Protective effect of melatonin on cigarette smoke‐induced restenosis in rat carotid arteries after balloon injury

Vascular restenosis after the interventional angioplasty remains the main obstacle to a favorable long‐term patency. Many researches suggest cigarette smoking is one of the most important causes of restenosis. This study was designed to investigate whether melatonin could protect against the cigarette smoke‐induced restenosis in rat carotid arteries after balloon injury. Three groups of male rats (normal condition, cigarette smoke exposed, cigarette smoke exposed, and melatonin injected) were used in this study. An established balloon‐induced carotid artery injury was performed, and the carotid arteries were harvested from these three groups 14 days later. The ratio of intima to media, the infiltration of inflammatory cells, the expression of inflammatory cytokines (NF‐κB, IL‐1β, IL‐6, TNF‐α, MCP‐1), adhesion molecules (ICAM‐1, VCAM‐1), and eNOS were measured. The results showed that cigarette smoke exposure aggravated the stenosis of the lumen, promoted the infiltration of inflammatory cells and induced the expression of the inflammatory cytokines and adhesion molecules after the balloon‐induced carotid artery injury. Moreover, cigarette smoke exposure can inhibit the expression of eNOS. Particularly, we surprised that melatonin could minimize this effect caused by cigarette smoke. These results suggested that melatonin could prevent the cigarette smoke‐induced restenosis in rat carotid arteries after balloon injury and the mechanism of its protective effect may be the inhibition of the inflammatory reaction. This also implies melatonin has the potential therapeutic applicability in prevention of restenosis after the vascular angioplasty in smokers.     

Automation of the in vitro micronucleus and chromosome aberration assay for the assessment of the genotoxicity of the particulate and gas–vapor phase of cigarette smoke

Abstract

Total particulate matter (TPM) and the gas–vapor phase (GVP) of mainstream smoke from the Reference Cigarette 3R4F were assayed in the cytokinesis-block in vitro micronucleus (MN) assay and the in vitro chromosome aberration (CA) assay, both using V79-4 Chinese hamster lung fibroblasts exposed for up to 24?h. The Metafer image analysis platform was adapted resulting in a fully automated evaluation system of the MN assay for the detection, identification and reporting of cells with micronuclei together with the determination of the cytokinesis-block proliferation index (CBPI) to quantify the treatment-related cytotoxicity. In the CA assay, the same platform was used to identify, map and retrieve metaphases for a subsequent CA evaluation by a trained evaluator. In both the assays, TPM and GVP provoked a significant genotoxic effect: up to 6-fold more micronucleated target cells than in the negative control and up to 10-fold increases in aberrant metaphases. Data variability was lower in the automated version of the MN assay than in the non-automated. It can be estimated that two test substances that differ in their genotoxicity by approximately 30% can statistically be distinguished in the automated MN and CA assays. Time savings, based on man hours, due to the automation were approximately 70% in the MN and 25% in the CA assays. The turn-around time of the evaluation phase could be shortened by 35 and 50%, respectively. Although only cigarette smoke-derived test material has been applied, the technical improvements should be of value for other test substances.     

Household Smoking and Childhood Asthma in the United States: A State-Level Analysis

Background. The reason for the substantial geographic variation in the prevalence of childhood asthma is not known. Objective. To investigate the association between exposure to cigarette smoking in the home and childhood asthma at the state-level, toward improving current understanding of geographic variation in childhood asthma rates. Methods. Data were drawn from the National Children's Health Survey (NCHS, 2003), a representative sample (n = 102, 000) of youth 0 to 17 years of age in the United States. Household smoking and asthma in children were reported by parents. Air quality for each state was obtained from Environmental Protection Act (EPA) reports, and state-level poverty reports were obtained from the US Department of Agriculture. Results. Household smoking was associated with a statistically significant increase in risk of asthma among children at the state level (p = 0.026). This association did not appear to be influenced by outdoor air quality at the state level or socioeconomic position. Conclusions. These results are the first to show a link between cigarette smoking in the home and childhood asthma at a state-level in the United States.     

Low-level environmental tobacco smoke exposure and inflammatory biomarkers in children with asthma

Objective: The effects of low-level environmental tobacco smoke (ETS) exposure, on asthma control, lung function and inflammatory biomarkers in children with asthma have not been well studied. The objective of the study was to assess ETS exposure in school-age children with asthma whose parents either deny smoking or only smoke outside the home, and to assess the impact of low-level ETS exposure on asthma control, spirometry and inflammatory biomarkers. Methods: Forty patients age 8–18 years with well-controlled, mild-to-moderate persistent asthma treated with either inhaled corticosteroids (ICS) or montelukast were enrolled. Subjects completed an age-appropriate Asthma Control Test and a smoke exposure questionnaire, and exhaled nitric oxide (FeNO), spirometry, urinary cotinine and leukotriene E₄ (LTE₄) were measured. ETS-exposed and unexposed groups were compared. Results: Only one parent reported smoking in the home, yet 28 (70%) subjects had urinary cotinine levels ≥1?ng/ml, suggesting ETS exposure. Seven subjects (18%) had FeNO levels >25parts per billion, six of whom were in the ETS-exposed group. In the ICS-treated subjects, but not in the montelukast-treated subjects, ETS exposure was associated with higher urinary LTE₄, p?=?0.04, but had no effect on asthma control, forced expiratory volume in 1?s or FeNO. Conclusions: A majority of school-age children with persistent asthma may be exposed to ETS, as measured by urinary cotinine, even if their parents insist they don’t smoke in the home. Urinary LTE₄ was higher in the ETS-exposed children treated with ICS, but not in children treated with montelukast.     

Trends in and predictors of second‐hand smoke exposure indexed by cotinine in children in England from 1996 to 2006

Aims To explore trends in and predictors of second‐hand smoke (SHS) exposure in children. To identify whether inequalities in SHS exposure are changing over time. Design Repeated cross‐sectional study with data from eight annual surveys conducted over an 11‐year period from 1996 to 2006. Setting England. Participants Nationally representative samples of children aged 4–15 years living in private households. Measurements Saliva cotinine (4–15‐year‐olds), current smoking status (8–15‐year‐olds), smoking status of parents and carers, smoking in the home, socio‐demographic variables. Findings The most important predictors of SHS exposure were modifiable factors—whether people smoke in the house on most days, whether the parents smoke and whether the children are looked after by carers who smoke. Children from more deprived households were more exposed and this remained the case even after parental smoking status has been controlled for. Exposure over time has fallen markedly among children (59% decline over 11 years in geometric mean cotinine), with the most marked decline observed in the period immediately preceding smoke‐free legislation. Declines in exposure have generally been greater in children most exposed at the outset. For example, in children whose parents both smoke, median cotinine declined annually by 0.115 ng/ml compared with 0.019 ng/ml where neither parent smokes (P < 0.05). Conclusions In the 11 years leading up to smoke‐free legislation in England, the overall level of SHS exposure in children as well as absolute inequalities in exposure have been declining. Further efforts to encourage parents and carers to quit and to avoid smoking in the home would benefit child health.     

How does the pitch and pattern of a signal affect auditory arousal thresholds?

How arousal thresholds vary with different sounds is a critical issue for emergency awakenings, especially as sleepers are dying in fires despite having a working smoke alarm. Previous research shows that the current high-pitched (3000+ Hz) smoke alarm signal is significantly less effective than an alternative signal, the 520 Hz square wave, in all populations tested. However, as the number of sounds tested has been small further research is needed. Here we measured auditory arousal thresholds (AATs) across signals with a range of characteristics to determine the most effective waking signal. Thirty-nine young adults participated over three nights. In Part A, nine signals were presented in stage 4 sleep with ascending decibel levels. Signals were short beeps in the low- to mid-frequency range with different spectral complexities: square waves, pure tones, whoops and white noise. Part B manipulated temporal patterns, inserting silences of 0, 10 and 21 s after each 12 s of beeps. It was found that the low-frequency (400 and 520 Hz) square waves yielded significantly lower AATs than the alternatives. A trend was found across the three temporal manipulations, with a 10 s intervening silence showing some advantage. These findings support earlier research indicating that the best sound for awakening from deep sleep is a low-frequency square wave. It is argued that the signal with the lowest response threshold when awake may be the same as the most arousing signal when asleep, especially where the sleeper processes the signal as meaningful.     

The effects of low-level environmental tobacco smoke exposure on pulmonary function tests in preschool children with asthma

Objectives: Though parents of children with asthma smoke, they often avoid smoking in their homes or near their children, thus limiting exposure. It is not known if such low-level environmental tobacco smoke (ETS) results in measurable exposure or affects lung function. The objectives of this study were to measure urinary cotinine in preschool children with asthma, and to examine the relationship between low-level ETS exposure and pulmonary function tests (PFTs). Methods: Preschool children with asthma were enrolled. Parents completed questionnaires on ETS exposure and asthma control, urinary cotinine concentrations were measured and PFTs were compared between subjects with and without recent ETS exposure. Results: Forty one subjects were enrolled. All parents denied smoking in their home within the last 2 weeks, but 14 (34%) parents admitted to smoking outside their homes or away from their children. Fifteen (37%; 95%CI: 23–53) of the children had urinary cotinine levels ≥1?ng/ml, of which seven (17%; 95%CI: 8–32) had levels ≥5?ng/ml. FEV₁ and FEV_0.5 were lower in subjects with a urinary cotinine level ≥5?ng/ml as compared to those with levels <1?ng/ml or between 1 and 5?ng/ml; both at baseline and after inhalation of albuterol. Five of seven subjects with urinary cotinine levels ≥5?ng/ml had FEV_0.5 less than 65% of predicted values. There were no significant differences in IOS measures. Conclusions: Despite parental denial of smoking near their children, preschool children may be exposed to ETS. Such low-level ETS exposure may affect lung function, possibly in a dose-dependent manner.     

Evidence for a possible anatomical subsite–mediated effect of tobacco in oral potentially malignant disorders and carcinoma

J Oral Pathol Med (2011) 40 : 214–217 Purpose: To test the hypothesis that cigarette smokers develop oral potentially malignant disorders or carcinomas in preferential anatomical subsites. Methods: The association of smoking habit with the presence of oral lesions in specific anatomical subsites was assessed in 123 patients using the odds ratio analysis. Results: When compared to all the other subsites, the relative frequency of smokers with lesions was higher in the buccal mucosa and in the floor of the mouth (FOM) (P = 0.002 and P = 0.005), while it was lower in the tongue (P < 0.0005). Smokers were about 7 years younger than non‐smokers (P = 0.008). Conclusions: The association of smoking and age suggests that smoking may contribute to generate a field of injury that leads to lesions in shorter periods than other causes. The stronger relationship of smoking with lesions in the buccal mucosa and FOM than in the tongue suggests that tissue characteristics mediate the effects of tobacco.