptor binding of PsA when formulated in DMSO has ostensibly masked prior estimates of specific activity, potency, and mechanism. Collectively, these results suggest that the formulation of PsA and compounds of similar chemical properties in HPβCD could result in significant pharmacological findings that may otherwise be obscured when using solvents such as DMSO.
Introduction: Smoking cessation treatment combining medication and counselling yields the best outcomes; however, few smokers employ both modalities.Aims: The purpose of this study was to examine variables predicting treatment attendance.Methods: This was a chart review of US military Veterans (N = 340; 89% male, 59% non-Hispanic white) referred for smoking cessation, who completed a telephone call to encourage treatment utilization. Treatment engagement was defined as attending a smoking cessation session within 30 days following telephone contact. A logistic regression analysis examined predictors (demographics, smoking variables, and psychiatric diagnoses) of treatment engagement.Results/Findings: Greater age (Odds Ratio [OR] = 1.04, 95% confidence interval [CI] 1.01–1.06), more cigarettes (OR = 1.03, 95% CI 1.00–1.06), and higher perceived importance of quitting (OR = 1.11, 95% CI 1.00–1.23) predicted engaging in treatment within 30 days (all p values < 0.05).Conclusion: Veterans who attended treatment were older, smoked more cigarettes, and perceived quitting as more important than those who did not attend. These findings are consistent with prior studies examining factors associated with treatment utilization. Results highlight the need to identify strategies for engaging into treatment smokers who are younger, smoke fewer cigarettes, and view quitting as less important.
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