Urinary cotinine concentration in flight attendants, in relation to exposure to environmental tobacco smoke during intercontinental flights

Objectives: To measure and compare the urinary cotinine concentration (U-cotinine) in non-smoking cabin attendants (C/A) working with the Scandinavian Airlines System, before and after work on intercontinental flights with exposure to environmental tobacco smoke (ETS). Methods: The study material consisted of 24 cabin attendants and one pilot, all volunteers and all without exposure to ETS in the home, working on 15 intercontinental flights. Information on age, gender and occupation was gathered, as well as possible sources of ETS exposure in other places, outside work and during previous flights, during a 3-day period prior to the investigation. Urine samples were taken before departure and after landing, on board, and were kept frozen (−20 °C) until analysis. Cotinine was analyzed by a previously developed gas chromatographic method, using mass spectrometry (MS) with selected-ion monitoring (SIM). The difference in U-cotinine before and after the flight was compared. Moreover, the change in U-cotinine during the flight was related to occupation (work in the forward or aft galley) and observed degree of smoking during each flight. Results: The median U-cotinine was 3.71 μg/g crea; 2.4 μg/l (unadjusted) (interquartile range 2.08–8.67 μg/g crea) before departure, and 6.37 μg/g crea; 7.1 μg/l (interquartile range 3.98–19 μg/g crea) after landing, a significant difference (P < 0.003). C/A in the aft galley had a significantly higher concentration of U-cotinine after landing than subjects working in the front of the aircraft (P=0.01). In C/A working in the aft galley, the median increase of U-cotinine was 3.67 μg/g crea; 3.2 μg/l (interquartile range 0.04–13.8 μg/g crea) during flight. In contrast, those seven subjects working in the forward part of the aircraft had no increase in U-cotinine during the flight (median increase 0.97 μg/g crea; 0.5 μg/l interquartile range 0.27–2.65 μg/g crea). Conclusion: Tobacco smoking in commercial aircraft may cause significant exposure to environmental tobacco smoke among C/A working in the aft galley, despite high air exchange rates and spatial separation between smokers and non-smokers. This agrees with earlier studies, as well as measurements on the aircraft, showing a higher degree of ETS-related air pollution in the aft galley than in the forward galley. The average cotinine concentration in urine was similar to that in other groups with occupational exposure to ETS, e.g., restaurant staff, police interrogators and office workers. Since smoking in commercial aircraft may result in an involuntary exposure to ETS among non-smokers, it should be avoided. Received: 1 February 1999 / Accepted: 29 May 1999     

Plasma nicotine and cotinine levels following intravenous nicotine self-administration in rats

  Rationale: The route of nicotine administration between animal models and humans is very different and further investigation by determining levels of nicotine entering into the circulatory system is warranted. Objective: The present study addresses the validity of the rat self-administration procedure by comparing plasma levels of nicotine in the rat with levels reported in smokers following cigarette consumption. Methods: Plasma levels of nicotine and its metabolite cotinine were measured in 17 rats following intravenous self-administration of a range of nicotine doses (0.015, 0.03 and 0.06 mg/kg per infusion). Results: The two larger unit doses supported reliable self-administration behaviour with no overall difference in the patterns of nicotine intake. However, the total nicotine intake over the 2-h session was related to unit dose and this correlated highly with nicotine and cotinine levels measured in blood collected from the tail vein. On average, cotinine levels (50–200 ng/ml) were approximately 2-fold higher than nicotine levels (40–120 ng/ml) in plasma. Following an extinction test for one session in which saline was substituted for nicotine, no change in behaviour was observed in the two groups, while plasma levels of nicotine and cotinine dropped to nominal levels. Conclusions: The concentrations of nicotine attained following nicotine self-administration appear to be similar to levels reported in smokers after cigarette consumption, providing further validation of this procedure as an animal model of nicotine dependence. Received: 14 November 1998 / Final version: 4 January 1999     

Arterial/venous plasma nicotine concentrations following nicotine nasal spray

Background and objectives: Arterial (A) and venous (V) plasma nicotine and cotinine concentrations were measured after nasal nicotine spray in tobacco smokers of both genders. The hypothesis for this research was that a greater A/V difference in plasma nicotine would be present in males than females because males have greater skeletal muscle mass to bind nicotine. Subjects and methods: Nine male and nine female healthy adult smokers were studied. They all abstained from use of tobacco overnight for 10 h or more prior to the study. Nicotine nasal spray was given in doses of 1–2.5 mg total, with half in each nostril while the subject was supine. Both A and V blood samples were obtained prior to and 3, 6, 10, 15, 20, and 30 min post-nasal nicotine spray. Results and conclusions: Nasal nicotine administration produced greater A than V plasma levels. There were no gender differences in A/V nicotine concentrations, disproving the above hypothesis, suggesting that other physiochemical factors besides skeletal muscle mass must be involved. Heart rate increases correlated well with arterial plasma nicotine levels (r=0.77). Males had less variance than females in the expected increase in arterial plasma nicotine concentrations with increased number of nasal sprays. Although there was considerable overlap, mean A cotinine concentrations were consistently slightly larger than V concentrations. Received: 15 February 1999 / Accepted in revised form: 17 August 1999     

Cotinine concentrations in amniotic fluid and urine of smoking,passive smoking and non-smoking pregnant women at term and in the urine of their neonates on 1st day of life

Cotinine was measured in the amniotic fluid and urine of 31 pregnant women and in the urine of their offspring. Amniotic fluid cotinine was 8 times higher in active and 2.5 times higher in passive smokers than in non-smokers. In general, amniotic fluid cotinine was considerably higher than urinary cotinine both in active and in passive smokers. Estimation of cotinine both in amniotic fluid immediately before delivery and in urine of the newborn on the 1st day of life aids in assessing the degree of prenatal exposure to tobacco smoke.     

The influence of vitamin C on systemic markers of endothelial and inflammatory cell activation in smokers and non-smokers

Objective and design: To determine the influence of vitamin C supplementation (500 mg, bd, 14 days) on the circulating concentrations of soluble ICAM-1 (a marker of endothelial activation), neopterin (a marker of monocyte activation), and neutrophil elastase (a marker of neutrophil activation) in smokers and non-smokers in a randomised, double-blind, placebo-controlled trial in a hospital setting.Subjects: Twenty smokers (serum cotinine 20 ng ml^–1) and 20 age- and gender-matched non-smokers (serum cotinine 13.7 ng ml^–1).Results: At baseline, there was a significant elevation in the concentration of sICAM-1 in smokers (median 247, IQR 199 to 357 ng ml^–1) compared to non-smokers (median 207, IQR 189 to 227 ng ml^–1; p = 0.014). Vitamin C supplementation did not influence the circulating concentrations of ICAM-1 or neopterin, or leukocyte elastase activity, in smokers, non-smokers, or in the total population.Conclusions: Markers of monocyte and neutrophil activation were not influenced by smoking status in this study population. However, sICAM-1 concentrations were significantly elevated in tobacco smokers, reflecting tobacco-induced vascular activation that is unaffected by Vitamin C supplementation.Received 11 August 2004; returned for revision 8 November 2004; accepted by I. Ahnfelt-Rønne 21 November 2004     

Effects of cotinine on sperm motility, membrane function, and fertilizing capacity in vitro

We evaluated the effect of cotinine on sperm fertilizing capacity in vitro. Human spermatozoa were washed and re-suspended in medium containing albumin and various concentrations of cotinine (0, 100, 200, 400, or 800 ng/ml). After an 8-h incubation period, sperm motility, hypoosmotic swelling test (HOST) outcome, and the percentage of hyperactivated spermatozoa were assayed. Aliquots of spermatozoa were then processed for the zona-free hamster oocyte sperm penetration assay (SPA) or hamster ooplasmic injections. Spermatozoa exposed to concentrations of cotinine equal to 400 or 800 ng/ml demonstrated significantly smaller outcomes for all of the above with the exception of after hamster ooplasmic injections, where high cotinine concentrations did not affect sperm viability or sperm capacity to undergo decondensation and activate hamster oocytes. It appears that cotinine concentrations of 400 or 800 ng/ml exert a detrimental effect on sperm motility, membrane function, and the ability to undergo capacitation. In addition, the current findings suggest that smokers with a high seminal plasma cotinine concentration who participate in assisted reproduction programs may be treated with intracytoplasmic sperm injections (ICSI) rather than conventional in vitro fertilization (IVF) trials. Received: 25 November 1998 / Accepted: 24 September 1999     

Bone density and lifestyle characteristics in premenopausal and postmenopausal Chinese women

The relationships between bone health and various lifestyle factors were examined in a cross-sectional study in 775 Chinese women aged 35–75 years. Bone mass was significantly positively associated with body weight, height, body mass index (BMI) and duration of breastfeeding, but was not significantly associated with other lifestyle variables, including alcohol consumption, parity, age at menarche and age at menopause after adjusting for age and body weight. A positive association was observed in premenopausal women (but not in postmenopausal women) for bone density with current cigarette smoking and plasma and urinary cotinine (the major metabolite of smoking). However, the confounding effects of other unknown factors present in this cross-sectional study may not be excluded. Daily physical activity, as indicated by time spent working in the fields, was found consistently to be positively associated with bone mass (p<0.0001). When these women were grouped into three physical activity levels on the basis of occupation and daily work intensity, those undertaking heavy labor also had significantly higher radial bone mass than women undertaking light or medium labor. These results suggest a protective effect of daily physical activity on bone health in both pre- and postmenopausal women.     

毛细管气相色谱法测定头发中尼古丁及其代谢产物可的宁

目的建立毛细管气相色谱同时测定头发中尼古丁及其主要代谢产物可的宁的方法。方法头发样品经1.5mol/L NaOH溶液消解,二氯甲烷/甲醇(V/V,3∶1)溶剂萃取,氮气吹干,甲醇定容后直接进样。经SPB-5毛细管柱分离,火焰离子化检测器(FID)检测。结果在优化发样提取和色谱分析条件下,尼古丁和可的宁在4.3ng/mL~1mg/mL和10ng/mL~2mg/mL浓度范围内线性良好(r均为0.9996),方法检出限(S/N=3)分别为4.3ng/mL和10ng/mL。发样中尼古丁和可的宁的加标回收率分别为90.33%~113.1%和92.92%~117.4%,相对标准偏差为2.1%~7.0%和4.4%~8.9%。结论本方法灵敏度高,选择性好,操作简便、快速,易于推广,可用于控烟流行病调查研究批样的检测。     

Nicotine, but not cotinine, partially protects dopaminergic neurons against MPTP-induced degeneration in mice

In order to analyze the putative neuroprotective role of nicotine and cotinine in parkinsonian syndromes, these two compounds were administered in male C57Bl6 mice for 4 weeks. On day 8, four injections of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) were administered. MPTP intoxication induced a 50% loss of dopaminergic neurons in the substantia nigra and a 45% reduction in dopaminergic fibers in the striatum. Administration of cotinine did not affect MPTP toxicity in the nigrostriatal system but chronic nicotine treatment showed a slight protection (15%) of nigrostriatal dopaminergic neurons against MPTP.