Intragastric nicotine protects against 40% ethanol-induced gastric mucosal injury despite pretreatment with propranolol orN-ethylmaleimide in rats

We tested the hypotheses that the protective effect of intragastric nicotine against ethanol-induced gastric mucosal injury is dependent on propranolol- orN-ethylmaleimide-sensitive mechanisms. Propranolol was administered in doses (2 and 20 mg/kg) that provided dose-related blockade of -adrenoceptors (significant decreases in heart rate).N-Ethylmaleimide was administered in doses that previously had been shown to increase gastric vascular permeability (10 mg/kg) or inhibit gastric mucosal sulfhydryl compounds (50 mg/kg). At 0.5 hr after these or control subcutaneous pretreatments, the rats received intragastric nicotine (4 mg/kg) or vehicle. One hour later 40% ethanol was given intragastrically. The gastric corpus mucosal lesions were recorded by polaroid photographs after another hour, and their areas measured unbiasedly by computerized image analysis. The results showed thatN-ethylmaleimide, but not propranolol, aggravated ethanol-induced gastric mucosal injury. The protective effect of intragastric nicotine was not modified by either pretreatment. We conclude that the mechanism mediating intragastric nicotine protection against 40% ethanol-induced gastric mucosal injury is independent of propranolol- orN-ethylmaleimide-sensitive mechanisms.Supported by Veterans Administration Medical Research Funds, and in part by research grants (0162-01, 02 and 0291-01) from the Smokeless Tobacco Research Council, Inc., and by funds (1RT 80) provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco-Related Disease Research Program of the University of California to FWL. Dr. Endoh is a recipient of the University of California Tobacco-Related Disease Research Program Research Fellowship Award (FT 37).     

Comparative dynamics of four smoking withdrawal symptom scales

Aims To examine the association of person‐specific trajectories of withdrawal symptoms of urge‐to‐smoke, negative affect, physical symptoms and hunger during the first 7 days after smoking cessation with abstinence at end of treatment (EOT) and at 6 months. Design Hierarchical linear modeling (HLM) was used to model person‐specific trajectory parameters (level, slope, curvature and volatility) for withdrawal symptoms. Setting University‐based smoking cessation trials. Participants Treatment‐seeking smokers in clinical trials of transdermal nicotine versus nicotine spray (n = 514) and bupropion versus placebo (n = 421). Measurements Self‐reported withdrawal symptoms for 7 days after the planned quit date, and 7‐day point prevalence and continuous abstinence at EOT and 6 months. Findings In regressions that included trajectory parameters for one group of withdrawal symptoms, both urge‐to‐smoke and negative affect were predictive of abstinence while physical symptoms and hunger were generally not predictive. In stepwise regressions that included the complete set of trajectory parameters across withdrawal symptoms (for urge‐to‐smoke, negative affect, physical symptoms and hunger), with a single exception only the trajectory parameters for urge‐to‐smoke were predictive. Area under the receiver operator characteristic curve was 0.594 for covariates alone, and 0.670 for covariates plus urge‐to‐smoke trajectory parameters. Conclusions Among a number of different withdrawal symptoms (urge‐to‐smoke, negative affect, physical symptoms and hunger) urge‐to‐smoke trajectory parameters (level, slope and volatility) over the first 7 days of smoking cessation show the strongest prediction of both short‐ and long‐term relapse. Other withdrawal symptoms increase the predictive ability by negligible amounts.     

DSM criteria for tobacco use disorder and tobacco withdrawal: a critique and proposed revisions for DSM-5

Aims This paper aims to identify appropriate criteria for tobacco dependence assessment, evaluate relevant research and suggest revisions that may be incorporated into DSM‐5. Methods Desirable conceptual and psychometric features of tobacco dependence assessments were identified, including the types of outcomes against which such assessment should be validated. DSM‐IV criteria were matched against these criteria and compared with other dependence measures. Results DSM‐IV criteria were found to be ambiguous, little used in tobacco research, and have relatively low predictive validity. Other dependence measures were found to have greater validity in the prediction of important dependence features such as relapse likelihood. Strength of urges to smoke on typical smoking days and during abstinence, markers of nicotine intake or frequency of smoking and latency to smoke soon after waking were found to be useful dependence measures. Conclusion The use and utility of DSM‐5 will be enhanced by eliminating most DSM‐IV criteria and adding new ones based on smoking pattern, smoking heaviness, and the severity of craving during periods of smoking and withdrawal.     

Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E(2) by hypoxia-inducible factor-1α up-regulation in human periodontal ligament cells

Kim Y‐S, Shin S‐I, Kang K‐L, Herr Y, Bae W‐J, Kim E‐C. Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E₂ by hypoxia‐inducible factor‐1α up‐regulation in human periodontal ligament cells. J Periodont Res 2012; 47: 719–728. © 2012 John Wiley & Sons A/S Background and Objective: Although hypoxia‐inducible factor 1α (HIF‐1α) is up‐regulated in the periodontal pockets of periodontitis patients, the expression and precise molecular mechanisms of HIF‐1α remain unknown in human periodontal ligament cells (PDLCs). The aim of this study was to explore the effects, as well as the signaling pathway, of nicotine and lipopolysaccharide (LPS) on the expression of HIF‐1α and on the production of its target genes, including cyclooxygenase‐2 (COX‐2)‐derived prostaglandin E₂ (PGE₂), MMP‐2 and MMP‐9 in PDLCs. Material and Methods: The expression of COX‐2 and HIF‐1α proteins was evaluated using western blotting. The production of PGE₂ and MMPs was evaluated using enzyme immunoassays and zymography, respectively. Results: LPS and nicotine synergistically induced the production of PGE₂, MMP‐2 and MMP‐9, and increased the expression of MMP‐2, MMP‐9, COX‐2 and HIF‐1α proteins. Inhibition of HIF‐1α activity by chetomin or knockdown of HIF1α gene expression by small interfering RNA markedly attenuated the production of LPS‐ and nicotine‐stimulated PGE₂ and MMPs, as well as the expression of COX‐2 and HIF‐1α. Furthermore, pretreatment with inhibitors of COX‐2, p38, extracellular signal‐regulated kinase, Jun N‐terminal kinase, protein kinase C, phosphatidylinositol 3‐kinase and nuclear factor‐kappaB decreased the expression of nicotine‐ and LPS‐induced HIF‐1α and COX‐2, as well as the activity of PGE₂ and MMPs. Conclusion: These data demonstrate novel mechanisms by which nicotine and LPS promote periodontal tissue destruction, and provide further evidence that HIF‐1α is a potential target in periodontal disease associated with smoking and dental plaque.     

The epigenetic effect of nicotine on dopamine D1 receptor expression in rat prefrontal cortex

Nicotine is a highly addictive drug and exerts its effect partially through causing dopamine release, thereby increasing intrasynaptic dopamine levels in the brain reward systems. Dopaine D1 receptor (DRD1) mRNAs and receptors are localized in reward‐related brain regions, which receive cholinergic input. The aim of this study is to evaluate whether nicotine administration affects the expression of DRD1s, and if so, whether epigenetic mechanisms, such as histone acetylation, are involved. Twenty Male Sprague Dawley rats received nicotine (0.4 mg/kg/day, s.c.) or saline injections for 15 days. After nicotine/saline treatment, rats were perfused with saline; prefrontal cortex (PFC), corpus striatum (STR), and ventral tegmental area (VTA) were dissected. Homogenates were divided into two parts for total RNA isolation and histone H4 acetylation studies. DRD1 mRNA expression was significantly higher in the PFC of the nicotine‐treated group compared with controls; similar trends were observed in the VTA and STR. To study epigenetic regulation, the 2kb upstream region of the DRD1 gene promoter was investigated for histone H4 acetylation in PFC samples. After chromatin immunoprecipitation with anti‐acetyl histone H4 antibody, we found an increase in histone acetylation by two different primer pairs which amplified the ?1365 to ?1202 (P < 0.005) and ?170 to +12 (P < 0.05) upstream regions of the DRD1 promoter. Our results suggest that intermittent subcutaneous nicotine administration increases the expression of DRD1 mRNA in the PFC of rats, and this increase may be due to changes in histone H4 acetylation of the 2kb promoter of the DRD1 gene. Synapse 67:545–552, 2013. © 2013 Wiley Periodicals, Inc.     

Could vaping help lower smoking rates in Australia?

In this brief article, we review the evidence on whether easier access to vaping could help lower smoking rates in Australia. To make a convincing case for vaping the following conditions need to be met: that vaping assists in smoking cessation; that the prevalence of vaping is high enough to produce measurable effects at a population level; and that the decline in smoking prevalence is slower in countries where vaping is less common. The evidence suggests that these criteria are satisfied.