Critical research gaps in electronic cigarette devices and nicotine aerosols.

Electronic cigarettes (e-cigs) are devices that aerosolize nicotine-containing liquids for delivery as an inhaled vapor. E-cigs are currently marketed as smoking cessation devices, though the emergence and rapid adoption of these devices in recent years has sparked a great deal of concern over their safety. Given the plethora of devices and nicotine solutions available on the market and the lack of regulation and quality control, it is imperative that these devices and nicotine formulations are studied to assess critical operating parameters, the pharmacokinetic profiles of the inhaled nicotine, and the toxicity profiles of the e-cig aerosols.

Time Course Expression Analysis of 1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole Induction of Cytoprotection in Human Endothelial Cells.

1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), a synthetic derivative of oleanolic acid that exhibits antioxidant and anti-inflammatory activity in several animal and in vitro models, has been shown to be beneficial if given after injury. Although induction of heme oxygenase 1 appears to be a major effector of cytoprotection, the mechanism by which the overall effect is mediated is largely unknown. This study evaluated temporal gene expression profiles to better characterize the early transcriptional events and their relationship to the dynamics of the cytoprotective response in human umbilical vein endothelial cells (HUVEC) to CDDO-Im.

Cytoprotection of human endothelial cells from oxidant stress with CDDO derivatives: network analysis of genes responsible for cytoprotection.

Aim: To identify drugs that may reduce the impact of oxidant stress on cell viability.

Methods: Human umbilical vein endothelial cells were treated with 200 nmol/l CDDO-Im (imidazole) and CDDO-Me (methyl) after exposure to menadione and compared to vehicle-treated cells. Cell viability and cytotoxicity were assessed, and gene expression profiling was performed.

The use of BDDCS in classifying the permeability of marketed drugs.

We recommend that regulatory agencies add the extent of drug metabolism (i.e., >or=90% metabolized) as an alternate method in defining Class 1 marketed drugs suitable for a waiver of in vivo studies of bioequivalence.

Molecular properties of WHO essential drugs and provisional biopharmaceutical classification.

The purpose of this study is to provisionally classify, based on the Biopharmaceutics Classification System (BCS), drugs in immediate-release dosage forms that appear on the World Health Organization (WHO) Essential Drug List. The classification in this report is based on the aqueous solubility of the drugs reported in commonly available reference literature and a correlation of human intestinal membrane permeability for a set of 29 reference drugs with their calculated partition coefficients. The WHO Essential Drug List consists of a total of 325 medicines and 260 drugs, of which 123 are oral drugs in immediate-release (IR) products.

Effect of interleukin-1beta and tumor necrosis factor-alpha on gene expression in human endothelial cells.

Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are two major cytokines that rise to relatively high levels during systemic inflammation, and the endothelial cell (EC) response to these cytokines may explain some of the dysfunction that occurs. To better understand the cytokine-induced responses of EC at the gene expression level, human umbilical vein EC were exposed to IL-1beta or TNF-alpha for various times and subjected to cDNA microarray analyses to study alterations in their mRNA expression. Of approximately 4,000 genes on the microarray, expression levels of 33 and 58 genes appeared to be affected by treatment with IL-1beta and TNF-alpha, respectively; 25 of these genes responded to both treatments.