The Role of Compensation in Nicotine Reduction.

The available research on switching from normal nicotine to very low nicotine content cigarettes shows minimal evidence of compensatory smoking. Mathematical estimations suggest that substantial compensation after switching to very low nicotine cigarettes would be impossible. It is likely that smokers who are unable to tolerate the extent of proposed nicotine reduction would switch to other sources of nicotine, rather than try to compensate by smoking more very low nicotine content cigarettes more intensely

Developmental Effects of Nicotine Exposure in Drosophila Melanogaster

Approximately 12%-20% of pregnant women smoke at some point during pregnancy, and 10% of pregnant women are reported to have smoked during the last 3 months of pregnancy. Smoking during pregnancy leads to developmental health risks for the fetus and child, including increased mortality, low birth weight, and developmental delays. The direct molecular targets of nicotine are nicotinic acetylcholine receptors (nAChRs) due to the similarities in structure between nicotine and acetylcholine. However, in many cases, it remains unclear what molecular events downstream of nAChRs lead to the deleterious effects of nicotine on development. We have established Drosophila melanogaster as a genetic model system to study the developmental effects of nicotine. So far, we have established that nicotine reduces survival and increases development time in a dose-responsive manner. In addition, we have evidence that developmental nicotine exposure may reduce adult body weight, and that ethanol and nicotine act in a non-additive fashion to reduce survival. Finally, we show that nicotine exposure does not appear to affect brain size in developing larvae. Our results show that the effects of nicotine on fly development are similar to those seen in mammals, and establish Drosophila as a model organism for the study of the deleterious effects of nicotine on development

Using EGA-GC to Analyze Nicotine N-oxide in Order to Explain Low Nicotine Concentrations in E-cigarette Liquids

Evolved-gas analysis coupled with gas chromatography (EGA-GC) was used to analyze e-cigarette liquids. Previous analyses of e-cigarette liquids have shown that the determined concentration of nicotine is lower than the advertised concentration. A possible explanation for this phenomenon is that the nicotine in the liquids is being oxidized to nicotine N-oxide by exposure to air and thus reducing the concentration of nicotine. This study focused on analyzing samples of thermally-rearranged nicotine N-oxide. Using EGA-GC, a calibration curve was generated for nicotine N-oxide concentration, which could potentially be used to explain reduced nicotine concentrations in e-cigarette liquids

Comparative cytotoxicity study of nicotine and cotinine on MRC-5 cell line

Nicotine has several health hazards regarding carcinogenic potential. It also imparts increased risk for respiratory, cardiovascular, and gastrointestinal disorders. Several mechanisms have been proposed for the carcinogenic potential, including effects on cell proliferation, inducing oxidative stress, DNA mutation, or inhibition of apoptosis. The cotinine metabolite is generally thought to have effects similar to nicotine in some experimental systems. The purpose of this study was to assess the nicotine and cotinine cytotoxicity on MRC-5 lung fibroblasts. The pulmonary fibroblasts were treated with various concentrations of nicotine or cotinine (in the range 1 µM – 2 mM) for 24 or 48 h and analyzed for cell viability by MTT test. The results indicated that high nicotine concentrations (2 mM) induced marked cell death (about 50%) in MRC-5 cell line. Cotinine showed lower toxicity than nicotine on the MRC-5 cells. In contrast to nicotine treatment, cells treated with cotinine continued to proliferate after the 48h incubation period

Nicotine strongly activates dendritic cell-mediated adaptive immunity - potential role for progression of atherosclerotic lesions

Background - Antigen-presenting cells (APCs) such as monocytes and dendritic cells (DCs) stimulate T-cell proliferation and activation in the course of adaptive immunity. This cellular interaction plays a role in the growth of atherosclerotic plaques. Nicotine has been shown to increase the growth of atherosclerotic lesions. Therefore, we investigated whether nicotine can stimulate APCs and their T cell–stimulatory capacity using human monocyte–derived DCs and murine bone marrow–derived DCs as APCs. Methods and Results - Nicotine dose-dependently (10-8 to 10-4 mol/L) induced DC expression of costimulatory molecules (ie, CD86, CD40), MHC class II, and adhesion molecules (ie, LFA-1, CD54). Moreover, nicotine induced a 7.0-fold increase in secretion of the proinflammatory TH1 cytokine interleukin-12 by human DCs. These effects were abrogated by the nicotinic receptor antagonist -bungarotoxin and mecamylamine, respectively. The effects of nicotine were mediated in part by the phosphorylation of the PI3 kinase downstream target Akt and the mitogen-activated kinases ERK and p38 MAPK. Nicotine-stimulated APCs had a greater capacity to stimulate T-cell proliferation and cytokine secretion, as documented by mixed lymphocyte reactions and ovalbumin-specific assays with ovalbumin-transgenic DO10.11 mice. In a murine model of atherosclerosis, nicotine significantly enhanced the recruitment of DCs to atherosclerotic lesions in vivo. Conclusions - Nicotine activates DCs and augments their capacity to stimulate T-cell proliferation and cytokine secretion. These effects of nicotine may contribute to its influence on the progression of atherosclerotic lesions