BackgroundCigarette smoking is a tough addiction to break. Therefore, improved approaches to smoking cessation are necessary. The electronic-cigarette (e-Cigarette), a battery-powered electronic nicotine delivery device (ENDD) resembling a cigarette, may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption. Efficacy and safety of these devices in long-term smoking cessation and/or smoking reduction studies have never been investigated.MethodsIn this prospective proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers (unwilling to quit) experimenting the 'Categoria' e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend a total of five study visits: at baseline, week-4, week-8, week-12 and week-24. Product use, number of cigarettes smoked, and exhaled carbon monoxide (eCO) levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.ResultsSustained 50% reduction in the number of cig/day at week-24 was shown in 13/40(32.5%) participants; their median of 25 cigs/day decreasing to 6 cigs/day (p < 0.001). Sustained 80% reduction was shown in 5/40(12.5%) participants; their median of 30 cigs/day decreasing to 3 cigs/day (p = 0.043). Sustained smoking abstinence at week-24 was observed in 9/40(22.5%) participants, with 6/9 still using the e-Cigarette by the end of the study. Combined sustained 50% reduction and smoking abstinence was shown in 22/40 (55%) participants, with an overall 88% fall in cigs/day. Mouth (20.6%) and throat (32.4%) irritation, and dry cough (32.4%) were common, but diminished substantially by week-24. Overall, 2 to 3 cartridges/day were used throughout the study. Participants' perception and acceptance of the product was good.ConclusionThe use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit (http://ClinicalTrials.gov number NCT01195597).
The need for novel and more effective approaches to tobacco control is unquestionable. The electronic cigarette is a battery-powered electronic nicotine delivery system that looks very similar to a conventional cigarette and is capable of emulating smoking, but without the combustion products accountable for smoking's damaging effects. Smokers who decide to switch to electronic cigarettes instead of continuing to smoke would achieve large health gains. The electronic cigarette is an emerging phenomenon that is becoming increasingly popular with smokers worldwide. Users report buying them to help quit smoking, to reduce cigarette consumption, to relieve tobacco withdrawal symptoms due to workplace smoking restrictions and to continue to have a 'smoking' experience but with reduced health risks. The focus of the present article is the health effects of using electronic cigarettes, with consideration given to the acceptability, safety and effectiveness of this product to serve as a long-term substitute for smoking or as a tool for smoking cessation.
Scavenger receptor class B, type I (SR-BI) binds HDL and mediates the selective uptake of cholesteryl esters (CE). Although the extracellular domain of SR-BI is critical for function, the structural characteristics of this region remain elusive. Using sulfhydryl-labeling strategies, we report the novel finding that all six cysteine (Cys) residues in the extracellular domain of SR-BI are involved in disulfide bond formation that is intramolecular by nature. We hypothesize that an SR-BI conformation stabilized by extracellular disulfide bonds is a prerequisite of SR-BI-mediated cholesterol transport. Thus, single Cys mutant SR-BI receptors (C251S-, C280S-, C321S-, C323S-, C334S- and C384S-SR-BI), as well as Cys-less-SR-BI, a mutant SR-BI receptor void of all Cys residues, were created and plasma membrane localization was confirmed. Functional assays revealed that C280S-, C321S-, C323S-, C334S- and Cys-less SR-BI mutant receptors displayed reduced HDL binding and subsequent selective uptake of HDL-CE. However, only C323S-SR-BI and Cys-less-SR-BI were unable to mediate wild-type levels of efflux of free cholesterol (FC) to HDL. None of the Cys mutations disrupted SR-BI’s ability to redistribute plasma membrane FC. Taken together, the intramolecular disulfide bonds in the extracellular domain of SR-BI appear to maintain the receptor in a conformation integral to its cholesterol transport functions.
The binding of high density lipoprotein (HDL) to scavenger receptor BI (SR-BI) is responsible for whole-body cholesterol disposal via reverse cholesterol transport. The extracellular domain of SR-BI is required for HDL binding and selective uptake of HDL-cholesterol. We identified six highly hydrophobic regions in this domain that may be important for receptor activity and performed sitedirected mutagenesis to investigate the importance of these regions in SR-BI-mediated cholesterol transport. Non-conservative mutation of the regions encompassing V67, L140/L142, V164 or V221 reduced hydrophobicity and impaired the ability of SR-BI to bind HDL, mediate selective uptake of HDL-cholesterol, promote cholesterol efflux, and enlarge the cholesterol oxidase-sensitive pool of membrane free cholesterol. In contrast, conservative mutations at V67, V164 or V221 did not affect the hydrophobicity or these cholesterol transport activities. We conclude that the hydrophobicity of N-terminal extracellular regions of SR-BI is critical for cholesterol transport, possibly by mediating receptor-ligand and/or receptor-membrane interactions.
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