Pharmacokinetic analysis of nicotine when using non-combustion inhaler type of tobacco product in Japanese adult male smokers

In a clinical study, the pharmacokinetics of nicotine were investigated using the prototype of a non-combustion inhaler type of tobacco product (PNCIT) with comparison to a 1 mg tar conventional cigarette (CC). The study was conducted in 12 healthy adult Japanese male smokers with an open-label non-randomized design to make an intra-subject comparison of the use or smoking of these products. Subjects used a single piece of PNCIT with 80 aspirations or smoked a CC with 10 puffs every hour, for a total of 12 PNCITs or CCs on each study day. Under this study regimen, the steady state plasma nicotine concentration was not significantly different between the test tobacco products. The time to reach the maximum plasma nicotine concentration was longer for PNCIT compared to CC, suggesting that nicotine delivered from PNCIT was absorbed primarily in the upper airway, not in the pulmonary sites as cigarette smoking. The relative bioavailability of nicotine for PNCIT compared to CC was 0.92 ± 0.32, indicating similar nicotine bioavailability for both forms. The difference in the elimination half-lives between the test products was not significant, suggesting that the elimination of nicotine from blood is not affected significantly by the difference in the nicotine absorption sites.     

同位素稀释超高效液相色谱-串联质谱法测定尿液中的可替宁

目的建立一种超高效液相色谱-串联质谱(UPLC-MS/MS)方法测定尿液中的可替宁,用于分析二手烟暴露儿童和成年吸烟者体内的尼古丁代谢情况。方法尿液样品加入可替宁d3同位素内标后用初始流动相稀释,涡旋混匀后过0.22μm滤膜进样分析。采用ACQUITY UPLC HSS T3色谱柱(2.1 mm×100 mm,1.8μm),流动相为0.01%甲酸的乙酸铵溶液(5 mmol/L)-乙腈,正离子扫描,多离子反应监测模式(MRM)检测,同位素内标法定量。结果方法的线性范围为0.1μg/L^150μg/L(r=0.9997),检出限为0.034μg/L(S/N=3)。样品加标回收率为97.0%~99.4%,相对标准偏差均<5.0%。利用该方法测定220份吸入二手烟的儿童和98份成年吸烟者尿液中可替宁的含量水平。结论本方法适用于尿液中可替宁的检测,具有操作简便、快速、灵敏、选择性好等特点。     

香烟烟雾暴露对雄性大鼠血浆尼古丁、可替宁的影响

目的 通过对吸烟大鼠血浆尼古丁、可替宁含量的测定,探讨香烟在体内的内暴露水平。方法 清洁级SD雄性大鼠160只,随机分为2、4、6、8、12周的低、中、高染毒剂量组及对照组,每组10只。采用呼吸道静式染毒,每日染毒一次,染毒周期为2、4、6、8、12周。观察大鼠的一般毒性效应,运用气相色谱-质谱联用法检测吸烟大鼠血浆中尼古丁、可替宁的含量。结果 香烟烟雾暴露组大鼠在第3周后逐渐开始出现间歇咳嗽,腹式呼吸加剧,鼻噪音等症状,暴露时间越长,症状越明显;染毒剂量越高,染毒周期越长,大鼠体重减少越明显,与空白对照组相比,差异有显著性（P < 0.01）;大鼠血浆尼古丁的保留时间为7.5~8.5 min,随暴露时间的延长,暴露剂量的增加,大鼠血浆中尼古丁含量较空白对照组（155±56.65）ng/mL有所增加;大鼠血浆可替宁的保留时间为11.5~12.5 min;随暴露时间的延长,暴露剂量的增加,大鼠血浆中可替宁含量较空白对照组（340±41.97）ng/mL有所增加,且呈现剂量-反应关系,不同暴露周期间可替宁含量的差异有显著性（P < 0.05）,且暴露时间与暴露剂量存在交互效应（P < 0.05）。结论 香烟烟雾暴露可造成大鼠机体不同程度的损伤,大鼠血浆可替宁浓度能够有效反映香烟烟雾内暴露情况,且呈现较好的剂量-反应关系。     

Root surface conditioning with nicotine or cotinine reduces viability and density of fibroblasts in vitro

The purpose of study was to evaluate fibroblast attachment and cellular morphology on root surfaces chemically conditioned with nicotine or cotinine. A secondary objective was to determine if mechanical scaling and root planning of these chemically conditioned surfaces would alter cellular attachment. Root surface dentin specimens were prepared from uniradicular teeth of non-smoking patients. Specimens were randomly assigned to two experimental groups: no treatment (chemical conditioning only) and scaling and root planning after conditioning (SRPC). The concentrations of the tested substances were in the range of 0–1 mg/mL (nicotine) and 0–1 ?g/mL (cotinine). After a 24-h conditioning period, dentin slices were incubated with continuous lineage of fibroblastic cells from rat (McCoy cells) for another 24 h. Specimens were prepared for SEM analysis and microphotographs. The statistical analysis of the data indicated significant alteration of cellular morphology on fibroblasts that were grown on root surface exposed to nicotine concentrations greater than 1 ?g/mL. This effect of nicotine was not reduced by SRPC. On the other hand, in the SRPC group cellular density was greater. For cotinine-conditioned specimens, the greater concentrations also led to alteration on morphology, and these alterations were observed in the SRPC group as well. Cotinine did not induce significant changes on cellular density. The results indicated that fibroblasts are negatively influenced by nicotine present on the dentin substrate and also that scaling may reduce these effects. Cotinine treatment on root surfaces may alter cell morphology and density but these effects were less severe than that promoted by nicotine, and were not affected by scaling.     

Paternal exposure to cigarette smoke condensate leads to reproductive sequelae and developmental abnormalities in the offspring of mice

Paternal smoking is associated with infertility, birth defects and childhood cancers. Our earlier studies using cigarette smoke condensate (CSC) demonstrated several deleterious changes in male germ cells. Here, we hypothesize that chronic paternal exposure to CSC causes molecular and phenotypic changes in the sire and the offspring, respectively. In this mouse study, CSC caused DNA damage and cytotoxicity in testes via accumulation of benzo(a)pyrene (B[a]P) and cotinine. Decreased expression of growth arrest and DNA damage inducible alpha (Gadd45a), aryl hydrocarbon receptor (Ahr), and cyclin-dependent kinase inhibitor 1A (P21) was seen in CSC exposed testes. Apoptotic germ cell death was detected by induction of Fas, FasL, and activated caspase-3. The CSC-exposed males displayed reduction in sperm motility and fertilizing ability and sired pups with reduced body weight and crown-rump length, and smaller litter size with higher numbers of resorption. This model of CSC exposure demonstrates testicular toxicity and developmental defects in the offspring.     

Association between exposure to environmental tobacco smoke (ETS) and breastfeeding behaviour

AIM: A cross-sectional study was conducted to investigate the association between breastfeeding behaviour and exposure to environmental tobacco smoke (ETS). METHOD: Questionnaires were collected from 552 women. Blood and urine specimens were taken from part of the population at the time of delivery. The study population was classified into two groups: those exposed to ETS and those unexposed, based on self-reports from the subjects involved in the study. Cotinine levels in the urine and blood specimens were analysed by HPLC-UV under strict quality control procedures. RESULTS: There was a significant negative association between the exposure to ETS at home or in the workplace and the prevalence of breastfeeding in each of the 6 months following delivery using multiple logistic regression adjusted for other covariates. The cotinine levels in the urine and blood were dose-dependent, but not significantly so. However, women with lower cotinine levels had a higher probability of breastfeeding than those with higher levels. CONCLUSION: Women who are exposed to ETS have a low likelihood of breastfeeding. It is necessary for the government to regulate ETS in public areas and confined spaces in order to reduce the levels of ETS that women are exposed to.     

Long‐term cardiovascular reprogramming by short‐term perinatal exposure to nicotine's main metabolite cotinine

Aim

Gather ‘proof‐of‐concept’ evidence of the adverse developmental potential of cotinine (a seemingly benign biomarker of recent nicotine/tobacco smoke exposure).

Methods

Pregnant C57 mice drank nicotine‐ or cotinine‐laced water for 6 wks from conception (N_PRE = 2% saccharin + 100 μg nicotine/mL; C_PRE = 2% saccharin + 10 μg cotinine/mL) or 3 wks after birth (C_POST = 2% saccharin + 30 μg cotinine/mL). Controls drank 2% saccharin (CTRL). At 17 ± 1 weeks (male pups; CTRL n = 6; C_POST n = 6; C_PRE n = 8; N_PRE n = 9), we assessed (i) cardiovascular control during sleep; (ii) arterial reactivity ex vivo; and (iii) expression of genes involved in arterial constriction/dilation.

Results

Blood cotinine levels recapitulated those of passive smoker mothers’ infants. Pups exposed to cotinine exhibited (i) mild bradycardia – hypotension at rest (p < 0.001); (ii) attenuated (C_PRE, p < 0.0001) or reverse (C_POST; p < 0.0001) BP stress reactivity; (iii) adrenergic hypocontractility (p < 0.0003), low protein kinase C (p < 0.001) and elevated adrenergic receptor mRNA (p < 0.05; all drug‐treated arteries); and (iv) endothelial dysfunction (N_PRE only).

Conclusion

Cotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion into cotinine. Low‐level exposure to this metabolite may pose unrecognised perinatal risks. Adults must avoid inadvertently exposing a foetus or infant to cotinine as well as nicotine.     

Tobacco smoke biomarkers and cancer risk among male smokers in the Shanghai Cohort Study

Metabolites of tobacco smoke constituents can be quantified in urine and other body fluids providing a realistic measure of carcinogen and toxicant dose in a smoker. Many previous studies have demonstrated that these metabolites – referred to as biomarkers in this paper – are related to tobacco smoke exposure. The studies reviewed here were designed to answer another question: are these substances also biomarkers of cancer risk? Using a prospective study design comparing biomarker levels in cancer cases and controls, all of whom were smokers, the results demonstrate that several of these biomarkers – total cotinine, total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), r-1-,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), and total N′-nitrosonornicotine (NNN) – are biomarkers of cancer risk. Therefore, these biomarkers have the potential to become part of a cancer risk prediction algorithm for smokers.     

Auricular acupressure combined with multimedia instruction or alone for quitting smoking in young adults: A quasi-experimental study

Background

Smoking plays a disease-related risk factor and is however the principal cause of preventable death. Many studies support the use of combined rather than single interventions to stop smoking.

Objective

This study aimed to evaluate the effects of auricular acupressure combined with multimedia instruction in comparison with auricular acupressure alone on smoking cessation in young adults.

Method

A quasi-experimental research design was used and participants were assigned to experimental groups according to their preference. Group 1 received the 10-week program with auricular acupressure plus multimedia instruction; Group 2 received auricular acupressure alone. Thirty-two participants were in each group were recruited from universities in Taiwan. The physical and psychological data were collected right before and after the program.

Results

This study demonstrated the effects of smoking cessation on physical and psychological factors in each group. Statistical between-group differences existed in psychological factors of smoking cessation self-efficacy and nicotine dependence, but not in physical factors of carbon monoxide and cotinine.

Conclusions

This study adds to the body of research on the benefits of using auricular acupressure combined with or without multimedia instruction for smoking cessation in adolescents. The combined intervention was more effective especially in increasing smoking cessation self-efficacy and decreasing nicotine dependence. Further study is suggested adding control groups such as placebo in order to understand a single effect of smoking cessation.