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Sample records for acute cigarette smoke-induced

  1. The therapeutic effects of tuberostemonine against cigarette smoke-induced acute lung inflammation in mice.

    PubMed

    Jung, Kyung-Hwa; Beak, Hyunjung; Park, Soojin; Shin, Dasom; Jung, Jaehoon; Park, Sangwon; Kim, Jinju; Bae, Hyunsu

    2016-03-05

    Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking and is characterized by the destruction of lung parenchyma, structural alterations of the small airways, and systemic inflammation. Tuberostemonine (TS) is an alkaloid-type phytochemical from Stemona tuberosa. In the present study, we evaluated the anti-inflammatory effect of TS in a cigarette smoke (CS)-induced mouse model of acute lung inflammation. The mice were whole-body exposed to CS or fresh air for 7 days. TS was administered by an intraperitoneal (i.p.) injection 1h before exposure to CS. To test the effects of TS, the numbers of total cells, neutrophils, macrophages and lymphocytes in the bronchoalveolar lavage (BAL) fluid were counted. Furthermore, we measured the levels of several chemokines, such as GCP-2, MIP-3α, MCP-1 and KC, in the lung tissue. The cellular profiles and histopathological analysis demonstrated that the infiltration of peribronchial and perivascular inflammatory cells significantly decreased in the TS-treated groups compared with the CS-exposure group. The TS treatment significantly ameliorated the airway epithelial thickness induced by CS exposure and caused a significant decrement in the production of chemokines in the lung. These results suggest that TS has anti-inflammatory effects against CS-induced acute lung inflammation.

  2. Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway.

    PubMed

    Ge, Ling-tian; Liu, Ya-nan; Lin, Xi-xi; Shen, Hui-juan; Jia, Yong-liang; Dong, Xin-wei; Sun, Yun; Xie, Qiang-min

    2016-04-01

    Oral and injection administration of ambroxol has been clinically used to treat airway disease. However, little is known about its potentials in inhalation therapy. In present studies, we tested the effects of ambroxol by inhalation with intravenous administration, and explored the underlying working mechanism. The mice received 10 cigarettes exposure every day for 4 days. Inhaled solution of ambroxol was aerosolized 20 min before the exposure of cigarette smoke (CS). The effect of ambroxol on the expression of mucoprotein 5 AC (MUC5AC) and proinflammatory cytokines in NCI-H292 cells stimulated with cigarette smoke extract (CSE). Four days of daily inhalation of ambroxol at 3.75 or 7.5mg/ml for 20 min suppressed the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited increases in the mRNA and protein levels of tumor necrosis factor (TNF)-α, CCL-2 and KC, but not interleukin (IL)-1β in the CS-exposed mice. Moreover, ambroxol at 3.75 or 7.5mg/ml facilitated airway mucosa cilia clearance, reduced glycosaminoglycans level in BALF and MUC5AC mRNA levels in lung tissues. The effects of ambroxol by inhalation at 7.5mg/ml was comparable to that of ambroxol at 20mg/kg i.v. and dexamethasone at 0.5mg/kg i.p. Using cultured lung epithelial cells, we demonstrated that pretreatment with ambroxol at 2 or 20 μM inhibited the CSE-induced up-regulation of MUC5AC, TNF-α, IL-1β mRNA levels, which was through inhibiting Erk signaling pathway. Our results demonstrate the beneficial effects of ambroxol as an inhalation replace systemic administration for COPD therapy.

  3. Bacoside A: Role in Cigarette Smoking Induced Changes in Brain

    PubMed Central

    Vani, G.; Anbarasi, K.; Shyamaladevi, C. S.

    2015-01-01

    Cigarette smoking (CS) is a major health hazard that exerts diverse physiologic and biochemical effects mediated by the components present and generated during smoking. Recent experimental studies have shown predisposition to several biological consequences from both active and passive cigarette smoke exposure. In particular, passive smoking is linked to a number of adverse health effects which are equally harmful as active smoking. A pragmatic approach should be considered for designing a pharmacological intervention to combat the adverse effects of passive smoking. This review describes the results from a controlled experimental condition, testing the effect of bacoside A (BA) on the causal role of passive/secondhand smoke exposure that caused pathological and neurological changes in rat brain. Chronic exposure to cigarette smoke induced significant changes in rat brain histologically and at the neurotransmitter level, lipid peroxidation states, mitochondrial functions, membrane alterations, and apoptotic damage in rat brain. Bacoside A is a neuroactive agent isolated from Bacopa monnieri. As a neuroactive agent, BA was effective in combating these changes. Future research should examine the effects of BA at molecular level and assess its functional effects on neurobiological and behavioral processes associated with passive smoke. PMID:26413118

  4. Betulin inhibited cigarette smoke-induced COPD in mice.

    PubMed

    Chunhua, Ma; Long, Hongyan; Zhu, Weina; Liu, Zheng; Jie, Ruan; Zhang, Yajie; Wang, Yarui

    2017-01-01

    The purpose of the present study was to evaluate the protective effect of betulin (BE) on CS (cigarette smoke)-induced COPD in mice and explore its underlying mechanisms. 60 male ICR mice were randomly assigned to five groups: control group, model group, dexamethasone (2mg/kg) group, BE (20mg/kg) group and BE (40mg/kg) group. The COPD mice were induced by cigarette smoke exposure for 8 weeks. The result of H&E staining demonstrated that BE inhibited CS-induced pathological injury in lung tissue. Besides, BE could restore the activities of superoxide dismutase (SOD) in serum and in lung, catalase (CAT) in serum and reduce the content of malondialdehyde (MDA) in serum and in lung. BE also inhibited the overproductions of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Furthermore, the administration of BE significantly inhibited the protein expression of ROCK/NF-κB pathway in CS-induced mice. Our findings suggested that BE might effectively ameliorate the progression of COPD via ROCK/NF-κB pathway in mice.

  5. Casticin, an active compound isolated from Vitex Fructus, ameliorates the cigarette smoke-induced acute lung inflammatory response in a murine model.

    PubMed

    Lee, Hyeonhoon; Jung, Kyung-Hwa; Lee, Hangyul; Park, Soojin; Choi, Woosung; Bae, Hyunsu

    2015-10-01

    The aim of this study was to determine of the effect of casticin, as an anti-inflammatory agent, on an acute lung inflammation in vivo model established through exposure to cigarette smoke (CS). Casticin is a phytochemical from Vitex species such as Vitex rotundifolia and Vitex agnus-castus that was recently shown to exert an anti-inflammatory effect in vivo. To demonstrate the effects of casticin, C57BL/6 mice were whole-body exposed to mainstream CS or fresh air for two weeks and treated with 1, 2, and 10mg/kg casticin via an i.p. injection. Immune cell infiltrations and cytokine productions were assessed from bronchoalveolar lavage Fluid (BALF), and lung histological analysis was performed. Treatment with casticin was observed to significantly inhibit the numbers of total cells, neutrophils, macrophages, and lymphocytes and reduce the levels of proinflammatory cytokines and chemokines in the BALF. In addition, casticin significantly decreased the infiltration of peribronchial and perivascular inflammatory cells and the epithelium thickness. The results of this study indicate that casticin has significant effects on the lung inflammation induced by CS in a mouse model. According to these outcomes, casticin may have therapeutic potential in inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD).

  6. Mecamylamine pretreatment counteracts cigarette smoke induced changes in hypothalamic catecholamine neuron systems and in anterior pituitary function.

    PubMed

    Andersson, K

    1985-11-01

    We have studied the effects of acute, intermittent exposure to tobacco smoke on discrete hypothalamic CA nerve terminal networks and on neuroendocrine function by means of quantitative histofluorimetrical determinations of catecholamine (CA) fluorescence in sections of rat brain and by radioimmunoassay procedures for hormones. Acute intermittent exposure to cigarette smoke induced a lowering of NA levels and increased NA turnover in discrete hypothalamic nerve terminal regions. This exposure also induced increases in DA turnover in the median eminence. The cigarette smoke lowered TSH, prolactin, LH and FSH serum levels, but induced an increase in serum corticosterone concentrations. To determine if the above mentioned changes in neuroendocrine function were nicotine mediated, a cholinergic nicotine-like blocking agent, mecamylamine, was administered prior to exposure to cigarette smoke. Pretreatment with mecamylamine (1.0 mg kg-1) counteracted the cigarette smoke induced changes in CA levels and turnover in all hypothalamic CA nerve terminal regions as well as the changes in serum levels of the pituitary hormones and corticosterone. It is suggested that acute intermittent exposure to cigarette smoke, via its nicotine component, lowers TSH, prolactin, LH and FSH secretion at least in part through activation of the tubero-infundibular DA neurons. Furthermore, the nicotine component of the cigarette smoke is suggested to induce the increase in corticosterone serum levels via increasing NA turnover in the paraventricular hypothalamic nucleus.

  7. Cigarette smoke induces methylation of the tumor suppressor gene NISCH

    PubMed Central

    Ostrow, Kimberly Laskie; Michalidi, Christina; Guerrero-Preston, Rafael; Hoque, Mohammad O.; Greenberg, Alissa; Rom, William; Sidransky, David

    2013-01-01

    We have previously identified a putative tumor suppressor gene, NISCH, whose promoter is methylated in lung tumor tissue as well as in plasma obtained from lung cancer patients. NISCH was observed to be more frequently methylated in smoker lung cancer patients than in non-smoker lung cancer patients. Here, we investigated the effect of tobacco smoke exposure on methylation of the NISCH gene. We tested methylation of NISCH after oral keratinocytes were exposed to mainstream and side stream cigarette smoke extract in culture. Methylation of the promoter region of the NISCH gene was also evaluated in plasma obtained from lifetime non-smokers and light smokers (< 20 pack/year), with and without lung tumors, and heavy smokers (20+ pack/year) without disease. Promoter methylation of NISCH was tested by quantitative fluorogenic real-time PCR in all samples. Promoter methylation of NISCH occurred after exposure to mainstream tobacco smoke as well as to side stream tobacco smoke in normal oral keratinocyte cell lines. NISCH methylation was also detected in 68% of high-risk, heavy smokers without detectable tumors. Interestingly, in light smokers, NISCH methylation was present in 69% of patients with lung cancer and absent in those without disease. Our pilot study indicates that tobacco smoke induces methylation changes in the NISCH gene promoter before any detectable cancer. Methylation of the NISCH gene was also found in lung cancer patients’ plasma samples. After confirming these findings in longitudinally collected plasma samples from high-risk populations (such as heavy smokers), examining patients for hypermethylation of the NISCH gene may aid in identifying those who should undergo additional screening for lung cancer. PMID:23503203

  8. Cellular mechanisms of mainstream cigarette smoke-induced lung epithelial tight junction permeability changes in vitro.

    PubMed

    Olivera, Dorian S; Boggs, Susan E; Beenhouwer, Chris; Aden, James; Knall, Cindy

    2007-01-01

    Mainstream cigarette smoke increases the permeability of human airways; however, the mechanism for this increased permeability is poorly defined. Tight junctions between adjacent epithelial cells constitute the physiological barrier to fluid and macromolecules in epithelium. These structures are highly regulated by phosphorylation and their association with the cytoskeleton. The goal of these studies was to identify the signal transduction pathways that regulate smoke-induced permeability. Using a physiologically relevant air-liquid interface exposure system, electrically tight monolayers of the human bronchial epithelial cell-line Calu-3 were exposed to fresh, whole mainstream cigarette smoke. This exposure results in a regulated, dose-dependent loss of epithelial barrier function in the lung epithelial monolayers. With cigarette smoke exposure, transepithelial electrical resistance (TER) is decreased and albumin flux is increased, indicating a loss in barrier function to ions and macromolecules, respectively; however, both largely recover in 30 min. Smoke-induced losses of macromolecular barrier function are the result of multicellular junctional reorganization, resulting in increased leak volume rather than leak frequency. Inhibiting Rho kinase (ROCK) significantly reduces the smoke-induced permeability to both ions and macromolecules, while inhibiting protein tyrosine kinases (PTK) only reduces smoke-induced macromolecular permeability. Interestingly, inhibiting myosin light chain kinase (MLCK) exacerbates smoke-induced permeability, indicating that MLCK and ROCK have opposing regulatory roles. Our results demonstrate that the smoke-induced loss of epithelial barrier function in human bronchial epithelium is a regulated process rather than a cytotoxic response. Additionally, our results indicate that activation of PTK and ROCK and inactivation of MLCK contribute to the increased airway permeability caused by mainstream cigarette smoke.

  9. A new experimental model of cigarette smoke-induced emphysema in Wistar rats*, **

    PubMed Central

    Kozma, Rodrigo de las Heras; Alves, Edson Marcelino; Barbosa-de-Oliveira, Valter Abraão; Lopes, Fernanda Degobbi Tenorio Quirino dos Santos; Guardia, Renan Cenize; Buzo, Henrique Vivi; de Faria, Carolina Arruda; Yamashita, Camila; Cavazzana, Manzelio; Frei, Fernando; Ribeiro-Paes, Maria José de Oliveira; Ribeiro-Paes, João Tadeu

    2014-01-01

    OBJECTIVE: To describe a new murine model of cigarette smoke-induced emphysema. METHODS: Twenty-four male Wistar rats were divided into two groups: the cigarette smoke group, comprising 12 rats exposed to smoke from 12 commercial filter cigarettes three times a day (a total of 36 cigarettes per day) every day for 30 weeks; and the control group, comprising 12 rats exposed to room air three times a day every day for 30 weeks. Lung function was assessed by mechanical ventilation, and emphysema was morphometrically assessed by measurement of the mean linear intercept (Lm). RESULTS: The mean weight gain was significantly (approximately ten times) lower in the cigarette smoke group than in the control group. The Lm was 25.0% higher in the cigarette smoke group. There was a trend toward worsening of lung function parameters in the cigarette smoke group. CONCLUSIONS: The new murine model of cigarette smoke-induced emphysema and the methodology employed in the present study are effective and reproducible, representing a promising and economically viable option for use in studies investigating the pathophysiology of and therapeutic approaches to COPD. PMID:24626269

  10. Role of activin-A in cigarette smoke-induced inflammation and COPD.

    PubMed

    Verhamme, Fien M; Bracke, Ken R; Amatngalim, Gimano D; Verleden, Geert M; Van Pottelberge, Geert R; Hiemstra, Pieter S; Joos, Guy F; Brusselle, Guy G

    2014-04-01

    Activin-A is a pleiotropic cytokine belonging to the transforming growth factor-β superfamily and has been implicated in asthma and pulmonary fibrosis. However, the role of activin-A and its endogenous inhibitor, follistatin, in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown. We first quantified activin-A and follistatin in the lungs of air- or cigarette smoke-exposed mice and in the lungs of patients with COPD by immunohistochemistry, ELISA and quantitative real-time PCR. We subsequently studied the effect of cigarette smoke on primary human bronchial epithelial cells in vitro. Next, activin-A signalling was antagonised in vivo by administration of follistatin in mice exposed to air or cigarette smoke for 4 weeks. Protein levels of activin-A were increased in the airway epithelium of patients with COPD compared with never-smokers and smokers. Cigarette smoke-exposed human bronchial epithelial cells expressed higher levels of activin-A and lower levels of follistatin. Both mRNA and protein levels of activin-A were increased in the lungs of cigarette smoke-exposed mice, whereas follistatin levels were reduced upon cigarette smoke exposure. Importantly, administration of follistatin attenuated the cigarette smoke-induced increase of inflammatory cells and mediators in the bronchoalveolar lavage fluid in mice. These results suggest that an imbalance between activin-A and follistatin contributes to the pathogenesis of cigarette smoke-induced inflammation and COPD.

  11. Ceramides mediate cigarette smoke-induced metabolic disruption in mice.

    PubMed

    Thatcher, Mikayla O; Tippetts, Trevor S; Nelson, Michael B; Swensen, Adam C; Winden, Duane R; Hansen, Melissa E; Anderson, Madeline C; Johnson, Ian E; Porter, James P; Reynolds, Paul R; Bikman, Benjamin T

    2014-11-15

    Cigarette smoke exposure increases lung ceramide biosynthesis and alters metabolic function. We hypothesized that ceramides are released from the lung during cigarette smoke exposure and result in elevated skeletal muscle ceramide levels, resulting in insulin resistance and altered mitochondrial respiration. Employing cell and animal models, we explored the effect of cigarette smoke on muscle cell insulin signaling and mitochondrial respiration. Muscle cells were treated with conditioned medium from cigarette smoke extract (CSE)-exposed lung cells, followed by analysis of ceramides and assessment of insulin signaling and mitochondrial function. Mice were exposed to daily cigarette smoke and a high-fat, high-sugar (HFHS) diet with myriocin injections to inhibit ceramide synthesis. Comparisons were conducted between these mice and control animals on standard diets in the absence of smoke exposure and myriocin injections. Muscle cells treated with CSE-exposed conditioned medium were completely unresponsive to insulin stimulation, and mitochondrial respiration was severely blunted. These effects were mitigated when lung cells were treated with the ceramide inhibitor myriocin prior to and during CSE exposure. In mice, daily cigarette smoke exposure and HFHS diet resulted in insulin resistance, which correlated with elevated ceramides. Although myriocin injection was protective against insulin resistance with either smoke or HFHS, it was insufficient to prevent insulin resistance with combined CS and HFHS. However, myriocin injection restored muscle mitochondrial respiration in all treatments. Ceramide inhibition prevents metabolic disruption in muscle cells with smoke exposure and may explain whole body insulin resistance and mitochondrial dysfunction in vivo.

  12. Bone marrow cells repair cigarette smoke-induced emphysema in rats.

    PubMed

    Huh, Jin Won; Kim, Sun-Yong; Lee, Ji Hyun; Lee, Jin-Seok; Van Ta, Quang; Kim, Mijung; Oh, Yeon-Mok; Lee, Yun-Song; Lee, Sang-Do

    2011-09-01

    The therapeutic potential of stem cells in chronic obstructive pulmonary disease is not well known although stem cell therapy is effective in models of other pulmonary diseases. We tested the capacities of bone marrow cells (BMCs), mesenchymal stem cells (MSCs), and conditioned media of MSCs (MSC-CM) to repair cigarette smoke-induced emphysema. Inbred female Lewis rats were exposed to cigarette smoke for 6 mo and then received BMCs, MSCs, or MSC-CM from male Lewis rats. For 2 mo after injection, the BMC treatment gradually alleviated the cigarette smoke-induced emphysema and restored the increased mean linear intercept. The BMC treatment significantly increased cell proliferation and the number of small pulmonary vessels, reduced apoptotic cell death, attenuated the mean pulmonary arterial pressure, and inhibited muscularization in small pulmonary vessels. However, only a few male donor cells were detected from 1 day to 1 mo after BMC administration. The MSCs and cell-free MSC-CM also induced the repair of emphysema and increased the number of small pulmonary vessels. Our data show that BMC, MSCs, and MSC-CM treatment repaired cigarette smoke-induced emphysema. The repair activity of these treatments is consistent with a paracrine effect rather than stem cell engraftment because most of the donor cells disappeared and because cell-free MSC-CM also induced the repair.

  13. p38 mitogen-activated protein kinase mediates sidestream cigarette smoke-induced endothelial permeability.

    PubMed

    Low, Brad; Liang, Mei; Fu, Jian

    2007-07-01

    Second-hand smoke is associated with increased risk of cardiovascular diseases. So far, little is known about the signaling mechanisms of second-hand smoke-induced vascular dysfunction. Endothelial junctions are fundamental structures important for maintaining endothelial barrier function. Our study showed that sidestream cigarette smoke (SCS), a major component of second-hand smoke, was able to disrupt endothelial junctions and increase endothelial permeability. Sidestream cigarette smoke stimulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and myosin light chain (MLC). A selective inhibitor of p38 MAPK (SB203580) prevented SCS-induced loss of endothelial barrier integrity as evidenced by transendothelial resistance measurements. Resveratrol, an antioxidant that was able to inhibit SCS-induced p38 MAPK and MLC phosphorylation, also protected endothelial cells from the damage. Thus, p38 MAPK mediates SCS-induced endothelial permeability. Inhibition of p38 MAPK may have therapeutic potential for second-hand smoke-induced vascular injury.

  14. Animal models of cigarette smoke-induced chronic obstructive pulmonary disease.

    PubMed

    Wright, Joanne L; Churg, Andrew

    2010-12-01

    Chronic exposure of laboratory animals to cigarette smoke reproduces many of the anatomic/physiologic lesions (emphysema, small-airway remodeling and pulmonary hypertension) of human chronic obstructive pulmonary disease, although smoke-exposed laboratory animals are not good models of chronic bronchitis or acute exacerbations, as these are conditions based upon symptoms that are not recapitulated in animals. Many types of antiproteolytic and anti-inflammatory interventions, such as use of drugs or genetic modifications, are highly effective in preventing emphysema in these models, and some also prevent small-airway remodeling and pulmonary hypertension. However, the few attempts to translate these therapies into humans have been unsuccessful, probably because the animal models typically start therapy from day 1 of smoke exposure, whereas most humans are treated late in the course of their disease. Recent data from our laboratory suggest that the parenchyma can repair smoke-induced damage for some period, but then switches to a mode where it fails to repair; these observations suggest that the timing of an intervention in humans may be crucial to its success. The various different anatomic lesions induced by smoke appear to be largely independent effects and may require different therapeutic approaches.

  15. p38 mitogen-activated protein kinase determines the susceptibility to cigarette smoke-induced emphysema in mice

    PubMed Central

    2014-01-01

    Background There is a need for agents that suppress inflammation and progression of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase (p38 MAPK) has been associated with this disorder, and several inhibitors of this cascade are in clinical trials for its treatment, but their efficacy and utility are unknown. This study evaluated the relationship between p38 MAPK activation and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its inhibition ameliorated the lung inflammation and injury in murine models of cigarette smoke exposure. Methods In acute and chronic CS exposure, the activation and expression of p38 MAPK in the lungs, as well as lung inflammation and injury (proteinase production, apoptosis, and oxidative DNA damage), were compared between two mouse strains: C57BL/6 (emphysema-susceptible) and NZW (emphysema-resistant). The selective p38 MAPK inhibitor SB203580 (45 mg/kg) was administrated intra-peritoneally to C57BL/6 mice, to examine whether it ameliorated cigarette smoke-induced lung inflammation and injury. Results Acute CS-induced lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2), proteinase expression (MMP-12 mRNA), apoptosis, and oxidative DNA damage were significantly lower in NZW than C57BL/6 mice. p38 MAPK was significantly activated and up-regulated by both acute and chronic CS exposure in C57BL/6 but not NZW mice. mRNA expression of p38 MAPK was also upregulated in C57BL/6 by chronic CS exposure and tended to be constitutively suppressed in NZW mice. SB203580 significantly attenuated lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2, protein levels of KC, MIP-1α, IL-1β, and IL-6), proteinase expression (MMP-12 mRNA), oxidative DNA damage, and apoptosis caused by acute CS exposure. Conclusions Cigarette smoke activated p38 MAPK only in mice that were susceptible to cigarette smoke-induced emphysema. Its selective inhibition ameliorated

  16. Cigarette sidestream smoke induces phosphorylated histone H2AX.

    PubMed

    Toyooka, Tatsushi; Ibuki, Yuko

    2009-05-31

    Cigarette sidestream smoke (CSS) is a widespread environmental pollutant having highly genotoxic potency. In spite of the overwhelming evidence that CSS induces a wide range of DNA damage such as oxidative base damage and DNA adducts, evidence that CSS can result in DNA double strand breaks (DSBs) is little. In this study, we showed that CSS generated phosphorylated histone H2AX (gamma-H2AX), recently considered as a sensitive marker of the generation of DSBs, in a human pulmonary epithelial cell model, A549. Treatment with CSS drastically induced discrete foci of gamma-H2AX within the nucleus in a dose-dependent manner. CSS increased intracellular oxidation, and N-acetylcysteine (NAC), an antioxidant, significantly attenuated the formation of gamma-H2AX, suggesting that reactive oxygen species produced from CSS partially contributed to the phosphorylation. The generation of gamma-H2AX is considered to be accompanied the induction of DSBs. CSS in fact induced DSBs, which was also inhibited by NAC. DSBs are the worst type of DNA damage, related to genomic instability and carcinogenesis. Our results would increase the evidence of the strong genotoxicity of passive smoking.

  17. Vitamin C prevents cigarette smoke-induced pulmonary emphysema in mice and provides pulmonary restoration.

    PubMed

    Koike, Kengo; Ishigami, Akihito; Sato, Yasunori; Hirai, Toyohiro; Yuan, Yiming; Kobayashi, Etsuko; Tobino, Kazunori; Sato, Tadashi; Sekiya, Mitsuaki; Takahashi, Kazuhisa; Fukuchi, Yoshinosuke; Maruyama, Naoki; Seyama, Kuniaki

    2014-02-01

    Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.

  18. Could charcoal filtration of cigarette smoke reduce smoking-induced disease? A review of the literature.

    PubMed

    Coggins, Christopher R E; Gaworski, Charles L

    2008-04-01

    A review of the published work with charcoal-filtered cigarettes indicates that there are reductions in the concentrations for many gas-vapor phase constituents found in mainstream smoke. However, charcoal filters provided no apparent capacity for reduction of smoke particulate phase components. The reductions in gas-vapor phase smoke chemistry analytes generally correspond with findings of reduced toxicological activity, principally related to a reduction in the cytotoxic action of the volatile smoke constituents. Results of a short-term clinical study show small reductions in the biomarkers of the gas-vapor phase smoke constituents in subjects smoking charcoal-filtered cigarettes, compared to subjects smoking non-charcoal filtered cigarettes. The very limited epidemiology data (a single study) fail to demonstrate a conclusive beneficial effect of charcoal-filtered cigarette products compared to non-charcoal filtered cigarette products. Review of the scientific literature is hindered due to the lack of documentation regarding the activity of the charcoal used in the filter, and the inconsistency in product designs used between the various different disciplines (chemistry, pre-clinical, clinical and epidemiology) that have conducted studies with charcoal filtered cigarettes. There do not appear to be any published studies using a combination of data from the different disciplines based on a consistently designed charcoal cigarette filter. Although the literature presently available would suggest that smoke filtration provided by current charcoal filter techniques alone may not be substantial enough to reduce smoking-related disease, the data are limited. Therefore, for the reduction of smoking-induced disease, it is difficult to come to a definitive conclusion regarding the potential health benefits of using charcoal as a smoke filtration technology.

  19. Brain-derived neurotrophic factor in cigarette smoke-induced airway hyperreactivity.

    PubMed

    Sathish, Venkatachalem; Vanoosten, Sarah Kay; Miller, Brent S; Aravamudan, Bharathi; Thompson, Michael A; Pabelick, Christina M; Vassallo, Robert; Prakash, Y S

    2013-04-01

    Enhanced airway smooth muscle (ASM) contractility contributes to increased resistance to airflow in diseases such as bronchitis and asthma that occur in passive smokers exposed to secondhand smoke. Little information exists on the cellular mechanisms underlying such airway hyperreactivity. Sputum samples of patients with chronic sinusitis, bronchitis, and asthma show increased concentrations of growth factors called neurotrophins, including brain-derived growth factor (BDNF), but their physiological significance remains unknown. In human ASM, we tested the hypothesis that BDNF contributes to increased contractility with cigarette smoke exposure. The exposure of ASM to 1% or 2% cigarette smoke extract (CSE) for 24 hours increased intracellular calcium ([Ca(2+)](i)) responses to histamine, and further potentiated the enhancing effects of a range of BDNF concentrations on such histamine responses. CSE exposure increased the expression of the both high-affinity and low-affinity neurotrophin receptors tropomyosin-related kinase (Trk)-B and p75 pan-neurotrophin receptor, respectively. Quantitative ELISA showed that CSE increased BDNF secretion by human ASM cells. BDNF small interfering (si)RNA and/or the chelation of extracellular BDNF, using TrkB-fragment crystallizable, blunted the effects of CSE on [Ca(2+)](i) responses as well as the CSE enhancement of cell proliferation, whereas TrkB siRNA blunted the effects of CSE on ASM contractility. These data suggest that cigarette smoke is a potent inducer of BDNF and TrkB expression and signaling in ASM, which then contribute to cigarette smoke-induced airway hyperresponsiveness.

  20. Damage to Olfactory Progenitor Cells Is Involved in Cigarette Smoke-Induced Olfactory Dysfunction in Mice.

    PubMed

    Ueha, Rumi; Ueha, Satoshi; Kondo, Kenji; Sakamoto, Takashi; Kikuta, Shu; Kanaya, Kaori; Nishijima, Hironobu; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-03-01

    Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms by which cigarette smoke interferes with the highly regenerative olfactory nerve system remain unclear. To investigate whether cigarette smoke induces olfactory dysfunction by disrupting cell proliferation and cell survival in the olfactory epithelium (OE), we developed a mouse model of smoking that involved intranasal administration of a cigarette smoke solution (CSS). Immunohistological analyses and behavioral testing showed that CSS administration during a period of 24 days reduced the number of olfactory marker protein-positive mature olfactory receptor neurons (ORNs) in the OE and induced olfactory dysfunction. These changes coincided with a reduction in the number of SOX2(+) ORN progenitors and Ki-67(+) proliferating cells in the basal layer of the OE, an increase in the number of caspase-3(+) apoptotic cells, and an increase in the expression of mRNA for the inflammatory cytokines IL-1β and IL-6. Notably, the proliferating ORN progenitor population recovered after cessation of treatment with CSS, resulting in the subsequent restoration of mature ORN numbers and olfaction. These results suggest that SOX2(+) ORN progenitors are targets of CSS-induced impairment of the OE, and that by damaging the ORN progenitor population and increasing ORN death, CSS exposure eventually overwhelms the regenerative capacity of the epithelium, resulting in reduced numbers of mature ORNs and olfactory dysfunction.

  1. Src mediates cigarette smoke-induced resistance to tyrosine kinase inhibitors in NSCLC cells.

    PubMed

    Filosto, Simone; Baston, David S; Chung, Samuel; Becker, Cathleen R; Goldkorn, Tzipora

    2013-08-01

    The EGF receptor (EGFR) is a proto-oncogene commonly dysregulated in several cancers including non-small cell lung carcinoma (NSCLC) and, thus, is targeted for treatment using tyrosine kinase inhibitors (TKI) such as erlotinib. However, despite the efficacy observed in patients with NSCLC harboring oncogenic variants of the EGFR, general ineffectiveness of TKIs in patients with NSCLC who are current and former smokers necessitates identification of novel mechanisms to overcome this phenomenon. Previously, we showed that NSCLC cells harboring either wild-type (WT) EGFR or oncogenic mutant (MT) L858R EGFR become resistant to the effects of TKIs when exposed to cigarette smoke, evidenced by their autophosphorylation and prolonged downstream signaling. Here, we present Src as a target mediating cigarette smoke-induced resistance to TKIs in both WT EGFR- and L858R MT EGFR-expressing NSCLC cells. First, we show that cigarette smoke exposure of A549 cells leads to time-dependent activation of Src, which then abnormally binds to the WT EGFR causing TKI resistance, contrasting previous observations of constitutive binding between inactive Src and TKI-sensitive L858R MT EGFR. Next, we show that Src inhibition restores TKI sensitivity in cigarette smoke-exposed NSCLC cells, preventing EGFR autophosphorylation in the presence of erlotinib. Furthermore, we show that overexpression of a dominant-negative Src (Y527F/K295R) restores TKI sensitivity to A549 exposed to cigarette smoke. Importantly, the TKI resistance that emerges even in cigarette smoke-exposed L858R EGFR-expressing NSCLC cells could be eliminated with Src inhibition. Together, these findings offer new rationale for using Src inhibitors for treating TKI-resistant NSCLC commonly observed in smokers.

  2. Beta-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage and squamous metaplasia in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In epidemiologic studies, high intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of beta-cryptoxanthin on cigarette smoke-induced lung ...

  3. Atorvastatin and Simvastatin Promoted Mouse Lung Repair After Cigarette Smoke-Induced Emphysema.

    PubMed

    Pinho-Ribeiro, Vanessa; Melo, Adriana Correa; Kennedy-Feitosa, Emanuel; Graca-Reis, Adriane; Barroso, Marina Valente; Cattani-Cavalieri, Isabella; Carvalho, Giovanna Marcella Cavalcante; Zin, Walter Araújo; Porto, Luis Cristóvão; Gitirana, Lycia Brito; Lanzetti, Manuella; Valença, Samuel Santos

    2017-03-01

    Cigarette smoke (CS) induces pulmonary emphysema by inflammation, oxidative stress, and metalloproteinase (MMP) activation. Pharmacological research studies have not focused on tissue repair after the establishment of emphysema but have instead focused on inflammatory stimulation. The aim of our study was to analyze the effects of atorvastatin and simvastatin on mouse lung repair after emphysema caused by CS. Male mice (C57BL/6, n = 45) were divided into the following groups: control (sham-exposed), CSr (mice exposed to 12 cigarettes a day for 60 days and then treated for another 60 days with the vehicle), CSr+A (CSr mice treated with atorvastatin for 60 days), and CSr+S (CSr mice treated with simvastatin for 60 days). The treatment with atorvastatin and simvastatin was administered via inhalation (15 min with 1 mg/mL once a day). Mice were sacrificed 24 h after the completion of the 120-day experimental procedure. We performed biochemical, morphological, and physiological analyses. We observed decreased levels of leukocytes and cytokines in statin-treated mice, accompanied by a reduction in oxidative stress markers. We also observed a morphological improvement confirmed by a mean linear intercept counting in statin-treated mice. Finally, statins also ameliorated lung function. We conclude that inhaled atorvastatin and simvastatin improved lung repair after cigarette smoke-induced emphysema in mice.

  4. Soluble extracellular Klotho decreases sensitivity to cigarette smoke induced cell death in human lung epithelial cells.

    PubMed

    Blake, David J; Reese, Caitlyn M; Garcia, Mario; Dahlmann, Elizabeth A; Dean, Alexander

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the US and is associated with an abnormal inflammatory response to cigarette smoke (CS). Exposure to CS induces oxidative stress and can result in cellular senescence in the lung. Cellular senescence can then lead to decreased proliferation of epithelial cells, the destruction of alveolar structure and pulmonary emphysema. The anti-aging gene, klotho, encodes a membrane bound protein that has been shown to be a key regulator of oxidative stress and cellular senescence. In this study the role of Klotho (KL) with regard to oxidative stress and cellular senescence was investigated in human pulmonary epithelial cells exposed to cigarette smoke. Individual clones that stably overexpress Klotho were generated through retroviral transfection and geneticin selection. Klotho overexpression was confirmed through RT-qPCR, Western blotting and ELISA. Compared to control cells, constitutive Klotho overexpression resulted in decreased sensitivity to cigarette smoke induced cell death in vitro via a reduction of reactive oxygen species and a decrease in the expression of p21. Our results suggest that increasing Klotho level in pulmonary epithelial cells may be a promising strategy to reduce cellular senescence and mitigate the risk for the development of COPD.

  5. Forsythiaside inhibits cigarette smoke-induced lung inflammation by activation of Nrf2 and inhibition of NF-κB.

    PubMed

    Cheng, Li; Li, Fan; Ma, Rui; Hu, Xianping

    2015-09-01

    Cigarette smoke has been reported to be the major cause of chronic obstructive pulmonary disease (COPD). It causes persistent inflammation by regulating the redox-sensitive pathways. Forsythiaside, an active constituent isolated from the Chinese medicinal herb Forsythia suspensa, has been reported to have anti-inflammatory and anti-oxidant effects. Thus, in this study, we investigated the protective effects of forsythiaside against cigarette smoke-induced lung inflammation in mice. COPD mice model was established by cigarette smoke. Forsythiaside was given 2h before cigarette smoke exposure for five consecutive days. Bronchoalveolar lavage fluid and lung tissues were collected to assess pathological changes, lipid peroxidation, inflammatory cytokine production, Nrf-2, and NF-κB expression. Our results showed that forsythiaside attenuated the infiltration of inflammatory cells, NO and inflammatory cytokines TNF-α, IL-6 and IL-1β production, and reversed the CS-induced decrease of glutathione/glutathione disulfide (GSH/GSSG) ratio. Western blot analysis showed that forsythiaside inhibited cigarette smoke-induced NF-κB activation. In addition, forsythiaside dose-dependently up-regulated the expression of Nrf2 and HO-1. In conclusion, forsythiaside protected against cigarette smoke-induced lung injury through activating Nrf2 and inhibiting NF-κB signaling pathway.

  6. Hormonal changes accompanying cigarette smoke-induced preterm births in a mouse model.

    PubMed

    Ng, Sheung P; Steinetz, Bernard G; Lasano, Salamia G; Zelikoff, Judith T

    2006-09-01

    Epidemiologic evidence indicates that maternal smoking increases the risk of preterm birth. While a number of plausible mechanisms for early delivery have been offered, the role of gestational hormones in this smoke-induced outcome is uncertain. Thus, a toxicologic study was performed to examine the effects and underlying hormonal mechanisms of mainstream cigarette smoke (MCS) exposure on gestational duration. Pregnant B6C3F1 mice were exposed by inhalation to MCS for 5 days/week (4 hrs/day) from Gestational Day (GD) 4 to parturition. Smoke-induced effects on gestational length, interpubic ligament length, maternal hormone secretion patterns (estradiol-17beta, progesterone, prolactin, and relaxin), body weight gain, postimplantation loss, litter size, and offspring sex ratio were examined. Dams exposed to MCS at a concentration equivalent to smoking less than one pack of cigarettes/day (carbon monoxide = 25 parts per million, total suspended particulates = 16 mg/m3) demonstrated a significant (P < 0.05) shortening of gestational duration (compared with pregnant, air-exposed mice). In addition, MCS-exposed mice sacrificed on GD 18 had significantly (P < 0.05) increased interpubic ligament length, elevated serum estrogen levels, and a reduced progesterone to estradiol-17beta ratio (compared with air-exposed controls); levels of progesterone and prolactin were only modestly decreased and increased, respectively, in the MCS-exposed mice. Smoke exposure had no significant effects on maternal relaxin levels, body weight gain, postimplantation loss, litter size, or sex ratio. Results of this study demonstrate that inhalation exposure of pregnant mice to a low dose of MCS shortens gestation and alters hormone secretory patterns, which are important for maintaining pregnancy and inducing parturition. These findings support the view that pregnant women who smoke (even modestly) may be at increased risk for preterm birth, and that early delivery may be related (at least

  7. Heme oxygenase-1 alleviates cigarette smoke-induced restenosis after vascular angioplasty by attenuating inflammation in rat model.

    PubMed

    Ni, Leng; Wang, Zhanqi; Yang, Genhuan; Li, Tianjia; Liu, Xinnong; Liu, Changwei

    2016-03-14

    Cigarette smoke is not only a profound independent risk factor of atherosclerosis, but also aggravates restenosis after vascular angioplasty. Heme oxygenase-1 (HO-1) is an endogenous antioxidant and cytoprotective enzyme. In this study, we investigated whether HO-1 upregulating by hemin, a potent HO-1 inducer, can protect against cigarette smoke-induced restenosis in rat's carotid arteries after balloon injury. Results showed that cigarette smoke exposure aggravated stenosis of the lumen, promoted infiltration of inflammatory cells, and induced expression of inflammatory cytokines and adhesion molecules after balloon-induced carotid artery injury. HO-1 upregulating by hemin treatment reduced these effects of cigarette smoke, whereas the beneficial effects were abolished in the presence of Zincprotoporphyrin IX, an HO-1 inhibitor. To conclude, hemin has potential therapeutic applications in the restenosis prevention after the smokers' vascular angioplasty.

  8. Cigarette smoke induces aberrant EGF receptor activation that mediates lung cancer development and resistance to tyrosine kinase inhibitors.

    PubMed

    Filosto, Simone; Becker, Cathleen R; Goldkorn, Tzipora

    2012-04-01

    The EGF receptor (EGFR) and its downstream signaling are implicated in lung cancer development. Therefore, much effort was spent in developing specific tyrosine kinase inhibitors (TKI) that bind to the EGFR ATP-pocket, blocking EGFR phosphorylation/signaling. Clinical use of TKIs is effective in a subset of lung cancers with mutations in the EGFR kinase domain, rendering the receptor highly susceptible to TKIs. However, these benefits are limited, and emergence of additional EGFR mutations usually results in TKI resistance and disease progression. Previously, we showed one mechanism linking cigarette smoke to EGFR-driven lung cancer. Specifically, exposure of lung epithelial cells to cigarette smoke-induced oxidative stress stimulates aberrant EGFR phosphorylation/activation with impaired receptor ubiquitination/degradation. The abnormal stabilization of the activated receptor leads to uncontrolled cell growth and tumorigenesis. Here, we describe for the first time a novel posttranslational mechanism of EGFR resistance to TKIs. Exposure of airway epithelial cells to cigarette smoke causes aberrant phosphorylation/activation of EGFR, resulting in a conformation that is different from that induced by the ligand EGF. Unlike EGF-activated EGFR, cigarette smoke-activated EGFR binds c-Src and caveolin-1 and does not undergo canonical dimerization. Importantly, the cigarette smoke-activated EGFR is not inhibited by TKIs (AG1478; erlotinib; gefitinib); in fact, the cigarette smoke exposure induces TKI-resistance even in the TKI-sensitive EGFR mutants. Our findings show that cigarette smoke exposure stimulates not only aberrant EGFR phosphorylation impairing receptor degradation, but also induces a different EGFR conformation and signaling that are resistant to TKIs. Together, these findings offer new insights into cigarette smoke-induced lung cancer development and TKI resistance.

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

    PubMed

    Yang, Gen-Huan; Li, Yan-Chuan; Wang, Zhan-Qi; Liu, Bao; Ye, Wei; Ni, Leng; Zeng, Rong; Miao, Shi-Ying; Wang, Lin-Fang; Liu, Chang-Wei

    2014-11-01

    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.

  10. Cigarette smoke-induced lung emphysema in mice is associated with prolyl endopeptidase, an enzyme involved in collagen breakdown

    PubMed Central

    Koelink, Pim J.; Henricks, Paul A. J.; Jackson, Patricia L.; Nijkamp, Frans P.; Garssen, Johan; Kraneveld, Aletta D.; Blalock, J. Edwin; Folkerts, Gert

    2011-01-01

    There is increasing evidence that the neutrophil chemoattractant proline-glycine-proline (PGP), derived from the breakdown of the extracellular matrix, plays an important role in neutrophil recruitment to the lung. PGP formation is a multistep process involving neutrophils, metalloproteinases (MMPs), and prolyl endopeptidase (PE). This cascade of events is now investigated in the development of lung emphysema. A/J mice were whole body exposed to cigarette smoke for 20 wk. After 20 wk or 8 wk after smoking cessation, animals were killed, and bronchoalveolar lavage fluid and lung tissue were collected to analyze the neutrophilic airway inflammation, the MMP-8 and MMP-9 levels, the PE activity, and the PGP levels. Lung tissue degradation was assessed by measuring the mean linear intercept. Additionally, we investigated the effect of the peptide l-arginine-threonine-arginine (RTR), which binds to PGP sequences, on the smoke-induced neutrophil influx in the lung after 5 days of smoke exposure. Neutrophilic airway inflammation was induced by cigarette smoke exposure. MMP-8 and MMP-9 levels, PE activity, and PGP levels were elevated in the lungs of cigarette smoke-exposed mice. PE was highly expressed in epithelial and inflammatory cells (macrophages and neutrophils) in lung tissue of cigarette smoke-exposed mice. After smoking cessation, the neutrophil influx, the MMP-8 and MMP-9 levels, the PE activity, and the PGP levels were decreased or reduced to normal levels. Moreover, RTR inhibited the smoke-induced neutrophil influx in the lung after 5 days' smoke exposure. In the present murine model of cigarette smoke-induced lung emphysema, it is demonstrated for the first time that all relevant components (neutrophils, MMP-8, MMP-9, PE) involved in PGP formation from collagen are upregulated in the airways. Together with MMPs, PE may play an important role in the formation of PGP and thus in the pathophysiology of lung emphysema. PMID:21112944

  11. Mitochondrial E3 Ubiquitin Protein Ligase 1 Mediates Cigarette Smoke-Induced Endothelial Cell Death and Dysfunction.

    PubMed

    Kim, Sun-Yong; Kim, Hyo Jeong; Park, Mi Kyeong; Huh, Jin Won; Park, Hye Yun; Ha, Sang Yun; Shin, Joo-Ho; Lee, Yun-Song

    2016-02-01

    By virtue of the critical roles of Akt in vascular endothelial cell (EC) survival and function, cigarette smoke-induced Akt reduction may contribute to EC death and dysfunction in smokers' lungs. One of the negative Akt regulatory mechanisms is K48-linked Akt ubiquitination and subsequent proteasomal degradation. Here, we assessed the involvement of mitochondrial E3 ubiquitin protein ligase 1 (MUL1), recently revealed as a novel Akt ubiquitin E3 ligase, in cigarette smoke-induced Akt ubiquitination and its contribution to pulmonary EC death and dysfunction. In human lung microvascular ECs (HLMVECs), cigarette smoke extract (CSE) noticeably elevated MUL1 expression and K48-linked Akt ubiquitination, whereas Akt, p-Akt, eNOS, and p-eNOS levels were decreased. MUL1 knockdown suppressed CSE-induced Akt ubiquitination/degradation and cytoplasmic reductions of Akt and p-Akt. Furthermore, MUL1 knockdown attenuated reductions of eNOS and p-eNOS and alleviated EC survival, migration, and tube formation in the presence of CSE exposure. In addition, overexpression of K284R Akt, a mutant for a MUL1-ubiquitination site, produced similar effects. In HLMVECs exposed to CSE, Akt-MUL1 interaction was increased in coimmunoprecipitation and in situ proximity ligation assays. Similarly, the proximity ligation assay signals were elevated in rat lungs exposed to cigarette smoke for 3 months, during which Mul1 levels were noticeably increased. Finally, we found that CSE-mediated MUL1 induction in HLMVECs is mediated by retinoic acid receptor-related orphan receptor α. Taken together, these data suggest that cigarette smoke-induced MUL1 elevation mediates Akt ubiquitination/degradation, potentially leading to pulmonary EC death and functional impairment.

  12. MUC1 in macrophage contributions to cigarette smoke-induced lung cancer

    PubMed Central

    Xu, Xiuling; Padilla, Mabel T.; Li, Bilan; Wells, Alexandria; Kato, Kosuke; Tellez, Carmen; Belinsky, Steven A.; Kim, Kwang Chul; Lin, Yong

    2013-01-01

    Expression of the pro-oncogenic mucin MUC1 is elevated by inflammation in airway epithelial cells, but the contributions of MUC1 to the development of lung cancer are uncertain. In this study, we developed our finding that cigarette smoke (CS) increases Muc1 expression in lung macrophages, where we hypothesized it might contribute to CS-induced transformation of bronchial epithelial cells. In human macrophages, CS extract (CSE) strongly induced MUC1 expression through a mechanism involving the nuclear receptor PPAR-γ. CSE-induced ERK activation was also required for MUC1 expression, but it had little effect on MUC1 transcription. RNAi-mediated attenuation of MUC1 suppressed CSE-induced secretion of TNF-α from macrophages, by suppressing the activity of the TNF-α processing enzyme TACE, arguing that MUC1 is required for CSE-induced and TACE-mediated TNF-α secretion. Similarly, MUC1 blockade after CSE induction through suppression of PPAR-γ or ERK inhibited TACE activity and TNF-α secretion. Conditioned media from CSE-treated macrophages induced MUC1 expression and potentiated CSE-induced transformation of human bronchial epithelial cells (HBEC) in a TNF-α-dependent manner. Together, our results identify a signaling pathway involving PPAR-γ, ERK and MUC1 that is used by CSE to trigger TNF-α secretion from macrophages. Further, our results show how that MUC1 contributes to smoking-induced lung cancers that are driven by inflammatory signals driven by macrophages PMID:24282280

  13. Cigarette Smoking-Induced Cardiac Hypertrophy, Vascular Inflammation and Injury Are Attenuated by Antioxidant Supplementation in an Animal Model

    PubMed Central

    Al Hariri, Moustafa; Zibara, Kazem; Farhat, Wissam; Hashem, Yasmine; Soudani, Nadia; Al Ibrahim, Farah; Hamade, Eva; Zeidan, Asad; Husari, Ahmad; Kobeissy, Firas

    2016-01-01

    Background: Cardiovascular diseases are the leading causes of morbidity and mortality worldwide. Cigarette smoking remains a global health epidemic with associated detrimental effects on the cardiovascular system. In this work, we investigated the effects of cigarette smoke exposure on cardiovascular system in an animal model. The study then evaluated the effects of antioxidants (AO), represented by pomegranate juice, on cigarette smoke induced cardiovascular injury. This study aims at evaluating the effect of pomegranate juice supplementation on the cardiovascular system of an experimental rat model of smoke exposure. Methods: Adult rats were divided into four different groups: Control, Cigarette smoking (CS), AO, and CS + AO. Cigarette smoke exposure was for 4 weeks (5 days of exposure/week) and AO group received pomegranate juice while other groups received placebo. Assessment of cardiovascular injury was documented by assessing different parameters of cardiovascular injury mediators including: (1) cardiac hypertrophy, (2) oxidative stress, (3) expression of inflammatory markers, (4) expression of Bradykinin receptor 1 (Bdkrb1), Bradykinin receptor 2 (Bdkrb2), and (5) altered expression of fibrotic/atherogenic markers [(Fibronectin (Fn1) and leptin receptor (ObR))]. Results: Data from this work demonstrated that cigarette smoke exposure induced cardiac hypertrophy, which was reduced upon administration of pomegranate in CS + AO group. Cigarette smoke exposure was associated with elevation in oxidative stress, significant increase in the expression of IL-1β, TNFα, Fn1, and ObR in rat's aorta. In addition, an increase in aortic calcification was observed after 1 month of cigarette smoke exposure. Furthermore, cigarette smoke induced a significant up regulation in Bdkrb1 expression level. Finally, pomegranate supplementation exhibited cardiovascular protection assessed by the above findings and partly contributed to ameliorating cardiac hypertrophy in cigarette

  14. The involvement of serotonin metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo.

    PubMed

    Lau, Way Kwok-Wai; Li, Xiang; Yeung, Dave Sze-Chun; Chan, Ka-Ho; Ip, Mary Sau-Man; Mak, Judith Choi-Wo

    2012-11-01

    Recently, we have reported the dysregulation of circulating serotonin (5-hydroxytryptamine, 5-HT) homeostasis in patients with chronic obstructive pulmonary disease (COPD). An increase in metabolism of 5-HT has been reported to induce oxidative stress via monoamine oxidase (MAO)-dependent pathway. The present study aimed at investigating the effect of cigarette smoke exposure on the systemic circulation and local airway 5-HT levels as well as MAO-mediated oxidative pathway using a cigarette smoke-exposed rat model. Male Sprague-Dawley rats (150-200 g) were exposed to either sham air or 4% (v/v, smoke/air) cigarette smoke for 1 hour daily for 56 consecutive days. Sera, bronchoalveolar larvage (BAL) and lung tissues were collected 24 hours after the last exposure. We found a significant reduction in the reduced glutathione (rGSH) and an elevation in advanced oxidation protein products (AOPP), a protein oxidation marker, in the lung of cigarette smoke-exposed group (p < 0.05). A significant increase in 5-HT was found in serum (p < 0.05), but not in the BAL or lung, after cigarette smoke exposure. MAO-A activity was significantly elevated in the lung of cigarette smoke-exposed group (p < 0.05). Furthermore, increased superoxide anion levels were found in lung homogenates of cigarette smoke-exposed rats after incubation with 5-HT (p < 0.05), which was positively associated with the increase in MAO-A activity (r = 0.639, p < 0.05). Our findings supported the presence of GSH disruption and protein oxidation in the lung after cigarette smoke exposure. The metabolism of 5-HT by MAO-A in the lung enhanced cigarette smoke-induced superoxides, which might contribute to the pathogenesis of COPD.

  15. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    PubMed

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; de Oliveira, Ana Paula Ligeiro

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

  16. Effect of simvastatin on MMPs and TIMPs in cigarette smoke-induced rat COPD model

    PubMed Central

    Sun, Jiawei; Bao, Jie; Shi, Yanan; Zhang, Bin; Yuan, Lindong; Li, Junhong; Zhang, Lihai; Sun, Mo; Zhang, Ling; Sun, Wuzhuang

    2017-01-01

    /L, P<0.01). CSE resulted in significantly increased accumulation of neutrophils and macrophages (neutrophils: 14.5%±1.3% of CSE group vs 9.1%±1.5% of control; macrophage: 91%±3% of CSE group vs 87%±2% of control, P<0.05), and simvastatin significantly reduced neutrophils (12.9%±2.0%, P<0.05) in the bronchoalveolar lavage fluid, but had no effect on macrophage (89%±1.6%, P>0.05). In response to CSE, MMP-8, MMP-9, and MMP-12 mRNA were upregulated more than sevenfold, while TIMP-1 and TIMP-4 increased two- to fivefold. Simvastatin significantly blocked upregulation of MMP-8 and -9 (P<0.01), but had no effect on MMP-12, TIMP-1 and TIMP-4 mRNA (P>0.05). In addition, simvastatin significantly blocked cigarette smoke-induced MMP-8 and -9 protein synthesis, while it had no significant effect on TIMP-1 and -4 protein synthesis even in the presence of cigarette smoke. Conclusion CSE resulted in imbalance of MMPs and TIMPs, and by which mechanism, cigarette smoke may lead to insufficient lung tissue repair. Simvastatin partially blocked airway inflammation and MMP production and, thus, statins may modulate composition of the lung extracellular matrix. PMID:28260878

  17. Aquaporin 5 regulates cigarette smoke induced emphysema by modulating barrier and immune properties of the epithelium.

    PubMed

    Aggarwal, Neil R; Chau, Eric; Garibaldi, Brian T; Mock, Jason R; Sussan, Thomas; Rao, Keshav; Rao, Kaavya; Menon, Anil G; D'Alessio, Franco R; Damarla, Mahendra; Biswal, Shyam; King, Landon S; Sidhaye, Venkataramana K

    2013-10-01

    Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality. Cigarette smoke, the most common risk factor for COPD, induces airway and alveolar epithelial barrier permeability and initiates an innate immune response. Changes in abundance of aquaporin 5 (AQP5), a water channel, can affect epithelial permeability and immune response after cigarette smoke exposure. To determine how AQP5-derived epithelial barrier modulation affects epithelial immune response to cigarette smoke and development of emphysema, WT and AQP5(-/-) mice were exposed to cigarette smoke (CS). We measured alveolar cell counts and differentials, and assessed histology, mean-linear intercept (MLI), and surface-to-volume ratio (S/V) to determine severity of emphysema. We quantified epithelial-derived signaling proteins for neutrophil trafficking, and manipulated AQP5 levels in an alveolar epithelial cell line to determine specific effects on neutrophil transmigration after CS exposure. We assessed paracellular permeability and epithelial turnover in response to CS. In contrast to WT mice, AQP5(-/-) mice exposed to 6 months of CS did not demonstrate a significant increase in MLI or a significant decrease in S/V compared with air-exposed mice, conferring protection against emphysema. After sub-acute (4 weeks) and chronic (6 mo) CS exposure, AQP5(-/-) mice had fewer alveolar neutrophil but similar lung neutrophil numbers as WT mice. The presence of AQP5 in A549 cells, an alveolar epithelial cell line, was associated with increase neutrophil migration after CS exposure. Compared with CS-exposed WT mice, neutrophil ligand (CD11b) and epithelial receptor (ICAM-1) expression were reduced in CS-exposed AQP5(-/-) mice, as was secreted LPS-induced chemokine (LIX), an epithelial-derived neutrophil chemoattractant. CS-exposed AQP5(-/-) mice demonstrated decreased type I pneumocytes and increased type II pneumocytes compared with CS-exposed WT mice suggestive of enhanced epithelial

  18. Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF-κB activation.

    PubMed

    Ma, Jianqun; Xu, Hai; Wu, Jun; Qu, Changfa; Sun, Fenglin; Xu, Shidong

    2015-12-01

    Linalool, a natural compound that exists in the essential oils of several aromatic plants species, has been reported to have anti-inflammatory effects. However, the effects of linalool on cigarette smoke (CS)-induced acute lung inflammation have not been reported. In the present study, we investigated the protective effects of linalool on CS-induced acute lung inflammation in mice. Linalool was given i.p. to mice 2h before CS exposure daily for five consecutive days. The numbers of macrophages and neutrophils in bronchoalveolar lavage fluid (BALF) were measured. The production of TNF-α, IL-6, IL-1β, IL-8 and MCP-1 were detected by ELISA. The expression of NF-κB was detected by Western blotting. Our results showed that treatment of linalool significantly attenuated CS-induced lung inflammation, coupled with inhibited the infiltration of inflammatory cells and TNF-α, IL-6, IL-1β, IL-8 and MCP-1 production. Meanwhile, treatment of linalool inhibited CS-induced lung MPO activity and pathological changes. Furthermore, linalool suppressed CS-induced NF-κB activation in a dose-dependent manner. In conclusion, our results demonstrated that linalool protected against CS-induced lung inflammation through inhibiting CS-induced NF-κB activation.

  19. Genetic Ablation of CXCR2 Protects against Cigarette Smoke-Induced Lung Inflammation and Injury

    PubMed Central

    Lerner, Chad A.; Lei, Wei; Sundar, Isaac K.; Rahman, Irfan

    2016-01-01

    Antagonism of CXCR2 receptors, predominately located on neutrophils and critical for their immunomodulatory activity, is an attractive pharmacological therapeutic approach aimed at reducing the potentially damaging effects of heightened neutrophil influx into the lung. The role CXCR2 in lung inflammation in response to cigarette smoke (CS) inhalation using the mutant mouse approach is not known. We hypothesized that genetic ablation of CXCR2 would protect mice against CS-induced inflammation and DNA damage response. We used CXCR2−/− deficient/mutant (knock-out, KO) mice, and assessed the changes in critical lung inflammatory NF-κB-driven chemokines released from the parenchyma of CS-exposed mice. The extent of tissue damage was assessed by the number of DNA damaging γH2AX positive cells. CXCR2 KO mice exhibited protection from heightened levels of neutrophils measured in BALF taken from mice exposed to CS. IL-8 (KC mouse) levels in the BALF from CS-exposed CXCR2 KO were elevated compared to WT. IL-6 levels in BALF were refractory to increase by CS in CXCR2 KO mice. There were no significant changes to MIP-2, MCP-1, or IL-1β. Total levels of NF-κB were maintained at lower levels in CS-exposed CXCR2 KO mice compared to WT mice exposed to CS. Finally, CXCR2 KO mice were protected from lung cells positive for DNA damage response and senescence marker γH2AX. CXCR2 KO mice are protected from heightened inflammatory response mediated by increased neutrophil response as a result of acute 3 day CS exposure. This is also associated with changes in pro-inflammatory chemokines and reduced incursion of γH2AX indicating CXCR2 deficient mice are protected from lung injury. Thus, CXCR2 may be a pharmacological target in setting of inflammation and DNA damage in the pathogenesis of COPD. PMID:27826243

  20. Proteomic Profiling of Cigarette Smoke Induced Changes in Retinal Pigment Epithelium Cells.

    PubMed

    Merl-Pham, Juliane; Gruhn, Fabian; Hauck, Stefanie M

    2016-01-01

    Age-related macular degeneration (AMD) is a medical condition usually affecting older adults and resulting in a loss of vision in the macula, the center of the visual field. The dry form of this disease presents with atrophy of the retinal pigment epithelium, resulting in the detachment of the retina and loss of photoreceptors. Cigarette smoke is one main risk factor for dry AMD and increases the risk of developing the disease by three times. In order to understand the influence of cigarette smoke on retinal pigment epithelial cells, cultured human ARPE-19 cells were treated with cigarette smoke extract for 24 h. Using quantitative mass spectrometry more than 3000 proteins were identified and their respective abundances were compared between cigarette smoke-treated and untreated cells. Altogether 1932 proteins were quantified with at least two unique peptides, with 686 proteins found to be significantly differentially abundant with p > 0.05. Of these proteins the abundance of 64 proteins was at least 2-fold down-regulated after cigarette smoke treatment while 120 proteins were 2-fold up-regulated. The analysis of associated biological processes revealed an alteration of proteins involved in RNA processing and transport as well as extracellular matrix remodelling in response to cigarette smoke treatment.

  1. Smoking-Induced Acute Eosinophilic Pneumonia in a 15-year-old Girl: A Case Report

    PubMed Central

    Youn, Ji-Seok; Kwon, Ji-Won; Kim, Byoung-Ju

    2010-01-01

    Acute eosinophilic pneumonia is a very rare disease that is characterized by acute febrile respiratory failure, diffuse bilateral infiltrates on chest X-ray, and eosinophilia in bronchoalveolar lavage fluid in the absence of infection. We present the case of a 15-year-old girl diagnosed with smoking-induced acute eosinophilic pneumonia. A previously healthy young girl with a 1-day history of fever presented with cough, dyspnea, and diffuse bilateral infiltrates on chest X-ray. She had started smoking only 3 weeks before presentation. She was diagnosed by bronchoalveolar lavage fluid tests and lung biopsy and dramatically improved after steroid treatment. We emphasize that acute eosinophilic pneumonia must be considered when acute pneumonia does not respond to broad-spectrum antibiotics. Effective treatment and prompt institution of therapy can obviate unnecessary morbidity and mortality. PMID:20358030

  2. Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression

    PubMed Central

    Hays, L E; Zodrow, D M; Yates, J E; Deffebach, M E; Jacoby, D B; Olson, S B; Pankow, J F; Bagby, G C

    2008-01-01

    Chromosomal abnormalities are commonly found in bronchogenic carcinoma cells, but the molecular causes of chromosomal instability (CIN) and their relationship to cigarette smoke has not been defined. Because the Fanconi anaemia (FA)/BRCA pathway is essential for maintenance of chromosomal stability, we tested the hypothesis that cigarette smoke suppresses that activity of this pathway. Here, we show that cigarette smoke condensate (CSC) inhibited translation of FANCD2 mRNA (but not FANCC or FANCG) in normal airway epithelial cells and that this suppression of FANCD2 expression was sufficient to induce both genetic instability and programmed cell death in the exposed cell population. Cigarette smoke condensate also suppressed FANCD2 function and induced CIN in bronchogenic carcinoma cells, but these cells were resistant to CSC-induced apoptosis relative to normal airway epithelial cells. We, therefore, suggest that CSC exerts pressure on airway epithelial cells that results in selection and emergence of genetically unstable somatic mutant clones that may have lost the capacity to effectively execute an apoptotic programme. Carcinogen-mediated suppression of FANCD2 gene expression provides a plausible molecular mechanism for CIN in bronchogenic carcinogenesis. PMID:18475298

  3. Modeling the influence of vitamin D deficiency on cigarette smoke-induced emphysema

    PubMed Central

    Crane-Godreau, Mardi A.; Black, Candice C.; Giustini, Andrew J.; Dechen, Tenzin; Ryu, Jihan; Jukosky, James A.; Lee, Hong-Kee; Bessette, Katherine; Ratcliffe, Nora R.; Hoopes, P. Jack; Fiering, Steven; Kelly, John A.; Leiter, J. C.

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. While the primary risk factor for COPD is cigarette smoke exposure, vitamin D deficiency has been epidemiologically implicated as a factor in the progressive development of COPD-associated emphysema. Because of difficulties inherent to studies involving multiple risk factors in the progression of COPD in humans, we developed a murine model in which to study the separate and combined effects of vitamin D deficiency and cigarette smoke exposure. During a 16-week period, mice were exposed to one of four conditions, control diet breathing room air (CD-NS), control diet with cigarette smoke exposure (CD-CSE), vitamin D deficient diet breathing room air (VDD-NS) or vitamin D deficient diet with cigarette smoke exposure (VDD-CSE). At the end of the exposure period, the lungs were examined by a pathologist and separately by morphometric analysis. In parallel experiments, mice were anesthetized for pulmonary function testing followed by sacrifice and analysis. Emphysema (determined by an increase in alveolar mean linear intercept length) was more severe in the VDD-CSE mice compared to control animals and animals exposed to VDD or CSE alone. The VDD-CSE and the CD-CSE mice had increased total lung capacity and increased static lung compliance. There was also a significant increase in the matrix metalloproteinase-9: tissue inhibitor of metalloproteinases-1 (TIMP-1) ratio in VDD-CSE mice compared with all controls. Alpha-1 antitrypsin (A1AT) expression was reduced in VDD-CSE mice as well. In summary, vitamin D deficiency, when combined with cigarette smoke exposure, seemed to accelerate the appearance of emphysemas, perhaps by virtue of an increased protease-antiprotease ratio in the combined VDD-CSE animals. These results support the value of our mouse model in the study of COPD. PMID:23781205

  4. Cigarette smoke-induced DNA adducts in the respiratory and nonrespiratory tissues of rats

    SciTech Connect

    Gairola, C.G.; Gupta, R.C. )

    1991-01-01

    Formation of DNA adducts is regarded as an essential initial step in the process of chemical carcinogenesis. To determine how chronic exposure to cigarette smoke affects the distribution of DNA adducts in selected respiratory and nonrespiratory tissues. The authors exposed male Sprague-Dawley rats daily to fresh mainstream smoke from the Univ. of Kentucky reference cigarettes (2R1) in a nose-only exposure system for 32 weeks. Blood carboxyhemoglobin, total particulate matter (TPM) intake, and pulmonary aryl hydrocarbon hydroxylase values indicated effective exposure of animals to cigarette smoke. DNA was extracted from three respiratory (larynx, trachea, and lung) and three nonrespiratory (liver, heart, and bladder) tissues and analyzed for DNA adducts by the {sup 32}P-postlabeling assay under conditions capable of detecting low levels of diverse aromatic/hydrophobic adducts. Data showed that the total DNA adducts in the lung, heart, and trachea, and larynx were increased by 10- to 20-fold in the smoke-exposed group. These data suggest selective formation of DNA adducts in the tissues.

  5. Inhibition by oral N-acetylcysteine of cigarette smoke-induced "bronchitis" in the rat.

    PubMed

    Rogers, D F; Jeffery, P K

    1986-01-01

    Specific pathogen-free rats were exposed to the cigarette smoke (CS) of 25 cigarettes daily for 14 days and concurrently given N-acetylcysteine (Nac) as 1% of their drinking water (average daily dose 973 mg/kg). The thickness of the epithelium was measured at four airway levels and the numbers of mucus-containing secretory cells, stained for neutral or acidic glycoprotein (NGP or AGP respectively), were counted in surface epithelium at eight airway levels. Cigarette smoke increased the thickness of the epithelium at three of the airway levels studied by between 37 and 72%. The number of secretory cells was increased at all airway levels distal to the upper trachea by between 102 and 421%. Secretory cells containing NGP were reduced in number but this was more than offset by a large increase in the number of secretory cells containing AGP at all airway levels. N-acetylcysteine inhibited CS-induced epithelial thickening. Nac also inhibited the CS-induced increase in the number of secretory cells with AGP, but had little effect on the CS-induced reduction in the number of cells with NGP. Thus, prophylactic oral N-acetylcysteine led to an overall inhibition of CS-induced mucous cell hyperplasia and epithelial hypertrophy. The results suggest a novel anti-inflammatory action for a drug with known mucolytic effects.

  6. Cadmium-enriched cigarette smoke-induced cytological and biochemical alterations in rat lungs

    SciTech Connect

    Gairola, C.G. )

    1989-01-01

    Male Sprague-Dawley rats were exposed daily for 52 wk in a nose-only exposure system to smoke from the University of Kentucky 2R1 reference cigarettes (SM) or from cigarettes made of cadmium-enriched tobacco (Cd-SM). At sacrifice, the animals were evaluated by bronchoalveolar lavage (BAL) for inflammatory cell response in the lungs, and the cells so obtained were analyzed for phagocytosis of particles (latex and IgG-coated SRBCs) and for their ability to release oxidants upon phagocytic challenge. Additionally, lung tissues were analyzed for Cd levels and lung homogenate fractions were assayed for aryl hydrocarbon hydroxylase (AHH) as well as total and selenium-dependent glutathione peroxidase (GSH-Px) activities. BAL cell counts showed a significant influx of inflammatory cells into the lungs of the Cd-SM group but not the SM group. The proportion of neutrophils in the BAL cells of the Cd-Sm group was elevated to 40 {plus minus} 9%, compared with less than 2% in the SM group. Phagocytosis of both types of particles by macrophages from SM and Cd-SM groups was similar to that of the control groups, except that a greater uptake of latex particles was seen is Cd-SM macrophages. The release of oxidants (superoxides and hydrogen peroxide) by the BAL cells was severely impaired in the Cd-SM group, whereas a slight stimulation was seen in the SM gropu. Pulmonary GSH-Px activity was the same in all groups. A significant induction of the pulmonary AHH activity was observed in the SM group only. The Cd levels in the lungs were approximately 8- and 200-fold greater than controls in SM and Cd-SM groups, respectively. These observation suggest a significant influence of tabacco Cd on the toxicity of cigarette smoke.

  7. Implication of PDGF signaling in cigarette smoke-induced pulmonary arterial hypertension in rat.

    PubMed

    Xing, Ai-ping; Hu, Xiao-yun; Shi, Yi-wei; Du, Yong-cheng

    2012-07-01

    Pulmonary artery hypertension (PAH) is a severe disease characterized with progressive increase of pulmonary vascular resistance that finally causes right ventricular failure and premature death. Cigarette smoke (CS) is a major factor of Chronic Obstructive Pulmonary Disease (COPD) that can lead to PAH. However, the mechanism of CS-induced PAH is poorly understood. Mounting evidence supports that pulmonary vascular remodeling play an important role in the development of PAH. PDGF signaling has been demonstrated to be a major mediator of vascular remodeling implicated in PAH. However, the association of PDGF signaling with CS-induced PAH has not been documented. In this study, we investigated CS-induced PAH in rats and the expression of platelet derived growth factor (PDGF) and PDGF receptor (PDGFR) in pulmonary artery. Forty male rats were randomly divided into control group and three experimental groups that were exposed to CS for 1, 2, and 3 months, respectively. CS significantly increased right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI). Histology staining demonstrated that CS significantly increased the thickness of pulmonary artery wall and collagen deposition. The expression of PDGF isoform B (PDGF-B) and PDGF receptor beta (PDGFRβ) were significantly increased at both protein and mRNA levels in pulmonary artery of rats with CS exposure. Furthermore, Cigarette smoke extract (CSE) significantly increased rat pulmonary artery smooth muscle cell (PASMC) proliferation, which was inhibited by PDGFR inhibitor Imatinib. Thus, our data suggest PDGF signaling is implicated in CS-induced PAH.

  8. Sildenafil in a cigarette smoke-induced model of COPD in the guinea-pig.

    PubMed

    Domínguez-Fandos, David; Valdés, César; Ferrer, Elisabet; Puig-Pey, Raquel; Blanco, Isabel; Tura-Ceide, Olga; Paul, Tanja; Peinado, Víctor I; Barberà, Joan A

    2015-08-01

    Sildenafil, a phosphodiesterase-5 inhibitor used to treat pulmonary hypertension, may have effects on pulmonary vessel structure and function. We evaluated the effects of sildenafil in a cigarette smoke (CS)-exposed model of chronic obstructive pulmonary disease (COPD).42 guinea-pigs were exposed to cigarette smoke or sham-exposed and treated with sildenafil or vehicle for 12 weeks, divided into four groups. Assessments included respiratory resistance, pulmonary artery pressure (PAP), right ventricle (RV) hypertrophy, endothelial function of the pulmonary artery and lung vessel and parenchymal morphometry.CS-exposed animals showed increased PAP, RV hypertrophy, raised respiratory resistance, airspace enlargement and intrapulmonary vessel remodelling. CS exposure also produced wall thickening, increased contractility and endothelial dysfunction in the main pulmonary artery. CS-exposed animals treated with sildenafil showed lower PAP and a trend to less RV hypertrophy than CS-exposed only animals. Furthermore, sildenafil preserved the intrapulmonary vessel density and attenuated the airspace enlargement induced by CS. No differences in gas exchange, respiratory resistance, endothelial function and vessel remodelling were observed.We conclude that in this experimental model of COPD, sildenafil prevents the development of pulmonary hypertension and contributes to preserve the parenchymal and vascular integrity, reinforcing the notion that the nitric oxide-cyclic guanosine monophosphate axis is perturbed by CS exposure.

  9. Therapeutic Effects of Resveratrol in a Mouse Model of LPS and Cigarette Smoke-Induced COPD.

    PubMed

    Chen, Jinlong; Yang, Xu; Zhang, Weiya; Peng, Danhua; Xia, Yanan; Lu, Yi; Han, Xiaodong; Song, Guangjie; Zhu, Jing; Liu, Renping

    2016-12-01

    This study was designed to examine whether resveratrol exerts the protective effects on LPS and cigarette smoke (LC)-induced COPD in a murine model. In lung histopathological studies, H&E, Masson's trichrome, and AB-PAS staining were performed. The cytokines (IL-6, IL-17, TGF-β, and TNF-α) and inflammatory cells in BALF were determined. The Beclin1 level in the lungs of mouse was analyzed. Compared with the LC-induced mouse, the level of inflammatory cytokines (IL-17, IL-6, TNF-α, and TGF-β) of the BALF in the resveratrol + cigarette smoke-treated mouse had obviously decreased. Histological examination of the lung tissue revealed that the resveratrol treatment attenuated the fibrotic response and mucus hypersecretion. In addition, resveratrol inhibited the expression of the Beclin1 protein in mouse lungs. The presented findings collectively suggest that resveratrol has a therapeutic effect on mouse LC-induced COPD, and its mechanism of action might be related to reducing the production of the Beclin1 protein.

  10. Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

    PubMed Central

    Cloonan, Suzanne M.; Glass, Kimberly; Laucho-Contreras, Maria E.; Bhashyam, Abhiram R.; Cervo, Morgan; Pabón, Maria A.; Konrad, Csaba; Polverino, Francesca; Siempos, Ilias I.; Perez, Elizabeth; Mizumura, Kenji; Ghosh, Manik C.; Parameswaran, Harikrishnan; Williams, Niamh C.; Rooney, Kristen T.; Chen, Zhi-Hua; Goldklang, Monica P.; Yuan, Guo-Cheng; Moore, Stephen C.; Demeo, Dawn L.; Rouault, Tracey A.; D’Armiento, Jeanine M.; Schon, Eric A.; Manfredi, Giovanni; Quackenbush, John; Mahmood, Ashfaq; Silverman, Edwin K.; Owen, Caroline A.; Choi, Augustine M.K.

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. PMID:26752519

  11. Cigarette Smoke Induces Immune Responses to Vimentin in both, Arthritis-Susceptible and -Resistant Humanized Mice

    PubMed Central

    Bidkar, Mitali; Vassallo, Robert; Luckey, David; Smart, Michele; Mouapi, Kelly

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease marked by chronic synovial inflammation and both, genetic and environmental factors are involved in its pathogenesis. Human leukocyte antigen (HLA) DRB1*0401 is associated with susceptibility to develop RA, while cigarette smoke (CS) exposure promotes seropositive disease with increased severity in DRB1*0401+ individuals. Smokers have higher levels of antibodies against citrullinated peptides. In this study, we determined whether the response to a known autoantigen, Vimentin (Vim) is shared epitope specific and how CS influences this response using transgenic-mice carrying RA-susceptible,*0401, and -resistant, *0402, genes. Following relatively brief exposure to CS, peptidyl arginine deiminase (PAD) enzyme expression was increased in murine lungs. Cigarette smoking led to production of Interferon (IFN)-γ with reduced levels of Interleukin (IL)-10 by splenocytes of *0401 mice. In contrast, CS augmented Th2 cytokines along with T-regulatory cells in *0402 mice. An increase in levels of antibodies to native and citrullinated Vim was observed in naïve mice of both strains following CS exposure. Our data showed that both arthritis-susceptible and -resistant mice can generate cellular and humoral immunity to Vim; however CS-induced modulation of host immunity is dependent on the interaction with the host HLA genes. PMID:27602574

  12. Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

    PubMed Central

    Dey, Neekkan; Chattopadhyay, Dhruba J.; Chatterjee, Indu B.

    2011-01-01

    Lung cancer is the leading cause of cancer dearth. Cigarette smoking is the strongest risk factor for developing lung cancer, which is conceivably initiated by proliferation. Here, we show that low concentration of aqueous extract of cigarette smoke (AECS) causes excessive proliferation of human lung epithelial cells (A549) without any apoptotic cell death. The causative factor responsible for AECS-induced proliferation has been identified as p-benzoquinone (p-BQ). Coimmunoprecipitation and immunoblot experiments indicate that p-BQ binds with epidermal growth factor receptor (EGFR). However, in contrast to EGF, it causes aberrant phosphorylation of EGFR that lacks c-Cbl-mediated ubiquitination and degradation resulting in persistent activation of EGFR. This is followed by activation of Hras + Kras and the downstream survival and proliferative signaling molecules Akt and ERK1/2, as well as the nuclear transcription factors c-Myc and c-Fos. Vitamin C and/or antibody to p-BQ prevents AECS/p-BQ-induced proliferation of lung cells apparently by inactivating p-BQ and thereby preventing activation of EGFR and the downstream signaling molecules. The results suggest that vitamin C and/or antibody to p-BQ may provide a novel intervention for preventing initiation of lung cancer in smokers. PMID:21772844

  13. Antioxidant protective effect of honey in cigarette smoke-induced testicular damage in rats.

    PubMed

    Mohamed, Mahaneem; Sulaiman, Siti Amrah; Jaafar, Hasnan; Sirajudeen, Kuttulebbai Nainamohamed Salam

    2011-01-01

    Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis.

  14. Light cigarette smoke-induced emphysema and NFκB activation in mouse lung

    PubMed Central

    Santos Valenca, Samuel; Castro, Paulo; Alves Pimenta, Wagner; Lanzetti, Manuella; Vargas Silva, Simone; Barja-Fidalgo, Cristina; Gonçalves Koatz, Vera Lúcia; Porto, Luís Cristóvão

    2006-01-01

    Light cigarette (LC) exposure is supposed to be less hazardous with a decreased incidence of cancer and tobacco-associated diseases. C57BL/6 mouse groups were subjected to smoke from 3, 6 or 12 LC for 60 days and compared with mice exposed to ambient air (EAA) in order to study lung injury by morphometrical and biochemical methods. Bronchoalveolar lavage (BAL) analysis and histology and stereology were performed. Tissue from the right lung was used for measuring thiobarbituric acid reactive substances (TBARS) and Western blot analysis. One way anova was performed followed by the Student–Newman Keuls post-test (P < 0.05). The cellular content of BAL was 95% alveolar macrophages in all groups except in mice exposed to 3 LC, where 23% neutrophils were observed. Emphysema was not observed in three and 6 LC, but it was found in 12 LC parallel to increased volume density (Vv) of airspaces from 61.0 ± 0.6 (EAA) to 80.9 ± 1.0 (12 LC) and decreased Vv of elastic fibres from 17.8 ± 0.9 (EAA) to 11.8 ± 0.6 (12 LC). All exposed groups to LC showed low TBARS levels compared with mice EAA. Lung tissue from animals exposed to 12 LC showed decreased tissue inhibitor of metalloprotease-2 and increased matrix metalloprotease-12 detection, which suggests an imbalance in extracellular matrix (ECM). Increased tumour necrosis factor-α and nuclear factor-κB detection were observed in exposed groups to LC when compared with mice EAA. The data suggest that LC is so dangerous to lungs as full-flavour cigarettes inducing ECM imbalance and emphysema. PMID:16965565

  15. Platycodin D protects against cigarette smoke-induced lung inflammation in mice.

    PubMed

    Gao, Wei; Guo, Ying; Yang, Hongxia

    2017-03-28

    Cigarette smoke is the one of the major factors that leads to chronic obstructive pulmonary disease (COPD). Inflammation and oxidant stress have been known to play critical roles in the development of COPD. Platycodin D (PLD) has been reported to have anti-inflammatory and anti-oxidant effects. In this study, we aimed to investigate the protective effects of PLD on cigarette smoke (CS)-induced lung inflammation in mice. PLD was adminstrated i.p. to mice 2h before CS exposure daily for five consecutive days. The production of inflammatory cytokines TNF-α and IL-1β were measured by ELISA. The levels of malonaldehyde (MDA) and nitric oxide (NO) were also detected in this study. The expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NF-κB, and IκBα were detected by western blot analysis. The results showed that PLD significantly attenuated CS-induced lung pathological changes, inflammatory cells infiltration, as well as TNF-α and IL-1β production. CS-induced MDA and NO production were also inhibited by treatment of PLD. Western blot analysis showed that PLD significantly suppressed CS-induced NF-κB activation. In addition, PLD was found to increase the expression of Nrf2 and HO-1. Taken together, these results indicated that PLD protected against CS-induced lung inflammation by inhibiting inflammatory and oxidative response through activating Nrf2 signaling pathway. PLD might be an effective treatment for CS-induced lung inflammation.

  16. Eicosapentaenoic acid attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling

    PubMed Central

    Liu, Meng-Han; Lin, An-Hsuan; Lu, Shing-Hwa; Peng, Ruo-Yun; Lee, Tzong-Shyuan; Kou, Yu Ru

    2014-01-01

    Cigarette smoking causes chronic lung inflammation that is mainly regulated by redox-sensitive pathways. Our previous studies have demonstrated that cigarette smoke (CS) activates reactive oxygen species (ROS)-sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling resulting in induction of lung inflammation. Eicosapentaenoic acid (EPA), a major type of omega-3 polyunsaturated fatty acid, is present in significant amounts in marine-based fish and fish oil. EPA has been shown to possess antioxidant and anti-inflammatory properties in vitro and in vivo. However, whether EPA has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we show that subchronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration (total cell count in bronchoalveolar lavage fluid (BALF), 11.0-fold increase), increased lung vascular permeability (protein level in BALF, 3.1-fold increase), elevated levels of chemokines (11.4–38.2-fold increase) and malondialdehyde (an oxidative stress biomarker; 2.0-fold increase) in the lungs, as well as lung inflammation; all of these CS-induced events were suppressed by daily supplementation with EPA. Using human bronchial epithelial cells, we further show that CS extract (CSE) sequentially activated NADPH oxidase (NADPH oxidase activity, 1.9-fold increase), increased intracellular levels of ROS (3.0-fold increase), activated both MAPKs and NF-κB, and induced interleukin-8 (IL-8; 8.2-fold increase); all these CSE-induced events were inhibited by pretreatment with EPA. Our findings suggest a novel role for EPA in alleviating the oxidative stress and lung inflammation induced by subchronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro via its antioxidant function and by inhibiting MAPKs/NF-κB signaling. PMID:25452730

  17. Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

  18. Vitamin C Prevents Cigarette Smoke-Induced Leukocyte Aggregation and Adhesion to Endothelium in vivo

    NASA Astrophysics Data System (ADS)

    Lehr, Hans-Anton; Frei, Balz; Arfors, Karl-E.

    1994-08-01

    A common feature of cigarette-smoke (CS)-associated diseases such as atherosclerosis and pulmonary emphysema is the activation, aggregation, and adhesion of leukocytes to micro- and macrovascular endothelium. A previous study, using a skinfold chamber model for intravital fluorescence microscopy in awake hamsters, has shown that exposure of hamsters to the smoke generated by one research cigarette elicits the adhesion of fluorescently labeled leukocytes to the endothelium of arterioles and small venules. By the combined use of intravital microscopy and scanning electron microscopy, we now demonstrate in the same animal model that (i) CS-induced leukocyte adhesion is not confined to the microcirculation, but that leukocytes also adhere singly and in clusters to the aortic endothelium; (ii) CS induces the formation in the bloodstream of aggregates between leukocytes and platelets; and (iii) CS-induced leukocyte adhesion to micro- and macrovascular endothelium and leukocyte-platelet aggregate formation are almost entirely prevented by dietary or intravenous pretreatment with the water-soluble antioxidant vitamin C (venules, 21.4 ± 11.0 vs. 149.6 ± 38.7 leukocytes per mm^2, P < 0.01; arterioles, 8.5 ± 4.2 vs. 54.3 ± 21.6 leukocytes per mm^2, P < 0.01; aortas, 0.8 ± 0.4 vs. 12.4 ± 5.6 leukocytes per mm^2, P < 0.01; means ± SD of n = 7 animals, 15 min after CS exposure). No inhibitory effect was observed by pretreatment of the animals with the lipid-soluble antioxidants vitamin E or probucol. The protective effects of vitamin C on CS-induced leukocyte adhesion and aggregation were seen at vitamin C plasma levels (55.6 ± 22.2 μM, n = 7) that can easily be reached in humans by dietary means or supplementation, suggesting that vitamin C effectively contributes to protection from CS-associated cardiovascular and pulmonary diseases in humans.

  19. Cigarette smoke-induced oxidative stress in skeletal muscles of mice.

    PubMed

    Barreiro, Esther; del Puerto-Nevado, Laura; Puig-Vilanova, Ester; Pérez-Rial, Sandra; Sánchez, Francisco; Martínez-Galán, Lourdes; Rivera, Stephanie; Gea, Joaquim; González-Mangado, Nicolás; Peces-Barba, Germán

    2012-06-15

    Cigarette smoke (CS)-induced oxidative stress may cause muscle alterations in chronic conditions such as chronic obstructive pulmonary disease (COPD). We sought to explore in AKR/J mice exposed to CS for 6 months and in control animals, levels of protein oxidation, oxidized proteins (immunoblotting, proteomics) and antioxidant mechanisms in both respiratory and limb muscles, body weight modifications, systemic inflammation, and lung structure. Compared to control mice, CS-exposed animals exhibited a reduction in body weight gain at 3 months and thereafter, showed lung emphysema, and exhibited increased oxidative stress levels in their diaphragms and gastrocnemius at 6 months. Proteins involved in glycolysis, ATP production and distribution, carbon dioxide hydration, and muscle contraction were carbonylated in respiratory and limb muscles. Blood tumor necrosis factor (TNF)-alpha levels were significantly greater in CS-exposed mice than in control animals. In AKR/J mice, chronic exposure to CS induces lung emphysema concomitantly with greater oxidative modifications on muscle proteins in both respiratory and limb muscles, and systemic inflammation.

  20. Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes.

    PubMed

    Kanaji, Nobuhiro; Basma, Hesham; Nelson, Amy; Farid, Maha; Sato, Tadashi; Nakanishi, Masanori; Wang, Xingqi; Michalski, Joel; Li, YingJi; Gunji, Yoko; Feghali-Bostwick, Carol; Liu, Xiangde; Rennard, Stephen I

    2014-09-01

    This study assessed the effect of extended exposure to cigarette smoke extract (CSE) on tissue repair functions in lung fibroblasts. Human fetal (HFL-1) and adult lung fibroblasts were exposed to CSE for 14 days. Senescence-associated β-galactosidase (SA β-gal) expression, cell proliferation, and tissue repair functions including chemotaxis and gel contraction were assessed. HFL-1 proliferation was inhibited by CSE and nearly half of the CSE-exposed cells were SA β-gal positive after 14 days exposure, whereas 33% of adult lung fibroblasts were SA β-gal positive in response to 10% CSE exposure. The SA β-gal-positive cells did not proliferate as indicated by bromodeoxyuridine incorporation. In contrast, cells negative for SA β-gal after CSE exposure proliferated faster than cells never exposed to CSE. These nonsenescent cells migrated more and contracted collagen gels more than control cells. CSE exposure stimulated TGF-β1 production, and both inhibition of TGF-β receptor kinase and TGF-β1 siRNA blocked CSE modulation of fibroblast function. Extended exposure to CSE might induce two different fibroblast phenotypes, a senescent and a profibrotic phenotype. The fibroblasts that resist CSE-induced cellular senescence may contribute to the pathogenesis of idiopathic pulmonary fibrosis and could contribute to fibrotic lesions in chronic obstructive pulmonary disease acting through a TGF-β1-mediated pathway. In contrast, the senescent cells may contribute to the pathogenesis of emphysema.

  1. Cigarette smoke-induced mitochondrial fragmentation and dysfunction in human airway smooth muscle

    PubMed Central

    Aravamudan, Bharathi; Kiel, Alexander; Freeman, Michelle; Delmotte, Philippe; Thompson, Michael; Vassallo, Robert; Sieck, Gary C.; Pabelick, Christina M.

    2014-01-01

    The balance between mitochondrial fission and fusion is crucial for mitochondria to perform its normal cellular functions. We hypothesized that cigarette smoke (CS) disrupts this balance and enhances mitochondrial dysfunction in the airway. In nonasthmatic human airway smooth muscle (ASM) cells, CS extract (CSE) induced mitochondrial fragmentation and damages their networked morphology in a concentration-dependent fashion, via increased expression of mitochondrial fission protein dynamin-related protein 1 (Drp1) and decreased fusion protein mitofusin (Mfn) 2. CSE effects on Drp1 vs. Mfn2 and mitochondrial network morphology involved reactive oxygen species (ROS), activation of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), protein kinase C (PKC) and proteasome pathways, as well as transcriptional regulation via factors such as NF-κB and nuclear erythroid 2-related factor 2. Inhibiting Drp1 prevented CSE effects on mitochondrial networks and ROS generation, whereas blocking Mfn2 had the opposite, detrimental effect. In ASM from asmatic patients, mitochondria exhibited substantial morphological defects at baseline and showed increased Drp1 but decreased Mfn2 expression, with exacerbating effects of CSE. Overall, these results highlight the importance of mitochondrial networks and their regulation in the context of cellular changes induced by insults such as inflammation (as in asthma) or CS. Altered mitochondrial fission/fusion proteins have a further potential to influence parameters such as ROS and cell proliferation and apoptosis relevant to airway diseases. PMID:24610934

  2. Cigarette Smoke-Induced Pulmonary Inflammation and Autophagy Are Attenuated in Ephx2-Deficient Mice.

    PubMed

    Li, Yunxiao; Yu, Ganggang; Yuan, Shaopeng; Tan, Chunting; Lian, Puqiao; Fu, Lixia; Hou, Qi; Xu, Bo; Wang, Haoyan

    2016-12-27

    Cigarette smoke (CS) increases the risk of chronic obstructive pulmonary disease (COPD) by causing inflammation, emphysema, and reduced lung function. Additionally, CS can induce autophagy which contributes to COPD. Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) have promising anti-inflammatory properties that may protect the heart and liver by regulating autophagy. For this reason, the effect of decreased soluble epoxide hydrolase (sEH, Ephx2)-mediated EET hydrolysis on inflammation, emphysema, lung function, and autophagy was here studied in CS-induced COPD in vivo. Adult male wild-type (WT) C57BL/6J and Ephx2(-/-) mice were exposed to air or CS for 12 weeks, and lung inflammatory responses, air space enlargement (emphysema), lung function, and autophagy were assessed. Lungs of Ephx2(-/-) mice had a less pronounced inflammatory response and less autophagy with mild distal airspace enlargement accompanied by restored lung function and steady weight gain. These findings support the idea that Ephx2 may hold promise as a therapeutic target for COPD induced by CS, and it may be protective property by inhibiting autophagy.

  3. Angiotensin receptor blockade attenuates cigarette smoke-induced lung injury and rescues lung architecture in mice.

    PubMed

    Podowski, Megan; Calvi, Carla; Metzger, Shana; Misono, Kaori; Poonyagariyagorn, Hataya; Lopez-Mercado, Armando; Ku, Therese; Lauer, Thomas; McGrath-Morrow, Sharon; Berger, Alan; Cheadle, Christopher; Tuder, Rubin; Dietz, Harry C; Mitzner, Wayne; Wise, Robert; Neptune, Enid

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is a prevalent smoking-related disease for which no disease-altering therapies currently exist. As dysregulated TGF-β signaling associates with lung pathology in patients with COPD and in animal models of lung injury induced by chronic exposure to cigarette smoke (CS), we postulated that inhibiting TGF-β signaling would protect against CS-induced lung injury. We first confirmed that TGF-β signaling was induced in the lungs of mice chronically exposed to CS as well as in COPD patient samples. Importantly, key pathological features of smoking-associated lung disease in patients, e.g., alveolar injury with overt emphysema and airway epithelial hyperplasia with fibrosis, accompanied CS-induced alveolar cell apoptosis caused by enhanced TGF-β signaling in CS-exposed mice. Systemic administration of a TGF-β-specific neutralizing antibody normalized TGF-β signaling and alveolar cell death, conferring improved lung architecture and lung mechanics in CS-exposed mice. Use of losartan, an angiotensin receptor type 1 blocker used widely in the clinic and known to antagonize TGF-β signaling, also improved oxidative stress, inflammation, metalloprotease activation and elastin remodeling. These data support our hypothesis that inhibition of TGF-β signaling through angiotensin receptor blockade can attenuate CS-induced lung injury in an established murine model. More importantly, our findings provide a preclinical platform for the development of other TGF-β-targeted therapies for patients with COPD.

  4. Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema

    PubMed Central

    You, Ran; Lu, Wen; Shan, Ming; Berlin, Jacob M; Samuel, Errol LG; Marcano, Daniela C; Sun, Zhengzong; Sikkema, William KA; Yuan, Xiaoyi; Song, Lizhen; Hendrix, Amanda Y; Tour, James M; Corry, David B; Kheradmand, Farrah

    2015-01-01

    Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers. DOI: http://dx.doi.org/10.7554/eLife.09623.001 PMID:26437452

  5. Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin).

    PubMed

    Pini, Alessandro; Boccalini, Giulia; Lucarini, Laura; Catarinicchia, Stefano; Guasti, Daniele; Masini, Emanuela; Bani, Daniele; Nistri, Silvia

    2016-06-01

    Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD), which is characterized by airway remodeling, lung inflammation and fibrosis, emphysema, and respiratory failure. The current therapies can improve COPD management but cannot arrest its progression and reduce mortality. Hence, there is a major interest in identifying molecules susceptible of development into new drugs to prevent or reduce CS-induced lung injury. Serelaxin (RLX), or recombinant human relaxin-2, is a promising candidate because of its anti-inflammatory and antifibrotic properties highlighted in lung disease models. Here, we used a guinea pig model of CS-induced lung inflammation, and remodeling reproducing some of the hallmarks of COPD. Animals exposed chronically to CS (8 weeks) were treated with vehicle or RLX, delivered by osmotic pumps (1 or 10 μg/day) or aerosol (10 μg/ml/day) during CS treatment. Controls were nonsmoking animals. RLX maintained airway compliance to a control-like pattern, likely because of its capability to counteract lung inflammation and bronchial remodeling. In fact, treatment of CS-exposed animals with RLX reduced the inflammatory recruitment of leukocytes, accompanied by a significant reduction of the release of proinflammatory cytokines (tumor necrosis factor α and interleukin-1β). Moreover, RLX was able to counteract the adverse bronchial remodeling and emphysema induced by CS exposure by reducing goblet cell hyperplasia, smooth muscle thickening, and fibrosis. Of note, RLX delivered by aerosol has shown a comparable efficacy to systemic administration in reducing CS-induced lung dysfunction and damage. In conclusion, RLX emerges as a new molecule to counteract CS-induced inflammatory lung diseases.

  6. Protection from cigarette smoke-induced vascular injury by recombinant human relaxin-2 (serelaxin).

    PubMed

    Pini, Alessandro; Boccalini, Giulia; Baccari, Maria Caterina; Becatti, Matteo; Garella, Rachele; Fiorillo, Claudia; Calosi, Laura; Bani, Daniele; Nistri, Silvia

    2016-05-01

    Smoking is regarded as a major risk factor for the development of cardiovascular diseases (CVD). This study investigates whether serelaxin (RLX, recombinant human relaxin-2) endowed with promising therapeutic properties in CVD, can be credited of a protective effect against cigarette smoke (CS)-induced vascular damage and dysfunction. Guinea pigs exposed daily to CS for 8 weeks were treated with vehicle or RLX, delivered by osmotic pumps at daily doses of 1 or 10 μg. Controls were non-smoking animals. Other studies were performed on primary guinea pig aortic endothelial (GPAE) cells, challenged with CS extracts (CSE) in the absence and presence of 100 ng/ml (17 nmol/l) RLX. In aortic specimens from CS-exposed guinea pigs, both the contractile and the relaxant responses to phenylephrine and acetylcholine, respectively, were significantly reduced in amplitude and delayed, in keeping with the observed adverse remodelling of the aortic wall, endothelial injury and endothelial nitric oxide synthase (eNOS) down-regulation. RLX at both doses maintained the aortic contractile and relaxant responses to a control-like pattern and counteracted aortic wall remodelling and endothelial derangement. The experiments with GPAE cells showed that CSE significantly decreased cell viability and eNOS expression and promoted apoptosis by sparkling oxygen free radical-related cytotoxicity, while RLX counterbalanced the adverse effects of CSE. These findings demonstrate that RLX is capable of counteracting CS-mediated vascular damage and dysfunction by reducing oxidative stress, thus adding a tile to the growing mosaic of the beneficial effects of RLX in CVD.

  7. Critical role of CFTR-dependent lipid rafts in cigarette smoke-induced lung epithelial injury

    PubMed Central

    Bodas, Manish; Min, Taehong

    2011-01-01

    Apoptosis of lung epithelial and endothelial cells by exposure to cigarette smoke (CS) severely damages the lung tissue, leading to the pathogenesis of emphysema, but the underlying mechanisms are poorly understood. We have recently established a direct correlation between decreased lipid raft CFTR expression and emphysema progression through increased ceramide accumulation. In the present work, we investigated the role of membrane CFTR in regulating apoptosis and autophagy responses to CS exposure. We report a constitutive and CS-induced increase in the number of TUNEL-positive apoptotic cells in Cftr−/− murine lungs compared with Cftr+/+ murine lungs that also correlated with a concurrent increase in the expression of ceramide, NF-κB, CD95/Fas, lipid raft proteins, and zonula occludens (ZO)-1/2 (P < 0.001). We also verified that stable wild-type CFTR expression in CFBE41o− cells controls constitutively elevated caspase-3/7 activity (−1.6-fold, P < 0.001). Our data suggest that membrane CFTR regulates ceramide-enriched lipid raft signaling platforms required for the induction of Fas-mediated apoptotic signaling. In addition, lack of membrane CFTR also modulates autophagy, as demonstrated by the significant increase in constitutive (P < 0.001) and CSE-induced (P < 0.005) perinuclear accumulation of green fluorescent protein-microtubule-associated protein 1 light chain-3 (LC3) in the absence of membrane CFTR (CFBE41o− cells). The significant constitutive and CS-induced increase (P < 0.05) in p62 and LC3β expression in CFTR-deficient cells and mice corroborates these findings and suggest a defective autophagy response in the absence of membrane CFTR. Our data demonstrate the critical role of membrane-localized CFTR in regulating apoptotic and autophagic responses in CS-induced lung injury that may be involved in the pathogenesis of severe emphysema. PMID:21378025

  8. Critical role of CFTR-dependent lipid rafts in cigarette smoke-induced lung epithelial injury.

    PubMed

    Bodas, Manish; Min, Taehong; Vij, Neeraj

    2011-06-01

    Apoptosis of lung epithelial and endothelial cells by exposure to cigarette smoke (CS) severely damages the lung tissue, leading to the pathogenesis of emphysema, but the underlying mechanisms are poorly understood. We have recently established a direct correlation between decreased lipid raft CFTR expression and emphysema progression through increased ceramide accumulation. In the present work, we investigated the role of membrane CFTR in regulating apoptosis and autophagy responses to CS exposure. We report a constitutive and CS-induced increase in the number of TUNEL-positive apoptotic cells in Cftr(-/-) murine lungs compared with Cftr(+/+) murine lungs that also correlated with a concurrent increase in the expression of ceramide, NF-κB, CD95/Fas, lipid raft proteins, and zonula occludens (ZO)-1/2 (P < 0.001). We also verified that stable wild-type CFTR expression in CFBE41o(-) cells controls constitutively elevated caspase-3/7 activity (-1.6-fold, P < 0.001). Our data suggest that membrane CFTR regulates ceramide-enriched lipid raft signaling platforms required for the induction of Fas-mediated apoptotic signaling. In addition, lack of membrane CFTR also modulates autophagy, as demonstrated by the significant increase in constitutive (P < 0.001) and CSE-induced (P < 0.005) perinuclear accumulation of green fluorescent protein-microtubule-associated protein 1 light chain-3 (LC3) in the absence of membrane CFTR (CFBE41o(-) cells). The significant constitutive and CS-induced increase (P < 0.05) in p62 and LC3β expression in CFTR-deficient cells and mice corroborates these findings and suggest a defective autophagy response in the absence of membrane CFTR. Our data demonstrate the critical role of membrane-localized CFTR in regulating apoptotic and autophagic responses in CS-induced lung injury that may be involved in the pathogenesis of severe emphysema.

  9. TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema.

    PubMed

    An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C; Ifedigbo, Emeka; Washko, George R; Ryter, Stefan W; Choi, Augustine M K

    2012-11-01

    Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.

  10. Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Suzuki, Masaru; Betsuyaku, Tomoko; Ito, Yoko; Nagai, Katsura; Odajima, Nao; Moriyama, Chinatsu; Nasuhara, Yasuyuki; Nishimura, Masaharu

    2009-04-01

    Curcumin, a yellow pigment obtained from turmeric (Curcumina longa), is a dietary polyphenol that has been reported to possess anti-inflammatory and antioxidant properties. The effect of curcumin against the development of pulmonary emphysema in animal models is unknown. The aim of this study was to determine whether curcumin is able to attenuate the development of pulmonary emphysema in mice. Nine-week-old male C57BL/6J mice were treated with intratracheal porcine pancreatic elastase (PPE) or exposed to mainstream cigarette smoke (CS) (60 min/day for 10 consecutive days or 5 days/wk for 12 wk) to induce pulmonary inflammation and emphysema. Curcumin (100 mg/kg) or vehicle was administrated daily by oral gavage 1 h and 24 h before intratracheal PPE treatment and daily thereafter throughout a 21-day period in PPE-exposed mice and 1 h before each CS exposure in CS-exposed mice. As a result, curcumin treatment significantly inhibited PPE-induced increase of neutrophils in bronchoalveolar lavage fluid at 6 h and on day 1 after PPE administration, with an increase in antioxidant gene expression at 6 h and significantly attenuated PPE-induced air space enlargement on day 21. It was also found that curcumin treatment significantly inhibited CS-induced increase of neutrophils and macrophages in bronchoalveolar lavage fluid after 10 consecutive days of CS exposure and significantly attenuated CS-induced air space enlargement after 12 wk of CS exposure. In conclusion, oral curcumin administration attenuated PPE- and CS-induced pulmonary inflammation and emphysema in mice.

  11. Lactosylceramide-accumulation in lipid-rafts mediate aberrant-autophagy, inflammation and apoptosis in cigarette smoke induced emphysema.

    PubMed

    Bodas, Manish; Min, Taehong; Vij, Neeraj

    2015-05-01

    Ceramide-accumulation is known to be involved in the pathogenesis of chronic inflammatory lung diseases including cigarette smoke-induced emphysema (CS-emphysema) but the exact sphingolipid metabolite that initiates emphysema progression remains ambiguous. We evaluated here a novel role for the sphingolipid, lactosylceramide (LacCer), as a potential mechanism for pathogenesis of CS-emphysema. We assessed the expression of LacCer, and LacCer-dependent inflammatory, apoptosis and autophagy responses in lungs of mice exposed to CS, as well as peripheral lung tissues from COPD subjects followed by experimental analysis to verify the role of LacCer in CS-emphysema. We observed significantly elevated LacCer-accumulation in human COPD lungs with increasing severity of emphysema over non-emphysema controls. Moreover, increased expression of defective-autophagy marker, p62, in lung tissues of severe COPD subjects suggest that LacCer induced aberrant-autophagy may contribute to the pathogenesis of CS-emphysema. We verified that CS-extract treatment significantly induces LacCer-accumulation in both bronchial-epithelial cells (BEAS2B) and macrophages (Raw264.7) as a mechanism to initiate aberrant-autophagy (p62-accumulation) and apoptosis that was rescued by pharmacological inhibitor of LacCer-synthase. Further, we corroborated that CS exposure induces LacCer-accumulation in murine lungs that can be controlled by LacCer-synthase inhibitor. We propose LacCer-accumulation as a novel prognosticator of COPD-emphysema severity, and provide evidence on the therapeutic efficacy of LacCer-synthase inhibitor in CS induced COPD-emphysema.

  12. Everything prevents emphysema: are animal models of cigarette smoke-induced chronic obstructive pulmonary disease any use?

    PubMed

    Churg, Andrew; Sin, Don D; Wright, Joanne L

    2011-12-01

    There is a very large number of experimental approaches that prevent cigarette smoke-induced emphysema in laboratory animals, but the few similar treatments that have been tried in humans have had minimal effects, leading to questions of whether animal models of chronic obstructive pulmonary disease (COPD) are of any use in developing treatments for human disease. We review possible reasons for this problem. First, humans usually get treated when they have severe (Global Initiative for Chronic Obstructive Lung Disease III/IV) COPD, but animal models only produce mild (Global Initiative for Chronic Obstructive Lung Disease I/II) disease that never progresses after smoking cessation, and never develops spontaneous exacerbations (i.e., animal models are not models of severe human disease, and probably can't be used to model treatment of severe disease). Second, animal models have concentrated on emphysema and largely ignored small airway remodeling, but small airway remodeling is an equally important cause of airflow obstruction. In addition, small airway remodeling and emphysema are independent responses to smoke, and some experimental animal treatments prevent both lesions, but many do not. Third, animal models are typically Day 1 of smoke exposure "prevention" models, but humans are always treated well along in the course of their disease; thus, any human treatment will be an intervention, and not a prevention. We propose that animal models should examine both emphysema and small airway remodeling, and that experiments should include a relatively late intervention arm. This approach, combined with the realization that human COPD probably needs early rather than late treatment, may make development of treatments based on animal models more relevant.

  13. Erythromycin ameliorates cigarette-smoke-induced emphysema and inflammation in rats.

    PubMed

    Zhou, Yan; Tan, Xianshu; Kuang, Wenjuan; Liu, Litao; Wan, Lihong

    2012-06-01

    The exposure to cigarette smoke (CS) is associated with emphysema. In addition to chronic lung inflammation, emphysema is known mainly for the complex pathogenesis associated with imbalance of proteolytic and antiproteolytic activities, oxidative stress, and apoptosis of lung structural cells. Increasing evidence shows that erythromycin, which is a macrolide antibiotic, ameliorates chronic inflammation via mechanisms independent of its antibacterial activity. We hypothesize that erythromycin protects against CS-induced emphysema and inflammation in rats via its anti-inflammation and antiapoptosis action. Sprague-Dawley (SD) rats were administered lipopolysaccharide (LPS) intratracheally solution twice and exposed to the CS, the control rats were administered saline intratracheally and exposed to ambient air for 3 weeks. Then, all the CS rats were distributed randomly into 3 groups and, respectively, treated orally with saline (LPS + CS + saline), Guilongkechuanning capsule (450 mg/kg) (LPS + CS + GLKCN), or erythromycin (100 mg/kg) (LPS + CS + ERY) 0.5 h before CS exposure for 2 weeks. On day 36, the rats were killed. The cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). The middle lobe of the right lung was removed for histology and apoptosis analyses, respectively. Emphysematous lesions and inflammatory cell infiltrations in the CS group were evident by a histologic analysis. Erythromycin protected significantly against the alveolar enlargement levels (P = 0.0017), reduced the pathologic apoptosis (P = 0.0023) related with Bcl-2 (P = 0.0002) and Bax (P = 0.0002), and inhibited the expressions of matrix metalloproteinase (MMP)-9 (P = 0.0019) and TIMP-1 protein (P = 0.04) and the MMP-9/TIMP-1 ratio (P = 0.0002) in the lungs of CS-induced emphysema in rats. The protective effect of erythromycin on CS-induced emphysema and inflammation in rats is associated with a reduction in inflammation, imbalance of MMP-9/TIMP-1, and apoptosis of

  14. Role of recently migrated monocytes in cigarette smoke-induced lung inflammation in different strain of mice.

    PubMed

    Pérez-Rial, Sandra; del Puerto-Nevado, Laura; Terrón-Expósito, Raúl; Girón-Martínez, Álvaro; González-Mangado, Nicolás; Peces-Barba, Germán

    2013-01-01

    This study investigates the role of proinflammatory monocytes recruited from blood circulation and recovered in bronchoalveolar lavage (BAL) fluid in mediating the lung damage in a model of acute cigarette smoke (CS)-induced lung inflammation in two strains of mice with different susceptibility to develop emphysema (susceptible -C57BL/6J and non susceptible -129S2/SvHsd). Exposure to whole-body CS for 3 consecutive research cigarettes in one single day induced acute inflammation in the lung of mice. Analysis of BAL fluid showed more influx of recently migrated monocytes at 72 h after CS-exposition in susceptible compared to non susceptible mice. It correlated with an increase in MMP-12 and TNF-α protein levels in the lung tissue, and with an increment of NF-κB translocation to the nucleus measured by electrophoretic mobility shift assay in C57BL/6J mice. To determine the functional role of these proinflammatory monocytes in mediating CS-induced airway inflammation, alveolar macrophages and blood monocytes were transiently removed by pretreatment with intratracheal and intravenous liposome-encapsulated CL2MDP, given 2 and 4 days prior to CS exposure and their repopulation was studied. Monocytes/macrophages were maximally depleted 48 h after last liposome application and subsequently recently migrated monocytes reappeared in BAL fluid of susceptible mice at 72 h after CS exposure. Recently migrated monocytes influx to the lung correlated with an increase in the MMP-12 protein level in the lung tissue, indicating that the increase in proinflammatory monocytes is associated with a major tissue damaging. Therefore our data confirm that the recruitment of proinflammatory recently migrated monocytes from the blood are responsible for the increase in MMP-12 and has an important role in the pathogenesis of lung disease induced by acute lung inflammation. These results could contribute to understanding the different susceptibility to CS of these strains of mice.

  15. Role of Recently Migrated Monocytes in Cigarette Smoke-Induced Lung Inflammation in Different Strain of Mice

    PubMed Central

    Pérez-Rial, Sandra; del Puerto-Nevado, Laura; Terrón-Expósito, Raúl; Girón-Martínez, Álvaro; González-Mangado, Nicolás; Peces-Barba, Germán

    2013-01-01

    This study investigates the role of proinflammatory monocytes recruited from blood circulation and recovered in bronchoalveolar lavage (BAL) fluid in mediating the lung damage in a model of acute cigarette smoke (CS)-induced lung inflammation in two strains of mice with different susceptibility to develop emphysema (susceptible -C57BL/6J and non susceptible -129S2/SvHsd). Exposure to whole-body CS for 3 consecutive research cigarettes in one single day induced acute inflammation in the lung of mice. Analysis of BAL fluid showed more influx of recently migrated monocytes at 72 h after CS-exposition in susceptible compared to non susceptible mice. It correlated with an increase in MMP-12 and TNF-α protein levels in the lung tissue, and with an increment of NF-κB translocation to the nucleus measured by electrophoretic mobility shift assay in C57BL/6J mice. To determine the functional role of these proinflammatory monocytes in mediating CS-induced airway inflammation, alveolar macrophages and blood monocytes were transiently removed by pretreatment with intratracheal and intravenous liposome-encapsulated CL2MDP, given 2 and 4 days prior to CS exposure and their repopulation was studied. Monocytes/macrophages were maximally depleted 48 h after last liposome application and subsequently recently migrated monocytes reappeared in BAL fluid of susceptible mice at 72 h after CS exposure. Recently migrated monocytes influx to the lung correlated with an increase in the MMP-12 protein level in the lung tissue, indicating that the increase in proinflammatory monocytes is associated with a major tissue damaging. Therefore our data confirm that the recruitment of proinflammatory recently migrated monocytes from the blood are responsible for the increase in MMP-12 and has an important role in the pathogenesis of lung disease induced by acute lung inflammation. These results could contribute to understanding the different susceptibility to CS of these strains of mice. PMID

  16. A low vitamin A status increases the susceptibility to cigarette smoke-induced lung emphysema in C57BL/6J mice.

    PubMed

    van Eijl, S; Mortaz, E; Versluis, C; Nijkamp, F P; Folkerts, G; Bloksma, N

    2011-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Cigarette smoke has been considered a major player in the pathogenesis of COPD. The inflamed airways of COPD patients contain several inflammatory cells. Vitamin A metabolites have been implicated in the repair of lung damage. Exposure to cigarette smoke has been shown to depress levels of retinol in lungs of rats. The purpose of this study was to investigate if a low, but not deficient, vitamin A status potentiated susceptibility to the development of cigarette smoke-induced lung emphysema in mice. Mice were bred that were the offspring's of 3 generations of mice that were fed a purified diet containing low levels of vitamin A and exposed to cigarette smoke for 3 months, every weekday. Then, levels of 9-cis, 13-cis, and all-trans retinoic acid, retinol and retinyl palmitate were measured in plasma, liver and right lung lobe. The left lung lobe was used to assess mean linear intercept (Lm), as a measure of smoke-induced lung damage. Average feed intakes were not different between treatment groups. We show that both retinol and retinyl palmitate levels were dramatically decreased in the storage organs of mice on the low vitamin A diet (retinol 2-fold in both lung and liver, and retinyl palmitate 5- fold in lung) which shows that the depletion was successful. However, this treatment did not result in the development of lung emphysema. However, smoke exposure led to a significant increase in Lm in mice with a low vitamin A status compared to the room air-breathing controls. Lung levels of acid retinoids were similar in all mice, irrespective of diet or smoke exposure. Concluding, a low vitamin A status increases the susceptibility to the development of cigarette smoke-induced lung emphysema, possibly because of decreased anti-oxidant capacity in the lungs due to locally reduced retinol and retinyl palmitate levels. These observations indicate that human populations with a low

  17. The standardized herbal formula, PM014, ameliorated cigarette smoke-induced lung inflammation in a murine model of chronic obstructive pulmonary disease

    PubMed Central

    2013-01-01

    Background In this study, we evaluated the anti-inflammatory effect of PM014 on cigarette smoke induced lung disease in the murine animal model of chronic obstructive pulmonary disease (COPD). Methods Mice were exposed to cigarette smoke (CS) for 2 weeks to induce COPD-like lung inflammation. Two hours prior to cigarette smoke exposure, the treatment group was administered PM014 via an oral injection. To investigate the effects of PM014, we assessed PM014 functions in vivo, including immune cell infiltration, cytokine profiles in bronchoalveolar lavage (BAL) fluid and histopathological changes in the lung. The efficacy of PM014 was compared with that of the recently developed anti-COPD drug, roflumilast. Results PM014 substantially inhibited immune cell infiltration (neutrophils, macrophages, and lymphocytes) into the airway. In addition, IL-6, TNF-α and MCP-1 were decreased in the BAL fluid of PM014-treated mice compared to cigarette smoke stimulated mice. These changes were more prominent than roflumilast treated mice. The expression of PAS-positive cells in the bronchial layer was also significantly reduced in both PM014 and roflumilast treated mice. Conclusions These data suggest that PM014 exerts strong therapeutic effects against CS induced, COPD-like lung inflammation. Therefore, this herbal medicine may represent a novel therapeutic agent for lung inflammation in general, as well as a specific agent for COPD treatment. PMID:24010767

  18. Trachea Epithelium as a “Canary” for Cigarette Smoking-induced Biologic Phenotype of the Small Airway Epithelium*

    PubMed Central

    Turetz, Meredith L.; O’Connor, Timothy P.; Tilley, Ann E.; Strulovici-Barel, Yael; Salit, Jacqueline; Dang, David; Teater, Matthew; Mezey, Jason; Clark, Andrew G.; Crystal, Ronald G.

    2013-01-01

    The initial site of smoking-induced lung disease is the small airway epithelium, which is difficult and time consuming to sample by fiberoptic bronchoscopy. We developed a rapid, office-based procedure to obtain trachea epithelium without conscious sedation from healthy nonsmokers (n=26) and healthy smokers (n=19, 27 ± 15 pack-yr). Gene expression differences (fold-change >1.5, p<0.01, Benjamini-Hochberg correction) were assessed with Affymetrix microarrays. 1,057 probe sets were differentially expressed in healthy smokers vs nonsmokers, representing >500 genes. Trachea gene expression was compared to an independent group of small airway epithelial samples (n=23 healthy nonsmokers, n=19 healthy smokers, 25 ± 12 pack-yr). The trachea epithelium is more sensitive to smoking, responding with 3-fold more differentially-expressed genes than small airway epithelium. The trachea transcriptome paralleled the small airway epithelium, with 156 of 167 (93%) genes that are significantly upand down-regulated by smoking in the small airway epithelium showing similar direction and magnitude of response to smoking in the trachea. Trachea epithelium can be obtained without conscious sedation, representing a less invasive surrogate “canary” for smoking-induced changes in the small airway epithelium. This should prove useful in epidemiologic studies correlating gene expression with clinical outcome in assessing smoking-induced lung disease. PMID:20443905

  19. Mmp1a and Mmp1b are not functional orthologs to human MMP1 in cigarette smoke induced lung disease.

    PubMed

    Carver, Phillip I; Anguiano, Vincent; D'Armiento, Jeanine M; Shiomi, Takayuki

    2015-02-01

    Matrix Metalloproteinase 1 (MMP1, collagenase-1) expression is implicated in a number of diseased states including emphysema and malignant tumors. The cigarette-smoke induced expression of this interstitial collegenase has been studied extensively and its inhibition proposed as a novel therapeutic treatment for tobacco related diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. However, a limitation in MMP1 research is the inability to take advantage of natural in vivo studies as most research has been performed in vitro or via animal models expressing human forms of the gene due to the lack of a rodent ortholog of MMP1. The present study examines the function of two possible mouse orthologs of human MMP1 known as Mmp1a and Mmp1b. Using genomic sequence analysis and expression analysis of these enzymes, the data demonstrate that neither MMP1a nor MMP1b behave in the same manner as human MMP1 in the presence of cigarette smoke. These findings establish that the two commonly proposed orthologs of MMP1, Mmp1a and Mmp1b, provide substantial limitations for use in examining MMP1 induced lung disease in mouse models of cigarette smoke emphysema.

  20. MAP3K19 Is Overexpressed in COPD and Is a Central Mediator of Cigarette Smoke-Induced Pulmonary Inflammation and Lower Airway Destruction

    PubMed Central

    Franz-Bacon, Karin; Ludka, John; DiTirro, Danielle N.; Ly, Tai Wei; Bacon, Kevin B.

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and lung inflammation resulting in a progressive decline in lung function whose principle cause is cigarette smoke. MAP3K19 is a novel kinase expressed predominantly by alveolar and interstitial macrophages and bronchial epithelial cells in the lung. We found that MAP3K19 mRNA was overexpressed in a limited sampling of lung tissue from COPD patients, and a closer examination found it to be overexpressed in bronchoalveolar macrophages from COPD patients, as well as the bronchial epithelium and inflammatory cells in the lamina propria. We further found MAP3K19 to be induced in various cell lines upon environmental stress, such as cigarette smoke, oxidative and osmotic stress. Exogenous expression of MAP3K19 in cells caused an upregulation of transcriptionally active NF-κB, and secretion of the chemokines CXCL-8, CCL-20 and CCL-7. Inhibition of MAP3K19 activity by siRNA or small molecular weight inhibitors caused a decrease in cigarette smoke-induced inflammation in various murine models, which included a decrease in pulmonary neutrophilia and KC levels. In a chronic cigarette smoke model, inhibition of MAP3K19 significantly attenuated emphysematous changes in airway parenchyma. Finally, in a viral exacerbation model, mice exposed to cigarette smoke and influenza A virus showed a decrease in pulmonary neutrophilia, pro-inflammatory cytokines and viral load upon inhibition of MAP3K19. Collectively, these results suggest that inhibition of MAP3K19 may represent a novel strategy to target COPD that promises to have a potential therapeutic benefit for patients. PMID:27935962

  1. MAP3K19 Is Overexpressed in COPD and Is a Central Mediator of Cigarette Smoke-Induced Pulmonary Inflammation and Lower Airway Destruction.

    PubMed

    Boehme, Stefen A; Franz-Bacon, Karin; Ludka, John; DiTirro, Danielle N; Ly, Tai Wei; Bacon, Kevin B

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and lung inflammation resulting in a progressive decline in lung function whose principle cause is cigarette smoke. MAP3K19 is a novel kinase expressed predominantly by alveolar and interstitial macrophages and bronchial epithelial cells in the lung. We found that MAP3K19 mRNA was overexpressed in a limited sampling of lung tissue from COPD patients, and a closer examination found it to be overexpressed in bronchoalveolar macrophages from COPD patients, as well as the bronchial epithelium and inflammatory cells in the lamina propria. We further found MAP3K19 to be induced in various cell lines upon environmental stress, such as cigarette smoke, oxidative and osmotic stress. Exogenous expression of MAP3K19 in cells caused an upregulation of transcriptionally active NF-κB, and secretion of the chemokines CXCL-8, CCL-20 and CCL-7. Inhibition of MAP3K19 activity by siRNA or small molecular weight inhibitors caused a decrease in cigarette smoke-induced inflammation in various murine models, which included a decrease in pulmonary neutrophilia and KC levels. In a chronic cigarette smoke model, inhibition of MAP3K19 significantly attenuated emphysematous changes in airway parenchyma. Finally, in a viral exacerbation model, mice exposed to cigarette smoke and influenza A virus showed a decrease in pulmonary neutrophilia, pro-inflammatory cytokines and viral load upon inhibition of MAP3K19. Collectively, these results suggest that inhibition of MAP3K19 may represent a novel strategy to target COPD that promises to have a potential therapeutic benefit for patients.

  2. Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette- smoke-induced lung inflammation in mice

    PubMed Central

    Bozinovski, Steven; Seow, Huei Jiunn; Chan, Sheau Pyng Jamie; Anthony, Desiree; McQualter, Jonathan; Hansen, Michelle; Jenkins, Brendan J.; Anderson, Gary P.

    2015-01-01

    Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). Interleukin-17A (IL-17A) is a pivotal cytokine that regulates lung immunity and inflammation. The aim of the present study was to investigate how IL-17A regulates CS-induced lung inflammation in vivo. IL-17A knockout (KO) mice and neutralization of IL-17A in wild-type (WT) mice reduced macrophage and neutrophil recruitment and chemokine (C-C motif) ligand 2 (CCL2), CCL3 and matrix metalloproteinase (MMP)-12 mRNA expression in response to acute CS exposure. IL-17A expression was increased in non-obese diabetic (NOD) severe combined immunodeficiency SCID) mice with non-functional B- and T-cells over a 4-week CS exposure period, where macrophages accumulated to the same extent as in WT mice. Gene expression analysis by QPCR (quantitative real-time PCR) of isolated immune cell subsets detected increased levels of IL-17A transcript in macrophages, neutrophils and NK/NKT cells in the lungs of CS-exposed mice. In order to further explore the relative contribution of innate immune cellular sources, intracellular IL-17A staining was performed. In the present study, we demonstrate that CS exposure primes natural killer (NK), natural killer T (NKT) and γδ T-cells to produce more IL-17A protein and CS alone increased the frequency of IL17+ γδ T-cells in the lung, whereas IL-17A protein was not detected in macrophages and neutrophils. Our data suggest that activation of innate cellular sources of IL-17A is an essential mediator of macrophage accumulation in CS-exposed lungs. Targeting non-conventional T-cell sources of IL-17A may offer an alternative strategy to reduce pathogenic macrophages in COPD. PMID:26201093

  3. Protection of coronary endothelial cells from cigarette smoke-induced oxidative stress by a new Mn(II)-containing polyamine-polycarboxilate scavenger of superoxide anion.

    PubMed

    Becatti, Matteo; Boccalini, Giulia; Pini, Alessandro; Fiorillo, Claudia; Bencini, Andrea; Bani, Daniele; Nistri, Silvia

    2015-12-01

    Oxidative stress plays a major role in cardiovascular injury and dysfunction induced by cigarette smoke. Smoke-borne pro-oxidants impair endothelial function and predispose to thrombosis, inflammation and atherosclerosis. This in vitro study evaluates whether Mn(II)(4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate).2H2O (Mn(II)(Me2DO2A)), a polyamine-polycarboxilate, Mn(II)-containing O2(-) scavenger, has a direct protective action on guinea pig coronary endothelial (GPCE) cells exposed to cigarette smoke extracts (CSE). Mn(II)(Me2DO2A) (1-10μmol/l) was added to the culture medium together with CSE and maintained for 4h. In parallel experiments, the inactive congener Zn(II)(Me2DO2A), in which Zn(II) replaced the functional Mn(II) center in the same organic scaffold, was used as negative control. Mn(II)(Me2DO2A), mostly at the higher doses (5 and 10μmol/l), significantly increased GPCE cell viability (trypan blue assay), improved mitochondrial activity (MTT test, mitochondrial membrane potential Δψ), reduced cellular apoptosis (mPTP, caspase-3 activity, TUNEL assay), decreased intracellular ROS levels (H2DCFDA), lipoperoxidation (BODIPY 581/591) and decreased protein nitrosylation. Of note, Zn(II)(Me2DO2A) did not preserve cell viability. These findings suggest that Mn(II)(Me2DO2A) is a promising O2(-) scavenging compound able to protect from cigarette smoke-induced oxidative cell injury. In perspective, should its efficacy be confirmed in future in vivo studies, this molecule might represent a therapeutic or preventive drug to counteract cigarette smoke toxicity.

  4. Inhibitory effect of Chinese green tea on cigarette smoke-induced up-regulation of airway neutrophil elastase and matrix metalloproteinase-12 via antioxidant activity.

    PubMed

    Chan, Ka Ho; Chan, Stanley Chi Hang; Yeung, Sze Chun; Man, Ricky Ying Keung; Ip, Mary Sau Man; Mak, Judith Choi Wo

    2012-09-01

    Our recent study has indicated that Chinese green tea (Lung Chen), in which epigallocatechin-3-gallate (EGCG) accounts for 60% of catechins, protected cigarette smoke-induced lung injury. We now hypothesized that Lung Chen tea may also have potential effect on lung oxidative stress and proteases/anti-proteases in a smoking rat model. Sprague-Dawley rats were exposed to either sham air (SA) or 4% cigarette smoke (CS) plus 2% Lung Chen tea or water by oral gavage. Serine proteases, matrix metalloproteinases (MMPs) and their respective endogenous inhibitors were determined in bronchoalveolar lavage (BAL) and lung tissues by gelatin/casein zymography and biochemical assays. Green tea consumption significantly decreased CS-induced elevation of lung lipid peroxidation marker, malondialdehyde (MDA), and CS-induced up-regulation of neutrophil elastase (NE) concentration and activity along with that of α(1)-antitrypsin (α(1)-AT) and secretory leukoproteinase inhibitor (SLPI) in BAL and lung. In parallel, significant elevation of MMP-12 activity was found in BAL and lung of the CS-exposed group, which returned to the levels of SA-exposed group after green tea consumption but not CS-induced reduction of tissue inhibitor of metalloproteinase (TIMP)-1 activity, which was not reversed by green tea consumption. Taken together, our data supported the presence of local oxidative stress and protease/anti-protease imbalance in the airways after CS exposure, which might be alleviated by green tea consumption through its biological antioxidant activity.

  5. Cigarette smoke-induced damage-associated molecular pattern release from necrotic neutrophils triggers proinflammatory mediator release.

    PubMed

    Heijink, Irene H; Pouwels, Simon D; Leijendekker, Carin; de Bruin, Harold G; Zijlstra, G Jan; van der Vaart, Hester; ten Hacken, Nick H T; van Oosterhout, Antoon J M; Nawijn, Martijn C; van der Toorn, Marco

    2015-05-01

    Cigarette smoking, the major causative factor for the development of chronic obstructive pulmonary disease, is associated with neutrophilic airway inflammation. Cigarette smoke (CS) exposure can induce a switch from apoptotic to necrotic cell death in airway epithelium. Therefore, we hypothesized that CS promotes neutrophil necrosis with subsequent release of damage-associated molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), alarming the innate immune system. We studied the effect of smoking two cigarettes on sputum neutrophils in healthy individuals and of 5-day CS or air exposure on neutrophil counts, myeloperoxidase, and HMGB1 levels in bronchoalveolar lavage fluid of BALB/c mice. In human peripheral blood neutrophils, mitochondrial membrane potential, apoptosis/necrosis markers, caspase activity, and DAMP release were studied after CS exposure. Finally, we assessed the effect of neutrophil-derived supernatants on the release of chemoattractant CXCL8 in normal human bronchial epithelial cells. Cigarette smoking caused a significant decrease in sputum neutrophil numbers after 3 hours. In mice, neutrophil counts were significantly increased 16 hours after repeated CS exposure but reduced 2 hours after an additional exposure. In vitro, CS induced necrotic neutrophil cell death, as indicated by mitochondrial dysfunction, inhibition of apoptosis, and DAMP release. Supernatants from CS-treated neutrophils significantly increased the release of CXCL8 in normal human bronchial epithelial cells. Together, these observations show, for the first time, that CS exposure induces neutrophil necrosis, leading to DAMP release, which may amplify CS-induced airway inflammation by promoting airway epithelial proinflammatory responses.

  6. Cigarette smoke-induced disruption of bronchial epithelial tight junctions is prevented by transforming growth factor-β.

    PubMed

    Schamberger, Andrea C; Mise, Nikica; Jia, Jie; Genoyer, Emmanuelle; Yildirim, Ali Ö; Meiners, Silke; Eickelberg, Oliver

    2014-06-01

    The airway epithelium constitutes an essential immunological and cytoprotective barrier to inhaled insults, such as cigarette smoke, environmental particles, or viruses. Although bronchial epithelial integrity is crucial for airway homeostasis, defective epithelial barrier function contributes to chronic obstructive pulmonary disease (COPD). Tight junctions at the apical side of epithelial cell-cell contacts determine epithelial permeability. Cigarette smoke exposure, the major risk factor for COPD, is suggested to impair tight junction integrity; however, detailed mechanisms thereof remain elusive. We investigated whether cigarette smoke extract (CSE) and transforming growth factor (TGF)-β1 affected tight junction integrity. Exposure of human bronchial epithelial cells (16HBE14o(-)) and differentiated primary human bronchial epithelial cells (pHBECs) to CSE significantly disrupted tight junction integrity and barrier function. Specifically, CSE decreased transepithelial electrical resistance (TEER) and tight junction-associated protein levels. Zonula occludens (ZO)-1 and ZO-2 protein levels were significantly reduced and dislocated from the cell membrane, as observed by fractionation and immunofluorescence analysis. These findings were reproduced in isolated bronchi exposed to CSE ex vivo, as detected by real-time quantitative reverse-transcriptase PCR and immunohistochemistry. Combined treatment of 16HBE14o(-) cells or pHBECs with CSE and TGF-β1 restored ZO-1 and ZO-2 levels. TGF-β1 cotreatment restored membrane localization of ZO-1 and ZO-2 protein and prevented CSE-mediated TEER decrease. In conclusion, CSE led to the disruption of tight junctions of human bronchial epithelial cells, and TGF-β1 counteracted this CSE-induced effect. Thus, TGF-β1 may serve as a protective factor for bronchial epithelial cell homeostasis in diseases such as COPD.

  7. A potential role for estrogen in cigarette smoke-induced microRNA alterations and lung cancer

    PubMed Central

    Cohen, Amit; Smith, Yoav

    2016-01-01

    Alteration in the expression of microRNAs (miRNAs) is associated with oncogenesis and cancer progression. In this review we aim to suggest that elevated levels of estrogens and their metabolites inside the lungs as a result of cigarette smoke exposure can cause widespread repression of miRNA and contribute to lung tumor development. Anti-estrogenic compounds, such as the components of cruciferous vegetables, can attenuate this effect and potentially reduce the risk of lung cancer (LC) among smokers. PMID:27413713

  8. Protective effect of honey against cigarette smoke induced-impaired sexual behavior and fertility of male rats.

    PubMed

    Mohamed, Mahaneem; Sulaiman, Siti Amrah; Sirajudeen, Kuttulebbai Nainamohamed Salam

    2013-04-01

    Cigarette smoking is associated with sexual dysfunction and impaired fertility in males. The aim of this study was to determine the potential protective effect of honey against the toxic effect of cigarette smoke (CS) on sexual behavior and fertility of male rats. Thirty-two adult Sprague-Dawley rats were randomly divided into four groups (8 rats/group) as control, honey (H), CS and H plus CS (H + CS) groups. Rats in control and CS groups received oral administration of distilled water daily while rats in H and H + CS groups received honey (1.2 g/kg body weight/day) by oral gavage. Rats in CS and H + CS groups were also exposed to CS for 8 min 3 times/day. From 10 to 13 weeks of treatment, each male rat was cohabited with 3 untreated female rats for sexual behavioral and reproductive performance studies. Honey significantly increased the percentages of rats achieving intromission and ejaculation as well as increased mating and fertility indexes of male rats exposed to CS. Thus, honey has a protective effect against CS-induced impaired sexual behavior and fertility in male rats.

  9. Prostacyclin reverses the cigarette smoke-induced decrease in pulmonary Frizzled 9 expression through miR-31

    PubMed Central

    Tennis, M. A.; New, M. L.; McArthur, D. G.; Merrick, D. T.; Dwyer-Nield, L. D.; Keith, R. L.

    2016-01-01

    Half of lung cancers are diagnosed in former smokers, leading to a significant treatment burden in this population. Chemoprevention in former smokers using the prostacyclin analogue iloprost reduces endobronchial dysplasia, a premalignant lung lesion. Iloprost requires the presence of the WNT receptor Frizzled 9 (Fzd9) for inhibition of transformed growth in vitro. To investigate the relationship between iloprost, cigarette smoke, and Fzd9 expression, we used human samples, mouse models, and in vitro studies. Fzd9 expression was low in human lung tumors and in progressive dysplasias. In mouse models and in vitro studies, tobacco smoke carcinogens reduced expression of Fzd9 while prostacyclin maintained or increased expression. Expression of miR-31 repressed Fzd9 expression, which was abrogated by prostacyclin. We propose a model where cigarette smoke exposure increases miR-31 expression, which leads to decreased Fzd9 expression and prevents response to iloprost. When smoke is removed miR-31 is reduced, prostacyclin can increase Fzd9 expression, and progression of dysplasia is inhibited. Fzd9 and miR-31 are candidate biomarkers for precision application of iloprost and monitoring of treatment progress. As we continue to investigate the mechanisms of prostacyclin chemoprevention and identify biomarkers for its use, we will facilitate clinical trials and speed implementation of this valuable prevention approach. PMID:27339092

  10. NADPH oxidase (NOX) 1 mediates cigarette smoke-induced superoxide generation in rat vascular smooth muscle cells.

    PubMed

    Chang, Kyung-Hwa; Park, Jung-Min; Lee, Chang Hoon; Kim, Bumseok; Choi, Kyung-Chul; Choi, Seong-Jin; Lee, Kyuhong; Lee, Moo-Yeol

    2017-02-01

    Smoking is a well-established risk factor for cardiovascular diseases. Oxidative stress is one of the common etiological factors, and NADPH oxidase (NOX) has been suggested as a potential mediator of oxidative stress. In this study, cigarette smoke (CS)-induced superoxide production was characterized in vascular smooth muscle cells (VSMC). CS was prepared in forms of cigarette smoke extract (CSE) and total particulate matter (TPM). Several molecular probes for reactive oxygen species were trialed, and dihydroethidium (DHE) and WST-1 were chosen for superoxide detection considering the autofluorescence, light absorbance, and peroxidase inhibitory activity of CS. Both CSE and TPM generated superoxide in a VSMC culture system by stimulating cells to produce superoxide and by directly producing superoxide in the aqueous solution. NOX, specifically NOX1 was found to be an important cellular source of superoxide through experiments with the NOX inhibitors diphenyleneiodonium (DPI) and VAS2870 as well as isoform-specific NOX knockdown. NOX inhibitors and the superoxide dismutase mimetic TEMPOL reduced the cytotoxicity of CSE, thus suggesting the contribution of NOX1-derived superoxide to cytotoxicity. Since NOX1 is known to mediate diverse pathological processes in the vascular system, NOX1 may be a critical effector of cardiovascular toxicity caused by smoking.

  11. Wood smoke enhances cigarette smoke-induced inflammation by inducing the aryl hydrocarbon receptor repressor in airway epithelial cells.

    PubMed

    Awji, Elias G; Chand, Hitendra; Bruse, Shannon; Smith, Kevin R; Colby, Jennifer K; Mebratu, Yohannes; Levy, Bruce D; Tesfaigzi, Yohannes

    2015-03-01

    Our previous studies showed that cigarette smokers who are exposed to wood smoke (WS) are at an increased risk for chronic bronchitis and reduced lung function. The present study was undertaken to determine the mechanisms for WS-induced adverse effects. We studied the effect of WS exposure using four cohorts of mice. C57Bl/6 mice were exposed for 4 or 12 weeks to filtered air, to 10 mg/m(3) WS for 2 h/d, to 250 mg/m(3) cigarette smoke (CS) for 6 h/d, or to CS followed by WS (CW). Inflammation was absent in the filtered air and WS groups, but enhanced by twofold in the bronchoalveolar lavage of the CW compared with CS group as measured by neutrophil numbers and levels of the neutrophil chemoattractant, keratinocyte-derived chemokine. The levels of the anti-inflammatory lipoxin, lipoxin A4, were reduced by threefold along with cyclo-oxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 in airway epithelial cells and PGE2 levels in the bronchoalveolar lavage of CW compared with CS mice. We replicated, in primary human airway epithelial cells, the changes observed in mice. Immunoprecipitations showed that WS blocked the interaction of aryl hydrocarbon receptor (AHR) with AHR nuclear transporter to reduce expression of COX-2 and mPGES-1 by increasing expression of AHR repressor (AHRR). Collectively, these studies show that exposure to low concentrations of WS enhanced CS-induced inflammation by inducing AHRR expression to suppress AHR, COX-2, and mPGES-1 expression, and levels of PGE2 and lipoxin A4. Therefore, AHRR is a potential therapeutic target for WS-associated exacerbations of CS-induced inflammation.

  12. Cigarette smoke-induced lung inflammation in COPD mediated via LTB4/BLT1/SOCS1 pathway

    PubMed Central

    Dong, Ran; Xie, Liang; Zhao, Kaishun; Zhang, Qiurui; Zhou, Min; He, Ping

    2016-01-01

    Background Evidence suggests that suppressor of cytokine signaling 1 (SOCS1) is crucial for the negative regulation of inflammation. We investigated the relationship between smoking, SOCS1, and leukotriene B4 (LTB4) in vitro and in clinical samples of COPD; besides which we detected the impact of LTB4 receptor 1 (BLT1) antagonist on inflammation. Methods SOCS1 expression in bronchial mucosa was determined by immunohistochemistry and real-time polymerase chain reaction. We also detect SOCS1 and BLT1 expression in alveolar macrophages from bronchoalveolar lavage fluid (BALF) by real time-PCR, in addition to measuring the level of cytokines in BALF using enzyme-linked immunosorbent assay. In vitro, we investigated the expression of SOCS1 in cigarette smoke extract-induced mouse macrophage cell line RAW264.7 by real-time polymerase chain reaction and Western blot, and detected the level of cytokines in the supernatant by enzyme-linked immunosorbent assay. Then, we investigated the effects of BLT1 antagonist U-75302 on SOCS1 expression in these cells. Results We obtained endobronchial biopsies (15 COPD patients and 12 non-COPD control subjects) and BALF (20 COPD patients and 20 non-COPD control subjects), and our results showed that SOCS1 expression significantly decreased in lung tissues from COPD patients. Inflammatory cytokines in BALF were higher in COPD and these inflammatory cytokines negatively correlate with SOCS1 levels. Further, the BLT1 antagonist restored SOCS1 expression and in turn inhibited inflammatory cytokine secretion in vitro. Conclusion Long-term cigarette smoke exposure induced SOCS1 degradation and LTB4 accumulation, which was associated with emphysema and inflammation. A BLT1 antagonist might be a potential therapeutic candidate for the treatment of COPD. PMID:26730186

  13. The aryl hydrocarbon receptor suppresses cigarette-smoke-induced oxidative stress in association with dioxin response element (DRE)-independent regulation of sulfiredoxin 1.

    PubMed

    Sarill, Miles; Zago, Michela; Sheridan, Jared A; Nair, Parameswaran; Matthews, Jason; Gomez, Alvin; Roussel, Lucie; Rousseau, Simon; Hamid, Qutayba; Eidelman, David H; Baglole, Carolyn J

    2015-12-01

    The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed receptor/transcription factor that mediates toxicological responses of environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Emerging evidence indicates that the AhR suppresses apoptosis and proliferation independent of exogenous ligands, including suppression of apoptosis by cigarette smoke, a key risk factor for chronic obstructive pulmonary disease (COPD). As cigarette smoke is a potent inducer of oxidative stress, a feature that may contribute to the development of COPD, we hypothesized that the AhR prevents smoke-induced apoptosis by regulating oxidative stress. Utilizing primary lung fibroblasts derived from AhR(+/+) and AhR(-/-) mice as well as A549 human lung adenocarcinoma cells deficient in AhR expression (A549-AhR(ko)), we first show that AhR(-/-) fibroblasts and A549-AhR(ko) epithelial cells have a significant increase in cigarette smoke extract (CSE)-induced oxidative stress compared to wild type. CSE induced a significant increase in the mRNA expression of key antioxidant genes, including Nqo1 and Srxn1, predominantly in AhR(+/+) fibroblasts, with significantly less induction in AhR(-/-) cells. The induction of Srxn1, but not Nqo1, was independent of dioxin-response element (DRE) binding as AhR(DBD/DBD) lung fibroblasts, which express an AhR incapable of binding the DRE, increased Srxn1 to a degree similar to wild-type cells in response to CSE. There was no difference in Nrf2 expression or activation based on AhR expression. Lung fibroblasts derived from COPD subjects have significantly less AhR protein expression compared with both never-smokers (Normal) and smokers (At Risk). Consequently, COPD-derived fibroblasts were less robust in their induction of both Nqo1 and Srxn1 mRNA after exposure to CSE, which also failed to activate the AhR in the COPD fibroblasts. Taken together, these results support a new role for the AhR in regulating antioxidant defense in lung

  14. Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

    PubMed Central

    Jorgensen, Ellen; Stinson, Andy; Shan, Lin; Yang, Jin; Gietl, Diana; Albino, Anthony P

    2008-01-01

    Background Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke), a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS) impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER) functioning, our data highlighted a defensive role for the unfolded protein response (UPR) program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer. Methods Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry. Results We show that: 1) CS induces ER stress and activates components of the UPR; 2) reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3) CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4) several major UPR regulators are increased either in expression (i.e., BiP and eIF2α) or phosphorylation (i.e., phospho-eIF2α) in a majority of human lung cancers. Conclusion These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have diagnostic and

  15. Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema.

    PubMed

    Voss, Meike; Wolf, Lisa; Kamyschnikow, Andreas; Wonnenberg, Bodo; Honecker, Anja; Herr, Christian; Lepper, Philipp M; Wegmann, Michael; Menger, Michael D; Bals, Robert; Beisswenger, Christoph

    2015-07-15

    Smoking is the main risk factor for the development of the chronic obstructive pulmonary disease (COPD) in Western countries. Recent studies suggest that IL-17A and Th17 cells play a role in the pathogenesis of COPD. We used a murine model of chronic cigarette smoke (CS) exposure to explore the contribution of IL-17A to CS-induced lung damage and loss of pulmonary function. Histology and morphometry showed that IL-17A deficiency spontaneously resulted in a loss of lung structure under basal conditions. Even though inflammatory markers [IL-1β and granulocyte colony-stimulating factor (G-CSF)] were decreased in IL-17A-deficient mice (IL-17A(-/-)) exposed to CS compared with wild-type (WT) mice, IL-17A(-/-) mice were per se not protected from CS-induced emphysematous disease. Assessment of pulmonary function showed that IL-17A(-/-) mice were partially protected from CS-induced changes in total lung capacity. However, the respiratory elastance decreased and respiratory compliance increased in IL-17A(-/-) mice after exposure to CS. Morphometry revealed destruction of lung tissue in CS-exposed IL-17A(-/-) mice similar to WT mice. The expression of elastin was decreased in air-exposed IL-17A(-/-) mice and in CS-exposed WT and IL-17A(-/-) mice. Thus, in the present model of sterile CS-exposure, IL-17A contributes to normal lung homeostasis and does not mediate CS-induced loss of lung structure and pulmonary function.

  16. Cigarette smoke-induced chronic obstructive pulmonary disease is attenuated by CCL20-blocker: a rat model

    PubMed Central

    Sun, Desheng; Ouyang, Yao; Gu, Yanhui; Liu, Xiansheng

    2016-01-01

    Aim To evaluate whether the effect of dendritic cells (DCs) on chronic obstructive pulmonary disease (COPD) can be relieved by blocking CCL20. Methods 30 Wistar rats were randomly divided into three groups: control, COPD, and COPD treated with CCL20 monoclonal antibody. In the latter two groups, COPD was induced by four-week cigarette smoke exposure and trachea injection of lipopolysaccharide solution on two occasions. CCL20 monoclonal antibody was injected intraperitoneally on the first day. All animals were sacrificed on the 29th day. Pathomorphology of the lung and bronchiole was analyzed using hematoxylin and eosin staining. The CCR6 content in the bronchoalveolar lavage fluid was detected using ELISA. DC distribution in the lung was examined by immunohistochemistry for OX62. Results COPD rat models showed pathological alterations similar to those in COPD patients. DCs, CCR6, and the severity of emphysema were significantly increased in the COPD group than in controls (all P values <0.001), and they were significantly reduced after anti-CCL20 treatment compared with the COPD group (all P values <0.05). Conclusion The interaction between CCR6 and its ligand CCL20 promotes the effect of DCs in the COPD pathogenesis, which can be reduced by blocking CCL20. PMID:27586551

  17. Proliferative Activity of Liver Growth Factor is Associated with an Improvement of Cigarette Smoke-Induced Emphysema in Mice

    PubMed Central

    Terrón-Expósito, Raúl; Díaz-Gil, Juan José; González-Mangado, Nicolás; Peces-Barba, Germán

    2014-01-01

    Cigarette smoke (CS)-induced emphysema is a major component of chronic obstructive pulmonary disease (COPD). COPD treatment is based on the administration of bronchodilators and corticosteroids to control symptoms and exacerbations, however, to date, there are no effective therapies to reverse disease progression. Liver growth factor (LGF) is an albumin-bilirubin complex with mitogenic properties, whose therapeutic effects have previously been reported in a model of emphysema and several rodent models of human disease. To approach the therapeutic effect of LGF in a model of previously established emphysema, morphometric and lung function parameters, matrix metalloproteinase (MMP) activity and the expression of several markers, such as VEGF, PCNA, 3NT and Nrf2, were assessed in air-exposed and CS-exposed C57BL/6J male mice with and without intraperitoneal (i.p.) injection of LGF. CS-exposed mice presented a significant enlargement of alveolar spaces, higher alveolar internal area and loss of lung function that correlated with higher MMP activity, higher expression of 3NT and lower expression of VEGF. CS-exposed mice injected with LGF, showed an amelioration of emphysema and improved lung function, which correlated with lower MMP activity and 3NT expression and higher levels of VEGF, PCNA and Nrf2. Taken together, this study suggests that LGF administration ameliorates CS-induced emphysema, highlights the ability of LGF to promote alveolar cell proliferation and may be a promising strategy to revert COPD progression. PMID:25401951

  18. Aldehyde dehydrogenase 3A1 protects airway epithelial cells from cigarette smoke-induced DNA damage and cytotoxicity.

    PubMed

    Jang, Jun-Ho; Bruse, Shannon; Liu, Yushi; Duffy, Veronica; Zhang, Chunyu; Oyamada, Nathaniel; Randell, Scott; Matsumoto, Akiko; Thompson, David C; Lin, Yong; Vasiliou, Vasilis; Tesfaigzi, Yohannes; Nyunoya, Toru

    2014-03-01

    Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels showed the greatest induction in response to CS extract (CSE) exposure of primary human bronchial epithelial cells (HBECs). ALDH3A1 protein accumulation was accompanied by increased ALDH enzymatic activity in CSE-exposed immortalized HBECs. The effects of overexpression or suppression of ALDH3A1 on CSE-induced cytotoxicity and DNA damage (γH2AX) were evaluated in cultured immortalized HBECs. Enforced expression of ALDH3A1 attenuated cytotoxicity and downregulated γH2AX. SiRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity and augmented cytotoxicity in CSE-exposed cells. Our results suggest that the availability of ALDH3A1 is important for cell survival against CSE in HBECs.

  19. Paraoxsonase2 (PON2) and oxidative stress involvement in pomegranate juice protection against cigarette smoke-induced macrophage cholesterol accumulation.

    PubMed

    Rom, Oren; Aviram, Michael

    2016-11-25

    Exposure to cigarette smoke (CS) promotes various stages of atherosclerosis development. Macrophages are the predominant cells in early atherogenesis, and the polyphenolic-rich pomegranate juice (PJ) is known for its protective role against macrophage atherogenicity. The aim of the current study was to examine the atherogenic effects of CS on macrophages, and to evaluate the protective effects of PJ against CS-induced macrophage atherogenicity. Murine J774A.1 macrophages were treated with CS-exposed medium in the absence or presence of PJ. Parameters of lipid peroxidation in CS-exposed medium were measured by the lipid peroxides and thiobarbituric acid reactive substances (TBARS) assays. Atherogenicity of macrophages incubated with increasing concentrations of CS-exposed medium was assessed by cytotoxicity, oxidative stress determined by generation of reactive oxygen species (ROS) using DCFH-DA, activity of the cellular anti-oxidant paraoxonase2 (PON2), macrophage accumulation of cholesterol and triglycerides, as well as through high density lipoprotein (HDL)-mediated cholesterol efflux from the cells. CS exposure resulted in significant and dose-dependent increases in lipid peroxides and TBARS medium levels (up to 3 and 8-fold, respectively). Incubation of macrophages with CS-exposed medium resulted in dose-dependent increases in macrophage damage/injury (up to 6-fold), intracellular ROS levels (up to 31%), PON2 activity (up to 2-fold), and macrophage cholesterol content (up to 24%). The latter might be explained by reduced HDL-mediated cholesterol efflux from CS-exposed macrophages (by 21%). PJ protected macrophages from CS-induced increases in intracellular ROS levels and cholesterol accumulation, as well as the attenuated efflux of cholesterol. These data indicate that CS stimulates macrophage oxidation and activates PON2 as a possible compensatory response to the oxidative burden. CS impairs HDL-mediated cholesterol efflux from macrophages leading to cellular

  20. Cigarette smoke-induced reduction in binding of the salivary translocator protein is not mediated by free radicals.

    PubMed

    Nagler, R; Savulescu, D; Gavish, M

    2016-02-01

    Oral cancer is the most common malignancy of the head and neck and its main inducer is exposure to cigarette smoke (CS) in the presence of saliva. It is commonly accepted that CS contributes to the pathogenesis of oral cancer via reactive free radicals and volatile aldehydes. The 18 kDa translocator protein (TSPO) is an intracellular receptor involved in proliferation and apoptosis, and has been linked to various types of cancer. The presence of TSPO in human saliva has been linked to oral cancer, and its binding affinity to its ligand is reduced following exposure to CS. In the present study we wished to further investigate the mechanism behind the CS-induced reduction of TSPO binding by exploring the possible mediatory role of reactive oxygen species (ROS) and volatile aldehydes in this process. We first analyzed TSPO binding in control saliva and in saliva exposed to CS in the presence and absence of various antioxidants. These experiments found that TSPO binding ability was not reversed by any of the antioxidants added, suggesting that CS exerts its effect on TSPO via mechanisms that do not involve volatile aldehydes and free radicals tested. Next, we analyzed TSPO binding in saliva following addition of exogenous ROS in the form of H2O2. These experiments found that TSPO binding was enhanced due to the treatment, once again showing that the CS-induced TSPO binding reduction is not mediated by this common form of ROS. However, the previously reported CS-induced reduction in salivary TSPO binding together with the role of TSPO in cells and its link to cancer strongly suggest that TSPO has a critical role in the pathogenesis of CS-induced oral cancer. The importance of further elucidating the mechanisms behind it should be emphasized.

  1. Protecting the BBB Endothelium against Cigarette Smoke-Induced Oxidative Stress Using Popular Antioxidants: Are they really beneficial?

    PubMed Central

    Kaisar, Mohammad Abul; Prasad, Shikha; Cucullo, Luca

    2015-01-01

    Blood Brain Barrier (BBB) exposed to realistic concentrations (comparable to a chronic heavy smoker) of Cigarette Smoke Extract (CSE) triggers a strong endothelial inflammatory which can lead to the onset of neurological disorders. The involvement of Reactive Oxygen Species (ROS) in this inflammatory cascade is evident from the up-regulation of nuclear factor erythroid 2 related factor 2 (Nrf-2), a transcription factor involved in anti-oxidant response signaling in CSE exposed endothelial cells. We have shown that pre-treatment with α-tocopherol and/or ascorbic acid is highly protective for the BBB, thus suggesting that, prophylactic administration of antioxidants can reduce CSE and/or inflammatory-dependent BBB damage. We have assessed and ranked the protective effects of 5 popular OTC antioxidants (Coenzyme Q10, Melatonin, Glutathione, Lipoic acid and Resveratrol) against CSE-induced BBB endothelial damage using hCMEC/D3 cells. The analysis of pro-inflammatory cytokines release by ELISA revealed that, resveratrol, lipoic acid melatonin and Co-Q10 inhibited the BBB endothelial release of pro-inflammatory cytokines IL-6 & IL-8, reduced (not Co-Q10) CSE-induced up-regulation of Platelet Endothelial Cell Adhesion Molecule -1 (PECAM-1), Vascular Endothelial Cell Adhesion Molecule-1 (VCAM-1) & E-selectin and inhibited monocytes-endothelial cell adhesion. The anti-inflammatory effects correlated with the anti-oxidative protection endowed by these compounds as evidenced by upregulation of NADPH: Quinone Oxidoreductase 1 (NQO1) and reduced cellular oxidative stress. CSE-induced release of Vascular Endothelial Growth Factor (VEGF) was inhibited by all tested compounds although the effect was not strictly dose-dependent. Further in vivo studies are required to validate our results and expand our current study to include combinatorial treatments. PMID:26410779

  2. NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes

    PubMed Central

    Das, Archita; Dey, Neekkan; Ghosh, Arunava; Das, Tanusree; Chatterjee, Indu B.

    2011-01-01

    Background The etiology of myelodysplastic syndromes (MDS) is largely unknown. Exposure to cigarette smoke (CS) is reported to be associated with MDS risk. There is inconsistent evidence that deficiency of NAD(P)H-quinone: oxidoreductase 1 (NQO1) increases the risk of MDS. Earlier we had shown that CS induces toxicity only in marginal vitamin C-deficient guinea pigs but not in vitamin C-sufficient ones. We therefore considered that NQO1 deficiency along with marginal vitamin C deficiency might produce MDS in CS-exposed guinea pigs. Methodology and Principal Findings Here we show that CS exposure for 21 days produces MDS in guinea pigs having deficiency of NQO1 (fed 3 mg dicoumarol/day) conjoint with marginal vitamin C deficiency (fed 0.5 mg vitamin C/day). As evidenced by morphology, histology and cytogenetics, MDS produced in the guinea pigs falls in the category of refractory cytopenia with unilineage dysplasia (RCUD): refractory anemia; refractory thrombocytopenia that is associated with ring sideroblasts, micromegakaryocytes, myeloid hyperplasia and aneuploidy. MDS is accompanied by increased CD34(+) cells and oxidative stress as shown by the formation of protein carbonyls and 8-oxodeoxyguanosine. Apoptosis precedes MDS but disappears later with marked decrease in the p53 protein. MDS produced in the guinea pigs are irreversible. MDS and all the aforesaid pathophysiological events do not occur in vitamin C-sufficient guinea pigs. However, after the onset of MDS vitamin C becomes ineffective. Conclusions and Significance CS exposure causes MDS in guinea pigs having deficiency of NQO1 conjoint with marginal vitamin C deficiency. The syndromes are not produced in singular deficiency of NQO1 or marginal vitamin C deficiency. Our results suggest that human smokers having NQO1 deficiency combined with marginal vitamin C deficiency are likely to be at high risk for developing MDS and that intake of a moderately large dose of vitamin C would prevent MDS. PMID:21655231

  3. Estrogen deficiency promotes cigarette smoke-induced changes in the extracellular matrix in the lungs of aging female mice.

    PubMed

    Glassberg, Marilyn K; Catanuto, Paola; Shahzeidi, Shahriar; Aliniazee, Muddassir; Lilo, Sarit; Rubio, Gustavo A; Elliot, Sharon J

    2016-12-01

    Female smokers have a faster decline in lung function with increasing age and overall develop a greater loss of lung function than male smokers. This raises the question of whether estrogen status in women affects susceptibility to cigarette smoke (CS)-induced lung disease. Mouse models suggest that female mice are more susceptible than males to CS-induced lung disease. Moreover, young CS-exposed female mice develop emphysema earlier than male mice. The purpose of this study was to characterize the relationship of estrogen status on the pattern and severity of CS-induced lung disease. In this study, 15-month-old female C57BL/6J mice were ovariectomized and administered either placebo (pla) or 17β-estradiol (E2, 0.025 mg) 2 weeks after ovariectomy. They were further divided into those that were exposed to CS and no-smoke controls (NSC). Mice were exposed to CS in stainless steel inhalation chambers 3 hours a day, 5 days a week for 6 months, and sacrificed after 24 weeks of CS exposure. Blood and urine were collected at sacrifice to measure estrogen and cotinine levels, a metabolite of nicotine. Uterine weight was recorded as an indicator of estrogen status. Results showed that CS in the absence of E2 induced a decrease in hydroxyproline content, macrophage number, and respiratory chain complex-1 protein. CS without E2 also resulted in an increase in matrix metalloproteinase-2 activity and apoptosis and a change in the ratio of estrogen receptor subtype. These findings were abrogated with administration of E2, suggesting that estrogen deficiency increases susceptibility to CS-induced lung disease.

  4. Selective inhibition by aspirin and naproxen of mainstream cigarette smoke-induced genotoxicity and lung tumors in female mice.

    PubMed

    Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Micale, Rosanna T; La Maestra, Sebastiano; D'Oria, Chiara; Steele, Vernon E; De Flora, Silvio

    2016-05-01

    The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in smoke-related lung carcinogenesis is still controversial. We have developed and validated a murine model for evaluating the tumorigenicity of mainstream cigarette smoke (MCS) and its modulation by chemopreventive agents. In the present study, the protective effects of the nonselective cyclooxygenase inhibitors aspirin and naproxen were investigated by using a total of 277 Swiss H neonatal mice of both genders. Groups of mice were exposed whole-body to MCS during the first 4 months of life, followed by an additional 3.5 months in filtered air in order to allow a better growth of tumors. Aspirin (1600 mg/kg diet) and naproxen (320 mg/kg diet) were given after weanling until the end of the experiment. After 4 months of exposure, MCS significantly enhanced the frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice, and naproxen prevented such systemic genotoxic damage in female mice. After 7.5 months, exposure of mice to MCS resulted in the formation of lung tumors, both benign and malignant, and in several other histopathological lesions detectable both in the respiratory tract and in the urinary tract. Aspirin and, even more sharply, naproxen significantly inhibited the formation of lung tumors in MCS-exposed mice, but this protective effect selectively occurred in female mice only. These results lend support to the views that estrogens are involved in smoke-related pulmonary carcinogenesis and that NSAIDs have antiestrogenic properties. The two NSAIDs proved to be safe and efficacious in the experimental model used.

  5. Protecting the BBB endothelium against cigarette smoke-induced oxidative stress using popular antioxidants: Are they really beneficial?

    PubMed

    Kaisar, Mohammad Abul; Prasad, Shikha; Cucullo, Luca

    2015-11-19

    Blood Brain Barrier (BBB) exposed to realistic concentrations (comparable to a chronic heavy smoker) of Cigarette Smoke Extract (CSE) triggers a strong endothelial inflammatory response which can lead to the onset of neurological disorders. The involvement of Reactive Oxygen Species (ROS) in this inflammatory cascade is evident from the up-regulation of nuclear factor erythroid 2 related factor 2 (Nrf-2), a transcription factor involved in anti-oxidant response signaling in CSE exposed endothelial cells. We have shown that pre-treatment with α-tocopherol and/or ascorbic acid is highly protective for the BBB, thus suggesting that, prophylactic administration of antioxidants can reduce CSE and/or inflammatory-dependent BBB damage. We have assessed and ranked the protective effects of 5 popular OTC antioxidants (Coenzyme Q10, melatonin, glutathione, lipoic acid and resveratrol) against CSE-induced BBB endothelial damage using hCMEC/D3 cells. The analysis of pro-inflammatory cytokines release by ELISA revealed that resveratrol, lipoic acid melatonin and Co-Q10 inhibited the BBB endothelial release of pro-inflammatory cytokines IL-6 and IL-8, reduced (not Co-Q10) CSE-induced up-regulation of Platelet Cell Adhesion Molecule-1 (PECAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1) & E-selectin and inhibited monocytes-endothelial cell adhesion. The anti-inflammatory effects correlated with the anti-oxidative protection endowed by these compounds as evidenced by upregulation of NADPH: Quinone Oxidoreductase 1 (NQO1) and reduced cellular oxidative stress. CSE-induced release of Vascular Endothelial Growth Factor (VEGF) was inhibited by all tested compounds although the effect was not strictly dose-dependent. Further in vivo studies are required to validate our results and expand our current study to include combinatorial treatments.

  6. RNAi Screen for NRF2 Inducers Identifies Targets That Rescue Primary Lung Epithelial Cells from Cigarette Smoke Induced Radical Stress

    PubMed Central

    Schumacher, Frances-Rose; Schubert, Steffen; Hannus, Michael; Sönnichsen, Birte; Ittrich, Carina; Kreideweiss, Stefan; Rippmann, Jörg F.

    2016-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent condition characterized by inflammation and progressive obstruction of the airways. At present, there is no treatment that suppresses the chronic inflammation of the disease, and COPD patients often succumb to the condition. Excessive oxidative stress caused by smoke inhalation is a major driving force of the disease. The transcription factor NRF2 is a critical player in the battle against oxidative stress and its function is impaired in COPD. Increasing NRF2 activity may therefore be a viable therapeutic option for COPD treatment. We show that down regulation of KEAP1, a NRF2 inhibitor, protects primary human lung epithelial cells from cigarette-smoke-extract (CSE) induced cell death in an established in vitro model of radical stress. To identify new potential drug targets with a similar effect, we performed a siRNA screen of the ‘druggable’ genome using a NRF2 transcriptional reporter cell line. This screen identified multiple genes that when down regulated increased NRF2 transcriptional activity and provided a survival benefit in the in vitro model. Our results suggest that inhibiting components of the ubiquitin-proteasome system will have the strongest effects on NRF2 transcriptional activity by increasing NRF2 levels. We also find that down regulation of the small GTPase Rab28 or the Estrogen Receptor ESRRA provide a survival benefit. Rab28 knockdown increased NRF2 protein levels, indicating that Rab28 may regulate NRF2 proteolysis. Conversely ESRRA down regulation increased NRF2 transcriptional activity without affecting NRF2 levels, suggesting a proteasome-independent mechanism. PMID:27832175

  7. Rac1 and Cdc42 differentially modulate cigarette smoke-induced airway cell migration through p120-catenin-dependent and -independent pathways.

    PubMed

    Zhang, Lili; Gallup, Marianne; Zlock, Lorna; Finkbeiner, Walter E; McNamara, Nancy A

    2013-06-01

    The adherens junction protein p120-catenin (p120ctn) shuttles between E-cadherin-bound and cytoplasmic pools to regulate E-cadherin/catenin complex stability and cell migration, respectively. When released from the adherens junction, p120ctn promotes cell migration through modulation of the Rho GTPases Rac1, Cdc42, and RhoA. Accordingly, the down-regulation and cytoplasmic mislocalization of p120ctn has been reported in all subtypes of lung cancers and is associated with grave prognosis. Previously, we reported that cigarette smoke induced cytoplasmic translocation of p120ctn and cell migration, but the underlying mechanism was unclear. Using primary human bronchial epithelial cells exposed to smoke-concentrated medium (Smk), we observed the translocation of Rac1 and Cdc42, but not RhoA, to the leading edge of polarized and migrating human bronchial epithelial cells. Rac1 and Cdc42 were robustly activated by smoke, whereas RhoA was inhibited. Accordingly, siRNA knockdown of Rac1 or Cdc42 completely abolished Smk-induced cell migration, whereas knockdown of RhoA had no effect. p120ctn/Rac1 double knockdown completely abolished Smk-induced cell migration, whereas p120ctn/Cdc42 double knockdown did not. These data suggested that Rac1 and Cdc42 coactivation was essential to smoke-promoted cell migration in the presence of p120ctn, whereas migration proceeded via Rac1 alone in the absence of p120ctn. Thus, Rac1 may provide an omnipotent therapeutic target in reversing cell migration during the early (intact p120ctn) and late (loss of p120ctn) stages of lung carcinogenesis.

  8. The Acute Impact of Smoking One Cigarette on Cardiac Hemodynamic Parameters

    PubMed Central

    Farha, Khalid Abou; AbouFarha, Ramy; Bolt, Marc

    2011-01-01

    Background The acute impact of tobacco smoking on the cardiac hemodynamic parameters and its pathological implication in the process of arterial atherosclerosis need further exploration. This investigation was purposed to assess the acute impact of tobacco smoke on blood pressure and cardiac hemodynamic parameters. Methods Using an Ultrasonic Cardiac Output Monitor, and DINAMAP Pro 400 Series V2 blood pressure monitor, several cardiac hemodynamic parameters and the blood pressure were assessed in 14 smokers, 11 females and 3 males, at 2 time points, before and after smoking of one cigarette. Data, in terms of ratio of the means and 95% confidence interval were analyzed using ANOVA. Results Single-subject design in which the subject has served as his/her own control has been used. Tobacco smoking led to statistically significant acute increase in the means of all hemodynamic parameters, except for heart rate in female subjects, as compared to the means obtained before smoking. Conclusions Cigarette smoking induces acute non-physiologic alteration in cardiac outflow forces, exposing the aortic valve and arch to mechanical injury that might be implicated in initiating and promoting the process of aortic arch atherosclerosis and associated pathological lesions.

  9. 32P-postlabeling DNA adduct assay: cigarette smoke-induced dna adducts in the respiratory and nonrespiratory rat tissues. Book chapter

    SciTech Connect

    Gupta, R.C.; Gairola, C.G.

    1990-01-01

    An analysis of the tissue DNA adducts in rats by the sensitive (32)p-postlabeling assay showed one to eight detectable DNA adducts in lung, trachea, larynx, heart and bladder of the sham controls. Chronic exposure of animals to mainstream cigarette smoke showed a remarkable enhancement of most adducts in the lung and heart DNA. Since cigarette smoke contains several thousand chemicals and a few dozen of them are known or potential carcinogens, the difference between the DNA adducts of nasal and the other tissues may reflect the diversity of reactive constituents and their differential absorption in different tissues. In comparison to the lung DNA adducts, the adducts in nasal DNA were less hydrophobic. Identity of the predominant adducts was further investigated by comparison with several reference DNA adducts from 10 PAH and aromatic amines. Since some of these chemicals are present in cigarette smoke, the results suggest that these constituents of cigarette smoke may not be directly responsible for formation of DNA adducts in the lung and heart of the smoke-exposed animals.

  10. Cigarette smoke induces proteasomal-mediated degradation of DNA methyltransferases and methyl CpG-/CpG domain-binding proteins in embryonic orofacial cells.

    PubMed

    Mukhopadhyay, Partha; Greene, Robert M; Pisano, M Michele

    2015-12-01

    Orofacial clefts, the most prevalent of developmental anomalies, occur with a frequency of 1 in 700 live births. Maternal cigarette smoking during pregnancy represents a risk factor for having a child with a cleft lip and/or cleft palate. Using primary cultures of first branchial arch-derived cells (1-BA cells), which contribute to the formation of the lip and palate, the present study addressed the hypothesis that components of cigarette smoke alter global DNA methylation, and/or expression of DNA methyltransferases (Dnmts) and various methyl CpG-binding proteins. Primary cultures of 1-BA cells, exposed to 80μg/mL cigarette smoke extract (CSE) for 24h, exhibited a >13% decline in global DNA methylation and triggered proteasomal-mediated degradation of Dnmts (DNMT-1 and -3a), methyl CpG binding protein 2 (MeCP2) and methyl-CpG binding domain protein 3 (MBD-3). Pretreatment of 1-BA cells with the proteasomal inhibitor MG-132 completely reversed such degradation. Collectively, these data allow the suggestion of a potential epigenetic mechanism underlying maternal cigarette smoke exposure-induced orofacial clefting.

  11. CIGARETTE SMOKE INDUCES PROTEASOMAL-MEDIATED DEGRADATION OF DNA METHYLTRANSFERASES AND METHYL CpG-/CpG DOMAIN-BINDING PROTEINS IN EMBRYONIC OROFACIAL CELLS

    PubMed Central

    Mukhopadhyay, Partha; Greene, Robert M.; Pisano, M. Michele

    2015-01-01

    Orofacial clefts, the most prevalent of developmental anomalies, occur with a frequency of 1 in 700 live births. Maternal cigarette smoking during pregnancy represents a risk factor for having a child with a cleft lip and/or cleft palate. Using primary cultures of first branchial arch-derived cells (1-BA cells), which contribute to the formation of the lip and palate, the present study addressed the hypothesis that components of cigarette smoke alter global DNA methylation, and/or expression of DNA methyltransferases (Dnmts) and various methyl CpG-binding proteins. Primary cultures of 1-BA cells, exposed to 80 μg/ml cigarette smoke extract (CSE) for 24 hrs, exhibited a >13% decline in global DNA methylation and triggered proteasomal-mediated degradation of Dnmts (DNMT-1, and - 3a), methyl CpG binding protein 2 (MeCP2) and methyl-CpG binding domain protein 3 (MBD-3). Pretreatment of 1-BA cells with the proteasomal inhibitor MG-132 completely reversed such degradation. Collectively, these data allow the suggestion of a potential epigenetic mechanism underlying maternal cigarette smoke exposure-induced orofacial clefting. PMID:26482727

  12. Lung injury and lung cancer caused by cigarette smoke-induced oxidative stress: Molecular mechanisms and therapeutic opportunities involving the ceramide-generating machinery and epidermal growth factor receptor.

    PubMed

    Goldkorn, Tzipora; Filosto, Simone; Chung, Samuel

    2014-11-20

    Chronic obstructive pulmonary disease (COPD) and lung cancer are frequently caused by tobacco smoking. However, these diseases present opposite phenotypes involving redox signaling at the cellular level. While COPD is characterized by excessive airway epithelial cell death and lung injury, lung cancer is caused by uncontrolled epithelial cell proliferation. Notably, epidemiological studies have demonstrated that lung cancer incidence is significantly higher in patients who have preexisting emphysema/lung injury. However, the molecular link and common cell signaling events underlying lung injury diseases and lung cancer are poorly understood. This review focuses on studies of molecular mechanism(s) underlying smoking-related lung injury (COPD) and lung cancer. Specifically, the role of the ceramide-generating machinery during cigarette smoke-induced oxidative stress leading to both apoptosis and proliferation of lung epithelial cells is emphasized. Over recent years, it has been established that ceramide is a sphingolipid playing a major role in lung epithelia structure/function leading to lung injury in chronic pulmonary diseases. However, new and unexpected findings draw attention to its potential role in lung development, cell proliferation, and tumorigenesis. To address this dichotomy in detail, evidence is presented regarding several protein targets, including Src, p38 mitogen-activated protein kinase, and neutral sphingomyelinase 2, the major sphingomyelinase that controls ceramide generation during oxidative stress. Furthermore, their roles are presented not only in apoptosis and lung injury but also in enhancing cell proliferation, lung cancer development, and resistance to epidermal growth factor receptor-targeted therapy for treating lung cancer.

  13. Mithramycin represses basal and cigarette smoke-induced expression of ABCG2 and inhibits stem cell signaling in lung and esophageal cancer cells.

    PubMed

    Zhang, Mary; Mathur, Aarti; Zhang, Yuwei; Xi, Sichuan; Atay, Scott; Hong, Julie A; Datrice, Nicole; Upham, Trevor; Kemp, Clinton D; Ripley, R Taylor; Wiegand, Gordon; Avital, Itzak; Fetsch, Patricia; Mani, Haresh; Zlott, Daniel; Robey, Robert; Bates, Susan E; Li, Xinmin; Rao, Mahadev; Schrump, David S

    2012-08-15

    Cigarette smoking at diagnosis or during therapy correlates with poor outcome in patients with lung and esophageal cancers, yet the underlying mechanisms remain unknown. In this study, we observed that exposure of esophageal cancer cells to cigarette smoke condensate (CSC) led to upregulation of the xenobiotic pump ABCG2, which is expressed in cancer stem cells and confers treatment resistance in lung and esophageal carcinomas. Furthermore, CSC increased the side population of lung cancer cells containing cancer stem cells. Upregulation of ABCG2 coincided with increased occupancy of aryl hydrocarbon receptor, Sp1, and Nrf2 within the ABCG2 promoter, and deletion of xenobiotic response elements and/or Sp1 sites markedly attenuated ABCG2 induction. Under conditions potentially achievable in clinical settings, mithramycin diminished basal as well as CSC-mediated increases in AhR, Sp1, and Nrf2 levels within the ABCG2 promoter, markedly downregulated ABCG2, and inhibited proliferation and tumorigenicity of lung and esophageal cancer cells. Microarray analyses revealed that mithramycin targeted multiple stem cell-related pathways in vitro and in vivo. Collectively, our findings provide a potential mechanistic link between smoking status and outcome of patients with lung and esophageal cancers, and support clinical use of mithramycin for repressing ABCG2 and inhibiting stem cell signaling in thoracic malignancies.

  14. Inhibition of monoamine oxidase-B by selegiline reduces cigarette smoke-induced oxidative stress and inflammation in airway epithelial cells.

    PubMed

    Cui, Yuting; Liu, Kenneth W K; Liang, Yingmin; Ip, Mary S M; Mak, Judith C W

    2017-02-15

    Chronic obstructive pulmonary disease (COPD) is caused by the build-up of oxidative stress-induced damages due to cigarette smoking, but how monoamine oxidase (MAO)-B signaling is involved remains unclear. This study aims to establish the involvement of MAO-B signaling pathways in cigarette smoke medium (CSM)-induced oxidative stress and inflammation in human airway epithelial cells (AECs). CSM treatment increased MAO-B activity, ROS levels and IL-8 release in AECs. Pretreatment with MAO-B selective inhibitor selegiline reversed the CSM-induced changes in MAO-B activity, ROS levels and IL-8 release in a dose-dependent manner. Selegiline also reversed CSM-induced changes of anti-oxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activities, GSH/GSSG ratio, as well expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). The effects of selegiline are partially driven through the nuclear factor erythroid 2 related factor 2 (Nrf2) and cytosol translocation of its negative regulator, BTB and CNC homolog 1 (Bach1). Nevertheless, selegiline fully reversed the CSM-induced effects on IKK, cytoplasmic IκB expression, and nuclear translocation of nuclear factor-κB (NF-κB) p65 subunit. Our study demonstrated that in AECs, inhibition of MAO-B using selegiline reversed the CSM-induced oxidative stress and inflammation. These data may provide a novel strategy for therapy in COPD.

  15. Cigarette smoke induced genotoxicity and respiratory tract pathology: evidence to support reduced exposure time and animal numbers in tobacco product testing.

    PubMed

    Dalrymple, Annette; Ordoñez, Patricia; Thorne, David; Walker, David; Camacho, Oscar M; Büttner, Ansgar; Dillon, Debbie; Meredith, Clive

    2016-06-01

    Many laboratories are working to develop in vitro models that will replace in vivo tests, but occasionally there remains a regulatory expectation of some in vivo testing. Historically, cigarettes have been tested in vivo for 90 days. Recently, methods to reduce and refine animal use have been explored. This study investigated the potential of reducing animal cigarette smoke (CS) exposure to 3 or 6 weeks, and the feasibility of separate lung lobes for histopathology or the Comet assay. Rats were exposed to sham air or CS (1 or 2 h) for 3 or 6 weeks. Respiratory tissues were processed for histopathological evaluation, and Alveolar type II cells (AEC II) isolated for the Comet assay. Blood was collected for Pig-a and micronucleus quantification. Histopathological analyses demonstrated exposure effects, which were generally dependent on CS dose (1 or 2 h, 5 days/week). Comet analysis identified that DNA damage increased in AEC II following 3 or 6 weeks CS exposure, and the level at 6 weeks was higher than 3 weeks. Pig-a mutation or micronucleus levels were not increased. In conclusion, this study showed that 3 weeks of CS exposure was sufficient to observe respiratory tract pathology and DNA damage in isolated AEC II. Differences between the 3 and 6 week data imply that DNA damage in the lung is cumulative. Reducing exposure time, plus analyzing separate lung lobes for DNA damage or histopathology, supports a strategy to reduce and refine animal use in tobacco product testing and is aligned to the 3Rs (replacement, reduction and refinement).

  16. Antrodia camphorata attenuates cigarette smoke-induced ROS production, DNA damage, apoptosis, and inflammation in vascular smooth muscle cells, and atherosclerosis in ApoE-deficient mice.

    PubMed

    Yang, Hsin-Ling; Korivi, Mallikarjuna; Chen, Cheng-Hsien; Peng, Wei-Jung; Chen, Chee-Shan; Li, Mei-Ling; Hsu, Li-Sung; Liao, Jiunn-Wang; Hseu, You-Cheng

    2017-04-03

    Cigarette smoke exposure activates several cellular mechanisms predisposing to atherosclerosis, including oxidative stress, dyslipidemia, and vascular inflammation. Antrodia camphorata, a renowned medicinal mushroom in Taiwan, has been investigated for its antioxidant, anti-inflammatory, and antiatherosclerotic properties in cigarette smoke extracts (CSE)-treated vascular smooth muscle cells (SMCs), and ApoE-deficient mice. Fermented culture broth of Antrodia camphorata (AC, 200-800 µg/mL) possesses effective antioxidant activity against CSE-induced ROS production. Treatment of SMCs (A7r5) with AC (30-120 µg/mL) remarkably ameliorated CSE-induced morphological aberrations and cell death. Suppressed ROS levels by AC corroborate with substantial inhibition of CSE-induced DNA damage in AC-treated A7r5 cells. We found CSE-induced apoptosis through increased Bax/Bcl-2 ratio, was substantially inhibited by AC in A7r5 cells. Notably, upregulated SOD and catalase expressions in AC-treated A7r5 cells perhaps contributed to eradicate the CSE-induced ROS generation, and prevents DNA damage and apoptosis. Besides, AC suppressed AP-1 activity by inhibiting the c-Fos/c-Jun expressions, and NF-κB activation through inhibition of I-κBα degradation against CSE-stimulation. This anti-inflammatory property of AC was accompanied by suppressed CSE-induced VEGF, PDGF, and EGR-1 overexpressions in A7r5 cells. Furthermore, AC protects lung fibroblast (MRC-5) cells from CSE-induced cell death. In vivo data showed that AC oral administration (0.6 mg/d/8-wk) prevents CSE-accelerated atherosclerosis in ApoE-deficient mice. This antiatherosclerotic property was associated with increased serum total antioxidant status, and decreased total cholesterol and triacylglycerol levels. Thus, Antrodia camphorata may be useful for prevention of CSE-induced oxidative stress and diseases.

  17. Cigarette smoke induced genotoxicity and respiratory tract pathology: evidence to support reduced exposure time and animal numbers in tobacco product testing

    PubMed Central

    Dalrymple, Annette; Ordoñez, Patricia; Thorne, David; Walker, David; Camacho, Oscar M.; Büttner, Ansgar; Dillon, Debbie; Meredith, Clive

    2016-01-01

    Abstract Many laboratories are working to develop in vitro models that will replace in vivo tests, but occasionally there remains a regulatory expectation of some in vivo testing. Historically, cigarettes have been tested in vivo for 90 days. Recently, methods to reduce and refine animal use have been explored. This study investigated the potential of reducing animal cigarette smoke (CS) exposure to 3 or 6 weeks, and the feasibility of separate lung lobes for histopathology or the Comet assay. Rats were exposed to sham air or CS (1 or 2 h) for 3 or 6 weeks. Respiratory tissues were processed for histopathological evaluation, and Alveolar type II cells (AEC II) isolated for the Comet assay. Blood was collected for Pig-a and micronucleus quantification. Histopathological analyses demonstrated exposure effects, which were generally dependent on CS dose (1 or 2 h, 5 days/week). Comet analysis identified that DNA damage increased in AEC II following 3 or 6 weeks CS exposure, and the level at 6 weeks was higher than 3 weeks. Pig-a mutation or micronucleus levels were not increased. In conclusion, this study showed that 3 weeks of CS exposure was sufficient to observe respiratory tract pathology and DNA damage in isolated AEC II. Differences between the 3 and 6 week data imply that DNA damage in the lung is cumulative. Reducing exposure time, plus analyzing separate lung lobes for DNA damage or histopathology, supports a strategy to reduce and refine animal use in tobacco product testing and is aligned to the 3Rs (replacement, reduction and refinement). PMID:27160659

  18. Systems Biology Reveals Cigarette Smoke-Induced Concentration-Dependent Direct and Indirect Mechanisms That Promote Monocyte-Endothelial Cell Adhesion.

    PubMed

    Poussin, Carine; Laurent, Alexandra; Peitsch, Manuel C; Hoeng, Julia; De Leon, Hector

    2015-10-01

    Cigarette smoke (CS) affects the adhesion of monocytes to endothelial cells, a critical step in atherogenesis. Using an in vitro adhesion assay together with innovative computational systems biology approaches to analyze omics data, our study aimed at investigating CS-induced mechanisms by which monocyte-endothelial cell adhesion is promoted. Primary human coronary artery endothelial cells (HCAECs) were treated for 4 h with (1) conditioned media of human monocytic Mono Mac-6 (MM6) cells preincubated with low or high concentrations of aqueous CS extract (sbPBS) from reference cigarette 3R4F for 2 h (indirect treatment, I), (2) unconditioned media similarly prepared without MM6 cells (direct treatment, D), or (3) freshly generated sbPBS (fresh direct treatment, FD). sbPBS promoted MM6 cells-HCAECs adhesion following I and FD, but not D. In I, the effect was mediated at a low concentration through activation of vascular inflammation processes promoted in HCAECs by a paracrine effect of the soluble mediators secreted by sbPBS-treated MM6 cells. Tumor necrosis factor α (TNFα), a major inducer, was actually shed by unstable CS compound-activated TNFα-converting enzyme. In FD, the effect was triggered at a high concentration that also induced some toxicity. This effect was mediated through an yet unknown mechanism associated with a stress damage response promoted in HCAECs by unstable CS compounds present in freshly generated sbPBS, which had decayed in D unconditioned media. Aqueous CS extract directly and indirectly promotes monocytic cell-endothelial cell adhesion in vitro via distinct concentration-dependent mechanisms.

  19. Dietary Monascus adlay supplements facilitate suppression of cigarette smoke-induced pulmonary endoplasmic reticulum stress, autophagy, apoptosis and emphysema-related PLGF in the rat.

    PubMed

    Li, Ping-Chia; Tsai, Wen-Hsin; Chien, Chiang-Ting

    2013-01-15

    Cigarette smoke (CS) exposure may cause oxidative stress in the lung, leading to cell death and long-term injury. Monascus adlay (MA) with antioxidant components produced by inoculating adlay (Cois lachrymal-jobi L. var. ma-yuen Stapf) with Monascus purpureus may protect lung against CS-induced lung injuries in rats. MA and lovastatin had higher antioxidant activities than either M. purpureus or adlay. CS exposure caused significant lung damage, as evidenced by higher levels of reactive oxygen species (ROS), neutrophil infiltration, dityrosine and 4-HNE, as well as lower levels of Mn-superoxide dismutase and catalase expression. Lung tissues with CS exposure had higher levels of ER stress, apoptosis, autophagy and emphysema-related placenta growth factor (PlGF) expressions. All CS-induced injuries were significantly suppressed by MA supplements. MA would be a beneficial nutritional therapy to ameliorate CS-induced lung injury via preserving antioxidant defense mechanisms, decreasing oxidative stress and inhibiting ER stress, autophagy, apoptosis and emphysema-related risk factor.

  20. HDAC1-3 inhibitor MS-275 enhances IL10 expression in RAW264.7 macrophages and reduces cigarette smoke-induced airway inflammation in mice

    PubMed Central

    Leus, Niek G. J.; van den Bosch, Thea; van der Wouden, Petra E.; Krist, Kim; Ourailidou, Maria E.; Eleftheriadis, Nikolaos; Kistemaker, Loes E. M.; Bos, Sophie; Gjaltema, Rutger A. F.; Mekonnen, Solomon A.; Bischoff, Rainer; Gosens, Reinoud; Haisma, Hidde J.; Dekker, Frank J.

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) constitutes a major health burden. Studying underlying molecular mechanisms could lead to new therapeutic targets. Macrophages are orchestrators of COPD, by releasing pro-inflammatory cytokines. This process relies on transcription factors such as NF-κB, among others. NF-κB is regulated by lysine acetylation; a post-translational modification installed by histone acetyltransferases and removed by histone deacetylases (HDACs). We hypothesized that small molecule HDAC inhibitors (HDACi) targeting class I HDACs members that can regulate NF-κB could attenuate inflammatory responses in COPD via modulation of the NF-κB signaling output. MS-275 is an isoform-selective inhibitor of HDAC1-3. In precision-cut lung slices and RAW264.7 macrophages, MS-275 upregulated the expression of both pro- and anti-inflammatory genes, implying mixed effects. Interestingly, anti-inflammatory IL10 expression was upregulated in these model systems. In the macrophages, this was associated with increased NF-κB activity, acetylation, nuclear translocation, and binding to the IL10 promoter. Importantly, in an in vivo model of cigarette smoke-exposed C57Bl/6 mice, MS-275 robustly attenuated inflammatory expression of KC and neutrophil influx in the lungs. This study highlights for the first time the potential of isoform-selective HDACi for the treatment of inflammatory lung diseases like COPD. PMID:28344354

  1. Oral N-acetylcysteine or S-carboxymethylcysteine inhibit cigarette smoke-induced hypersecretion of mucus in rat larynx and trachea in situ.

    PubMed

    Rogers, D F; Turner, N C; Marriott, C; Jeffery, P K

    1989-11-01

    Two weeks exposure of rats to cigarette smoke (CS) significantly (p less than 0.05) increased the secretion of fucose-containing glycoconjugates above normal in an in situ preparation of larynx and trachea. After equilibration mean basal secretion in CS-exposed rats was 24 micrograms (per 30 min collection) which was 8 times higher than that of unexposed animals (p less than 0.01). N-acetylcysteine (NAC) or S-carboxymethylcysteine (SCMC) given as 1% of the drinking water, before and after daily exposure to CS, significantly inhibited the development of the CS-induced increase in fucose secretion reducing the mean for basal secretion in each group to 7 and 5 micrograms, respectively (p less than 0.05). Neither NAC nor SCMC had significant effects on baseline glycoconjugate secretion in control animals. Albumin was inconsistently present in the secretions of both control and CS-exposed animals, whereas in those exposed to CS and also given one of the two cysteine derivatives there was a consistent increase in albumin transudation.

  2. Cigarette-smoke-induced atherogenic lipid profiles in plasma and vascular tissue of apolipoprotein E-deficient mice are attenuated by smoking cessation.

    PubMed

    Lietz, Michael; Berges, An; Lebrun, Stefan; Meurrens, Kris; Steffen, Yvonne; Stolle, Katrin; Schueller, Jutta; Boue, Stephanie; Vuillaume, Grégory; Vanscheeuwijck, Patrick; Moehring, Michaela; Schlage, Walter; De Leon, Hector; Hoeng, Julia; Peitsch, Manuel

    2013-07-01

    Tobacco smoke exerts perturbations on lipid metabolism and arterial cell function that accelerate atherosclerosis. Lipidomics has emerged as a key technology in helping to elucidate the lipid-related mechanisms of atherosclerosis. In this study, we investigated the effects of smoking cessation on plaque development and aortic arch content of various lipid molecular classes and species. Apolipoprotein E-deficient mice were exposed to fresh air (sham) or to mainstream cigarette smoke (CS) for 6 months, or to CS for 3 months followed by sham for 3 months (cessation group). Lipids from plasma and aortic arches, plasma lipoprotein profiles and plaque morphometry measurements were analyzed. We already showed that CS exposure accelerated plaque size and total cholesterol content of the aortic arch at 3 and 6 months. Marked increases were seen in the relative enrichment of cholesteryl esters, phospholipids, sphingomyelins, and glycosphingolipids. Smoking cessation slowed plaque progression and resulted in lower levels of many lipid species in plasma and aortic arch. While CS exposure promoted rapid lipid accumulation in mouse aorta, smoking cessation translated into a slow removal of lipids from the vessel wall. Despite the smoking cessation-dependent metabolic changes leading to increased animal body weight, accumulation of proatherogenic lipids in the vessel was halted after exposure cessation, indicating that the clinical benefits of smoking cessation translate directly to the vessel wall and its lipid makeup.

  3. Reduced nuclear translocation of serum response factor is associated with skeletal muscle atrophy in a cigarette smoke-induced mouse model of COPD

    PubMed Central

    Ma, Ran; Gong, Xuefang; Jiang, Hua; Lin, Chunyi; Chen, Yuqin; Xu, Xiaoming; Zhang, Chenting; Wang, Jian; Lu, Wenju; Zhong, Nanshan

    2017-01-01

    Skeletal muscle atrophy and dysfunction are common complications in the chronic obstructive pulmonary disease (COPD). However, the underlying molecular mechanism remains elusive. Serum response factor (SRF) is a transcription factor which is critical in myocyte differentiation and growth. In this study, we established a mouse COPD model induced by cigarette smoking (CS) exposure for 24 weeks, with apparent pathophysiological changes, including increased airway resistance, enlarged alveoli, and skeletal muscle atrophy. Levels of upstream regulators of SRF, striated muscle activator of Rho signaling (STARS), and ras homolog gene family, member A (RhoA) were decreased in quadriceps muscle of COPD mice. Meanwhile, the nucleic location of SRF was diminished along with its cytoplasmic accumulation. There was a downregulation of the target muscle-specific gene, Igf1. These results suggest that the CS is one of the major causes for COPD pathogenesis, which induces the COPD-associated skeletal muscle atrophy which is closely related to decreasing SRF nucleic translocation, consequently downregulating the SRF target genes involved in muscle growth and nutrition. The STARS/RhoA signaling pathway might contribute to this course by impacting SRF subcellular distribution. PMID:28260872

  4. Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling.

    PubMed

    Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future.

  5. Taraxasterol inhibits cigarette smoke-induced lung inflammation by inhibiting reactive oxygen species-induced TLR4 trafficking to lipid rafts.

    PubMed

    Xueshibojie, Liu; Duo, Yu; Tiejun, Wang

    2016-10-15

    Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been demonstrated to have anti-inflammatory effects. However, the protective effects of taraxasterol against cigarette smoke (CS)-induced lung inflammation have not been reported. This study aimed to investigate the protective effects and mechanism of taraxasterol on CS-induced lung inflammation in mice. CS-induced mouse lung inflammation model was used to investigate the protective effects of taraxasterol in vivo. Human bronchial epithelial cells (HBECs) were used to investigate the protective mechanism of taraxasterol in vitro. The results showed that taraxasterol attenuated CS-induced lung pathological changes, inflammatory cells infiltration, inflammatory cytokines TNF-α, IL-6 and IL-1β production. Taraxasterol also up-regulated CS-induced glutathione (GSH) production. In vitro, taraxasterol was found to inhibit CS-induced reactive oxygen species production, recruitment of TLR4 into lipid rafts, NF-κB activation, and IL-8 production. Furthermore, our results showed that antioxidant N-acetyl-L-cysteine (NAC) significantly inhibited CS-induced recruitment of TLR4 into lipid rafts as well as IL-8 production. In conclusion, our results suggested that taraxasterol had protective effects of CS-induced lung inflammation.

  6. Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling

    PubMed Central

    Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future. PMID:27669518

  7. iPSC-derived mesenchymal stem cells exert SCF-dependent recovery of cigarette smoke-induced apoptosis/proliferation imbalance in airway cells.

    PubMed

    Li, Xiang; Zhang, Yuelin; Liang, Yingmin; Cui, Yuting; Yeung, Sze C; Ip, Mary S M; Tse, Hung-Fat; Lian, Qizhou; Mak, Judith C W

    2017-02-01

    Mesenchymal stem cells (MSCs) have emerged as a potential cell-based therapy for pulmonary emphysema in animal models. Our previous study demonstrated that human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) were superior over bone marrow-derived MSCs (BM-MSCs) in attenuating cigarette smoke (CS)-induced airspace enlargement possibly through mitochondrial transfer. This study further investigated the effects of iPSC-MSCs on inflammation, apoptosis, and proliferation in a CS-exposed rat model and examined the effects of the secreted paracrine factor from MSCs as another possible mechanism in an in vitro model of bronchial epithelial cells. Rats were exposed to 4% CS for 1 hr daily for 56 days. At days 29 and 43, human iPSC-MSCs or BM-MSCs were administered intravenously. We observed significant attenuation of CS-induced elevation of circulating 8-isoprostane and cytokine-induced neutrophil chemoattractant-1 after iPSC-MSC treatment. In line, a superior capacity of iPSC-MSCs was also observed in ameliorating CS-induced infiltration of macrophages and neutrophils and apoptosis/proliferation imbalance in lung sections over BM-MSCs. In support, the conditioned medium (CdM) from iPSC-MSCs ameliorated CS medium-induced apoptosis/proliferation imbalance of bronchial epithelial cells in vitro. Conditioned medium from iPSC-MSCs contained higher level of stem cell factor (SCF) than that from BM-MSCs. Deprivation of SCF from iPSC-MSC-derived CdM led to a reduction in anti-apoptotic and pro-proliferative capacity. Taken together, our data suggest that iPSC-MSCs may possess anti-apoptotic/pro-proliferative capacity in the in vivo and in vitro models of CS-induced airway cell injury partly through paracrine secretion of SCF.

  8. Crystal amphetamine smoking-induced acute eosinophilic pneumonia and diffuse alveolar damage: a case report and literature review.

    PubMed

    Lin, Shih-Sen; Chen, Yu-Ching; Chang, Yih-Leong; Yeh, Diana Yu-Wung; Lin, Chen-Chun

    2014-10-31

    Eosinophilic pneumonia (EP) is a disease characterized by prominent infiltration of lung structures by eosinophils. The lung interstitium is infiltrated by eosinophils, and essentially the alveolar spaces are filled with eosinophils and a fibrinous exudate, with conservation of the global architecture of the lung. Diagnosis of EP relies on pathological demonstration of alveolar eosinophilia along with characteristic clinical manifestations of nonproductive cough, dyspnea, chest pain and/or unique imaging features. EP may be categorized according to the origin: EP of undetermined origin may overlap with well-individualized syndromes, while EP with a definite cause are mainly due to infections or drug abuse. Here, we report a case of an amphetamine abuser who developed acute EP and acute respiratory distress syndrome after amphetamine inhalation. Related studies on the pathogenesis of stimulant-related lung injury and treatment strategies are also discussed.

  9. Acute effects of electronic and tobacco cigarette smoking on complete blood count.

    PubMed

    Flouris, Andreas D; Poulianiti, Konstantina P; Chorti, Maria S; Jamurtas, Athanasios Z; Kouretas, Dimitrios; Owolabi, Emmanuel O; Tzatzarakis, Manolis N; Tsatsakis, Aristidis M; Koutedakis, Yiannis

    2012-10-01

    The World Health Organisation called for research assessing the safety of electronic cigarette (e-cigarette). We evaluated the acute effect of active and passive e-cigarette and tobacco cigarette smoking on complete blood count (CBC) markers in 15 smokers and 15 never-smokers, respectively. Smokers underwent a control session, an active tobacco cigarette smoking session, and an active e-cigarette smoking session. Never-smokers underwent a control session, a passive tobacco cigarette smoking session, and a passive e-cigarette smoking session. The results demonstrated that CBC indices remained unchanged during the control session and the active and passive e-cigarette smoking sessions (P>0.05). Active and passive tobacco cigarette smoking increased white blood cell, lymphocyte, and granulocyte counts for at least one hour in smokers and never smokers (P<0.05). It is concluded that acute active and passive smoking using the e-cigarettes tested in the current study does not influence CBC indices in smokers and never smokers, respectively. In contrast, acute active and passive tobacco cigarette smoking increase the secondary proteins of acute inflammatory load for at least one hour. More research is needed to evaluate chemical safety issues and other areas of consumer product safety of e-cigarettes, because the nicotine content in the liquids used may vary considerably.

  10. Acute effects of cigarette smoking on pattern electroretinogram.

    PubMed

    Gundogan, Fatih C; Durukan, A Hakan; Mumcuoglu, Tarkan; Sobaci, Gungor; Bayraktar, M Zeki

    2006-09-01

    In this study, acute effects of cigarette smoking on the pattern electroretinogram (PERG) were investigated. First, variability of the PERG was studied in a group of young male smokers (26 right eyes of 26 subjects). Then PERGs were investigated in a group of habitual smokers (17 right eyes of 17 subjects) in separate real smoking and sham smoking sessions. On each session PERGs were recorded pre-smoking (PS), immediately after smoking (IAS) and 5 min after smoking (5th) conditions. Real smoking significantly increased P50 amplitudes and decreased N95 latencies. Regarding P50 amplitudes in the real smoking sessions, the differences were significant between PS and IAS (PS: 3.3 +/- 0.5 muV, IAS: 3.7 +/- 0.7microV, P = 0.015) and between PS-5th (PS: 3.3 +/- 0.5microV, 5th: 4.1 +/- 0.9microV, P = 0.039). There was significant difference (P = 0.024) between N95 latencies of PS (98.5 +/- 6.9 ms) and IAS (94.7 +/- 5.1 ms) in the real smoking sessions. No statistically significant difference was observed in sham smoking sessions. Our results indicated, for the first time, that cigarette smoking may influence PERG amplitude and latency significantly in habitual smokers.

  11. Acute effects of cigarette smoke exposure on experimental skin flaps

    SciTech Connect

    Nolan, J.; Jenkins, R.A.; Kurihara, K.; Schultz, R.C.

    1985-04-01

    Random vascular patterned caudally based McFarlane-type skin flaps were elevated in groups of Fischer 344 rats. Groups of rats were then acutely exposed on an intermittent basis to smoke generated from well-characterized research filter cigarettes. Previously developed smoke inhalation exposure protocols were employed using a Maddox-ORNL inhalation exposure system. Rats that continued smoke exposure following surgery showed a significantly greater mean percent area of flap necrosis compared with sham-exposed groups or control groups not exposed. The possible pathogenesis of this observation as well as considerations and correlations with chronic human smokers are discussed. Increased risks of flap necrosis by smoking in the perioperative period are suggested by this study.

  12. Inflammatory Transcriptome Profiling of Human Monocytes Exposed Acutely to Cigarette Smoke

    PubMed Central

    Wright, William R.; Parzych, Katarzyna; Crawford, Damian; Mein, Charles; Mitchell, Jane A.; Paul-Clark, Mark J.

    2012-01-01

    Background Cigarette smoking is responsible for 5 million deaths worldwide each year, and is a major risk factor for cardiovascular and lung diseases. Cigarette smoke contains a complex mixture of over 4000 chemicals containing 1015 free radicals. Studies show smoke is perceived by cells as an inflammatory and xenobiotic stimulus, which activates an immune response. The specific cellular mechanisms driving cigarette smoke-induced inflammation and disease are not fully understood, although the innate immune system is involved in the pathology of smoking related diseases. Methodology/Principle findings To address the impact of smoke as an inflammagen on the innate immune system, THP-1 cells and Human PBMCs were stimulated with 3 and 10% (v/v) cigarette smoke extract (CSE) for 8 and 24 hours. Total RNA was extracted and the transcriptome analysed using Illumina BeadChip arrays. In THP-1 cells, 10% CSE resulted in 80 genes being upregulated and 37 downregulated by ≥1.5 fold after 8 hours. In PBMCs stimulated with 10% CSE for 8 hours, 199 genes were upregulated and 206 genes downregulated by ≥1.5 fold. After 24 hours, the number of genes activated and repressed by ≥1.5 fold had risen to 311 and 306 respectively. The major pathways that were altered are associated with cell survival, such as inducible antioxidants, protein chaperone and folding proteins, and the ubiquitin/proteosome pathway. Conclusions Our results suggest that cigarette smoke causes inflammation and has detrimental effects on the metabolism and function of innate immune cells. In addition, THP-1 cells provide a genetically stable alternative to primary cells for the study of the effects of cigarette smoke on human monocytes. PMID:22363418

  13. Prevalence and Impact of Active and Passive Cigarette Smoking in Acute Respiratory Distress Syndrome

    PubMed Central

    Hsieh, S. Jean; Zhuo, Hanjing; Benowitz, Neal L.; Thompson, B. Taylor; Liu, Kathleen D.; Matthay, Michael A.; Calfee, Carolyn S.

    2014-01-01

    Objective Cigarette smoke exposure has recently been found to be associated with increased susceptibility to trauma- and transfusion-associated acute respiratory distress syndrome (ARDS). We sought to determine 1) the prevalence of cigarette smoke exposure in a diverse multi-center sample of ARDS patients, and 2) whether cigarette smoke exposure is associated with severity of lung injury and mortality in ARDS. Design Analysis of the Albuterol for the Treatment of ALI (ALTA) and Omega ARDS Network studies. Setting Acute Respiratory Distress Syndrome Network hospitals. Patients Three hundred eighty one patients with ARDS. Interventions None. Measurements NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), a validated tobacco-specific marker, was measured in urine samples from subjects enrolled in two NHLBI ARDS Network randomized controlled trials. Main Results Urine NNAL levels were consistent with active smoking in 36% of ARDS patients and with passive smoking in 41% of nonsmokers (vs 20% and 40% in general population, respectively). Patients with NNAL levels in the active smoking range were younger and had a higher prevalence of alcohol misuse, fewer comorbidities, lower severity of illness, and less septic shock at enrollment compared to patients with undetectable NNAL levels. Despite this lower severity of illness, the severity of lung injury did not significantly differ based on biomarker-determined smoking status. Cigarette smoke exposure was not significantly associated with death after adjusting for differences in age, alcohol use, comorbidities, and severity of illness. Conclusions In this first multicenter study of biomarker-determined cigarette smoke exposure in ARDS patients, we found that active cigarette smoke exposure was significantly more prevalent among ARDS patients compared to population averages. Despite their younger age, better overall health, and lower severity of illness, smokers by NNAL had similar severity of lung injury as patients with

  14. Sensitivity of heterozygous α1,6-fucosyltransferase knock-out mice to cigarette smoke-induced emphysema: implication of aberrant transforming growth factor-β signaling and matrix metalloproteinase gene expression.

    PubMed

    Gao, Congxiao; Maeno, Toshitaka; Ota, Fumi; Ueno, Manabu; Korekane, Hiroaki; Takamatsu, Shinji; Shirato, Ken; Matsumoto, Akio; Kobayashi, Satoshi; Yoshida, Keiichi; Kitazume, Shinobu; Ohtsubo, Kazuaki; Betsuyaku, Tomoko; Taniguchi, Naoyuki

    2012-05-11

    We previously demonstrated that a deficiency in core fucosylation caused by the genetic disruption of α1,6-fucosyltransferase (Fut8) leads to lethal abnormalities and the development of emphysematous lesions in the lung by attenuation of TGF-β1 receptor signaling. Herein, we investigated the physiological relevance of core fucosylation in the pathogenesis of emphysema using viable heterozygous knock-out mice (Fut8(+/-)) that were exposed to cigarette smoke (CS). The Fut8(+/-) mice exhibited a marked decrease in FUT8 activity, and matrix metalloproteinase (MMP)-9 activities were elevated in the lung at an early stage of exposure. Emphysema developed after a 3-month CS exposure, accompanied by the recruitment of large numbers of macrophages to the lung. CS exposure substantially and persistently elevated the expression level of Smad7, resulting in a significant reduction of Smad2 phosphorylation (which controls MMP-9 expression) in Fut8(+/-) mice and Fut8-deficient embryonic fibroblast cells. These in vivo and in vitro studies show that impaired core fucosylation enhances the susceptibility to CS and constitutes at least part of the disease process of emphysema, in which TGF-β-Smad signaling is impaired and the MMP-mediated destruction of lung parenchyma is up-regulated.

  15. Acute Phenylalanine/Tyrosine Depletion Reduces Motivation to Smoke Cigarettes Across Stages of Addiction

    PubMed Central

    Venugopalan, Viswanath V; Casey, Kevin F; O'Hara, Caitlin; O'Loughlin, Jennifer; Benkelfat, Chawki; Fellows, Lesley K; Leyton, Marco

    2011-01-01

    The neurobiology of tobacco use is poorly understood, possibly in part because the relevant mechanisms might differ depending on past nicotine exposure and degree of addiction. In the present study we investigated whether these factors might affect the role of dopamine (DA). Using the acute phenylalanine/tyrosine depletion method (APTD), DA synthesis was transiently decreased in three groups of abstinent smokers (n=47): (1) early low-frequency smokers, who had smoked a maximum of five cigarettes per day for less than one year, (2) stable low-frequency smokers smoking at the same level as early low-frequency smokers for at least 3 years, and (3) stable high-frequency smokers, who smoked a minimum of 10 or more cigarettes per day for at least 5 years. Motivation to obtain tobacco was measured using a progressive ratio breakpoint schedule for nicotine-containing and de-nicotinized cigarettes. Compared with a nutritionally balanced control mixture, APTD decreased the self-administration of nicotine-containing cigarettes, and this occurred in all three groups of smokers. The results suggest that DA influenced the willingness to sustain effort for nicotine reward, and this was seen in participants at all three levels of cigarette addiction. In the transition from sporadic to addicted use, the role of DA in the motivation to seek drug may change less than previously proposed. PMID:21775977

  16. Acute one-cigarette smoking decreases ghrelin hormone in saliva: a pilot study.

    PubMed

    Kaabi, Yahia A; Khalifa, Mohiealdeen A

    2014-01-01

    Cigarette smoking is commonly associated with weight loss and mechanisms for these weight changes are still elusive. Ghrelin is a peptide hormone that works in a neuroendocrine fashion to stimulate hunger and the desire for food intake. Ghrelin is also secreted in saliva, probably to enhance food taste. In the current study, we tested the direct impact of acute cigarette smoking on total ghrelin found in saliva. Methods. Blood and saliva samples were collected from 30 healthy nonsmoker male volunteers before and after one-cigarette smoke. Total ghrelin in serum and saliva was measured by ELISA based method. Results. Data showed a statistically significant reduction in salivary ghrelin after smoking (P < 0.0001). In serum, total ghrelin levels were not affected before and after smoking (P = 0.1362). Additionally, positive correlation was observed between serum and salivary ghrelin before smoking (r = 0.4143 and P = 0.0158); however, this correlation was lost after smoking (r = 0.1147 and P = 0.5461). Conclusion. Acute one-cigarette smoking can negatively affect ghrelin levels in saliva that might contribute to the dull food taste in smokers.

  17. Acute One-Cigarette Smoking Decreases Ghrelin Hormone in Saliva: A Pilot Study

    PubMed Central

    Kaabi, Yahia A.; Khalifa, Mohiealdeen A.

    2014-01-01

    Cigarette smoking is commonly associated with weight loss and mechanisms for these weight changes are still elusive. Ghrelin is a peptide hormone that works in a neuroendocrine fashion to stimulate hunger and the desire for food intake. Ghrelin is also secreted in saliva, probably to enhance food taste. In the current study, we tested the direct impact of acute cigarette smoking on total ghrelin found in saliva. Methods. Blood and saliva samples were collected from 30 healthy nonsmoker male volunteers before and after one-cigarette smoke. Total ghrelin in serum and saliva was measured by ELISA based method. Results. Data showed a statistically significant reduction in salivary ghrelin after smoking (P < 0.0001). In serum, total ghrelin levels were not affected before and after smoking (P = 0.1362). Additionally, positive correlation was observed between serum and salivary ghrelin before smoking (r = 0.4143 and P = 0.0158); however, this correlation was lost after smoking (r = 0.1147 and P = 0.5461). Conclusion. Acute one-cigarette smoking can negatively affect ghrelin levels in saliva that might contribute to the dull food taste in smokers. PMID:24808912

  18. Acute effects of caffeine and cigarette smoking on ventricular long-axis function in healthy subjects

    PubMed Central

    Giacomin, Elisa; Palmerini, Elisabetta; Ballo, Piercarlo; Zacà, Valerio; Bova, Giovanni; Mondillo, Sergio

    2008-01-01

    Background Few data exist regarding the direct effects of caffeine and smoking on cardiac function. We sought to explore the acute effects of caffeine assumption, cigarette smoking, or both on left ventricular (LV) and right ventricular (RV) function in a population of young normal subjects. Methods Forty-five healthy subjects aged 25 ± 2 years underwent echocardiography. Fifteen of them were non-smokers and habitual coffee consumers (group 1), 15 were smokers and not habitual coffee consumers (group 2), and 15 were smokers and habitual coffee consumers (group 3). Peak systolic (Sa), early diastolic Ea, and late diastolic (Aa) velocity of mitral annulus were measured by pulsed Tissue Doppler, and left atrioventricular plane displacement was determined by M-mode. Tricuspid annular velocities and systolic excursion (TAPSE) were also determined. Measurements were performed at baseline and after oral assumption of caffeine 100 mg in group 1, one cigarette smoking in group 2, and both in group 3. Results No changes in ventricular function were observed in group 1 after caffeine administration. In group 2, cigarette smoking yielded an acute increase in mitral Aa (+12.1%, p = 0.0026), tricuspid Sa (+9.8%, p = 0.012) and TAPSE (+7.9%, p = 0.017), and a decrease in the mitral Ea/Aa ratio (-8.5%, p = 0.0084). Sequential caffeine assumption and cigarette smoking in group 3 was associated with an acute increase in mitral Aa (+13.0%, p = 0.015) and tricuspid Aa (+11.6%, p < 0.0001) and a reduction in mitral Ea/Aa ratio (-8.5%, p = 0.0084) tricuspid Ea (-6.6%, p = 0.048) and tricuspid Ea/Aa ratio (-9.6%, p = 0.0003). In a two-way ANOVA model controlling for hemodynamic confounding factors, changes in the overall population remained significant for mitral Aa and Ea/Aa ratio, and for tricuspid Aa and Ea/Aa ratio. Conclusion In young healthy subjects, one cigarette smoking is associated to an acute impairment in LV diastolic function and a hyperdynamic RV systolic response

  19. Acute risperidone treatment did not increase daily cigarette consumption or plasma levels of cotinine and caffeine: a pilot study.

    PubMed

    Yoshimura, Reiji; Kakihara, Shingo; Umene-Nakano, Wakako; Sugita, Atsuko; Hori, Hikaru; Ueda, Nobuhisa; Nakamura, Jun

    2008-06-01

    Excessive cigarette smoking and caffeine intake are often seen in schizophrenic patients being treated with antipsychotic drugs, particularly typical antipsychotic drugs. Using nicotine and caffeine sometimes influences psychotic symptoms in these patients. Clozapine is the only antipsychotic drug reported to reduce the amount of cigarette smoking, however, still remains controversial of its efficacy. In the present study, we examined the effect of acute risperidone treatment on the amount of cigarette smoking and plasma levels of cotinine and caffeine in schizophrenic patients. Treatment with risperidone for 4 weeks did not increase daily cigarette consumption or plasma levels of cotinine and caffeine. The results suggest that acute risperidone treatment does not promote the intake of nicotine and caffeine at least by 4 weeks in schizophrenic patients.

  20. Activation of C3a receptor is required in cigarette smoke-mediated emphysema

    PubMed Central

    Yuan, Xiaoyi; Shan, Ming; You, Ran; Frazier, Michael V.; Hong, Monica Jeongsoo; Wetsel, Rick A.; Drouin, Scott; Seryshev, Alexander; MD, Li-zhen Song; Cornwell, Lorraine; Rossen, Roger D; Corry, David B.; Kheradmand, Farrah

    2014-01-01

    Exposure to cigarette smoke can initiate sterile inflammatory responses in the lung and activate myeloid dendritic cells (mDCs) that induce differentiation of T helper type 1 (Th1) and Th17 cells in the emphysematous lungs. Consumption of complement proteins increases in acute inflammation, but the contribution of complement protein 3 (C3) to chronic cigarette smoke-induced immune responses in the lung is not clear. Here we show that following chronic exposure to cigarette smoke, C3 deficient (C3−/−) mice develop less emphysema and have fewer CD11b+CD11c+ mDCs infiltrating the lungs as compared to wild type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases expression of its receptor (C3aR) on lung mDCs. Mice deficient in the C3aR (C3ar−/−) partially phenocopy the attenuated responses to chronic smoke observed in C3−/− mice. Consistent with a role for C3 in emphysema C3 and its active fragments are deposited on the lung tissue of smokers with emphysema, and smoke exposed mice. Together, these findings suggest a critical role for C3a through autocrine/paracrine induction of C3aR in the pathogenesis of cigarette smoke induced sterile inflammation and provide new therapeutic targets for the treatment of emphysema. PMID:25465103

  1. Effects of cigarette smoking on metabolic events in the lung

    SciTech Connect

    Kitamura, S.

    1987-06-01

    Nicotine and cigarette smoke extract show acute physiological effects: increasing tracheal pressure (P/sub TR/), pulmonary artery pressure (P/sub PA/), systemic blood pressure (P/sub SYST/), and left atrium pressure (P/sub LA/); and decreasing cardiac output (Q/sub AORTA/) and blood flow to the left lower lobe (Q/sub LLL/). In addition, cigarette smoking induces bronchoconstriction, thus decreasing peak flow, FVC, and FEV/sub 1.0/ in healthy subjects. It has also been demonstrated that cigarette smoking caused temporary slowing of mucociliary clearance in the lung and that cigarette smoke increases the activity of aryl hydrocarbon hydroxylase which metabolizes benzo(..cap alpha..)pyrene. The authors demonstrated that serum angiotensin I converting enzyme (ACE) activity showed a significant increase immediately after smoking and returned to the control level 20 min after smoking. They also demonstrated that plasma histamine levels showed a marked decrease after smoking. Furthermore, the effects of cigarette smoke and related substances on prostaglandin, thromboxane, testosterone, cyclic nucleotides metabolism, and protein synthesis were also investigated.

  2. HDAC3 mediates smoking-induced pancreatic cancer

    PubMed Central

    Edderkaoui, Mouad; Xu, Shiping; Chheda, Chintan; Morvaridi, Susan; Hu, Robert W.; Grippo, Paul J.; Mascariñas, Emman; Principe, Daniel R.; Knudsen, Beatrice; Xue, Jing; Habtezion, Aida; Uyeminami, Dale; Pinkerton, Kent E.; Pandol, Stephen J.

    2016-01-01

    Smoking is a major risk factor for developing pancreatic adenocarcinoma (PDAC); however, little is known about the mechanisms involved. Here we employed a genetic animal model of early stages of PDAC that overexpresses oncogenic Kras in the pancreas to investigate the mechanisms of smoking-induced promotion of the disease in vivo. We confirmed the regulation of the interactions between the tumor microenvironment cells using in vitro cellular systems. Aerial exposure to cigarette smoke stimulated development of pancreatic intraepithelial neaoplasia (PanIN) lesions associated with a tumor microenvironment-containing features of human PDAC including fibrosis, activated stellate cells, M2-macrophages and markers of epithelial-mesenchymal transition (EMT). The pro-cancer effects of smoking were prevented by Histone Deacetylase HDAC I/II inhibitor Saha. Smoking decreased histone acetylation associated with recruitment of and phenotypic changes in macrophages; which in turn, stimulated survival and induction of EMT of the pre-cancer and cancer cells. The interaction between the cancer cells and macrophages is mediated by IL-6 produced under the regulation of HDAC3 translocation to the nucleus in the cancer cells. Pharmacological and molecular inhibitions of HDAC3 decreased IL-6 levels in cancer cells. IL-6 stimulated the macrophage phenotype change through regulation of the IL-4 receptor level of the macrophage. This study demonstrates a novel pathway of interaction between cancer cells and tumor promoting macrophages involving HDAC3 and IL-6. It further demonstrates that targeting HDAC3 prevents progression of the disease and could provide a strategy for treating the disease considering that the HDAC inhibitor we used is FDA approved for a different disease. PMID:26745602

  3. Acute fatal pericardial effusion induced by accidental ingestion of cigarette butts in a dog

    PubMed Central

    Kim, Jung-Hyun; Lim, Jae-Hyun

    2016-01-01

    A dog was referred for collapse and tachypnea after ingesting cigarette butts. Thoracic radiography and echocardiography indicated pericardial effusion, and an electrocardiogram showed tachycardia, variable QRS complexes, and ventricular premature complexes. This is the first description of fatal pericardial effusion associated with cigarette butt ingestion in a veterinary patient. PMID:26834265

  4. Electronic Cigarettes

    MedlinePlus

    ... New FDA Regulations Text Size: A A A Electronic Cigarettes Electronic cigarettes (e-cigarettes) are battery operated products designed ... more about: The latest news and events about electronic cigarettes on this FDA page Electronic cigarette basics ...

  5. Scrambled and fried: Cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress

    SciTech Connect

    Sobinoff, A.P.; Beckett, E.L.; Jarnicki, A.G.; Sutherland, J.M.; McCluskey, A.; Hansbro, P.M.; McLaughlin, E.A.

    2013-09-01

    Cigarette smoke is a reproductive hazard associated with pre-mature reproductive senescence and reduced clinical pregnancy rates in female smokers. Despite an increased awareness of the adverse effects of cigarette smoke exposure on systemic health, many women remain unaware of the adverse effects of cigarette smoke on female fertility. This issue is compounded by our limited understanding of the molecular mechanisms behind cigarette smoke induced infertility. In this study we used a direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease to characterise mechanisms of cigarette-smoke induced ovotoxicity. Cigarette smoke exposure caused increased levels of primordial follicle depletion, antral follicle oocyte apoptosis and oxidative stress in exposed ovaries, resulting in fewer follicles available for ovulation. Evidence of oxidative stress also persisted in ovulated oocytes which escaped destruction, with increased levels of mitochondrial ROS and lipid peroxidation resulting in reduced fertilisation potential. Microarray analysis of ovarian tissue correlated these insults with a complex mechanism of ovotoxicity involving genes associated with detoxification, inflammation, follicular activation, immune cell mediated apoptosis and membrane organisation. In particular, the phase I detoxifying enzyme cyp2e1 was found to be significantly up-regulated in developing oocytes; an enzyme known to cause molecular bioactivation resulting in oxidative stress. Our results provide a preliminary model of cigarette smoke induced sub-fertility through cyp2e1 bioactivation and oxidative stress, resulting in developing follicle depletion and oocyte dysfunction. - Highlights: • Cigarette smoke exposure targets developing follicle oocytes. • The antral follicle oocyte is a primary site of ovarian cigarette smoke metabolism. • Cyp2e1 is a major enzyme involved in ameliorating smoke-induced ovotoxicity. • Cigarette smoke causes oocyte

  6. Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking.

    PubMed

    Rose, J E; Behm, F M; Westman, E C

    2001-02-01

    Separate and combined effects of nicotine and the nicotinic antagonist mecamylamine were studied in 32 healthy volunteer smokers after overnight abstinence from smoking. Subjects participated in three sessions (3 h each), during which they wore skin patches delivering either 0 mg/24 h, 21 mg/24 h or 42 mg/24 h nicotine. Thirty-two subjects were randomly assigned to two groups receiving oral mecamylamine hydrochloride (10 mg) vs. placebo capsules. Two and one-half hours after drug administration, subjects were allowed to smoke ad lib, rating the cigarettes for rewarding and aversive effects. Transdermal nicotine produced a dose-related reduction in the subjective rewarding qualities of smoking. Nicotine also reduced craving for cigarettes and this effect was attenuated, but not eliminated, by mecamylamine. Mecamylamine blocked the discriminability of high vs. low nicotine puffs of smoke, and increased nicotine intake substantially during the ad lib smoking period. Some of the psychophysiological effects of each drug (elevation in blood pressure from nicotine, sedation and decreased blood pressure from mecamylamine) were offset by the other drug. The results supported the hypothesis that nicotine replacement can alleviate tobacco withdrawal symptoms even in the presence of an antagonist such as mecamylamine. Mecamylamine did not precipitate withdrawal beyond the level associated with overnight cigarette deprivation, suggesting its effects were primarily due to offsetting the action of concurrently administered nicotine as opposed to blocking endogenous cholinergic transmission.

  7. Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium

    PubMed Central

    Sridhar, Sriram; Schembri, Frank; Zeskind, Julie; Shah, Vishal; Gustafson, Adam M; Steiling, Katrina; Liu, Gang; Dumas, Yves-Martine; Zhang, Xiaohui; Brody, Jerome S; Lenburg, Marc E; Spira, Avrum

    2008-01-01

    Background Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers. Results Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome"), we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure. Conclusion Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for tobacco exposure as well as a

  8. A single blueberry (Vaccinium corymbosum) portion does not affect markers of antioxidant defence and oxidative stress in healthy volunteers following cigarette smoking.

    PubMed

    Del Bo', Cristian; Porrini, Marisa; Campolo, Jonica; Parolini, Marina; Lanti, Claudia; Klimis-Zacas, Dorothy; Riso, Patrizia

    2016-03-01

    We previously reported that a portion of blueberries reversed endothelial dysfunction induced by acute cigarette smoking. Since smoking-induced endothelial dysfunction is associated with a condition of oxidative stress, we evaluated whether the observed effect was mediated by modulation of markers of oxidative stress and antioxidant defence. Fourteen out of 16 male healthy smokers previously enrolled, participated in a three-armed randomized controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300g of blueberries) + smoking (one cigarette); control treatment (300ml of water with sugar) + smoking (one cigarette). The cigarette was smoked 100min after blueberry/control/water consumption. Each treatment was separated by 1 week of washout period. Plasma vitamin (C, B12 and folate) and aminothiol concentrations, endogenous [formamidopyrimidine-DNA glycosylase (FPG)-sensitive sites] and oxidatively induced DNA damage (resistance to H2O2-induced DNA damage) in peripheral blood mononuclear cells (PBMCs) were measured at baseline and 20, 60, 90, 120min and 24h after smoking. On the whole, analysis of variance did not show a significant effect of treatment on the modulation of markers of oxidative stress and antioxidant defence but revealed an effect of time for plasma concentrations of vitamin C (P = 0.003), B12 (P < 0.001), folate (P < 0.001), total cysteine (P = 0.007) and cysteine-glycine (P = 0.010) that increased following the three treatments after smoking. No significant effect of treatment was observed for the levels of FPG-sensitive sites (P > 0.05) and H2O2-induced DNA damage (P > 0.05) in PBMCs. In conclusion, the consumption of a single blueberry portion failed to modulate markers of oxidative stress and antioxidant defence investigated in our experimental conditions. Further studies are necessary to elucidate this finding and help clarifying the mechanisms of protection of blueberries against

  9. Effects of acute and chronic cigarette smoking on the expression of endothelin-1 mRNA of the cardiovascular tissues in rats.

    PubMed

    Adachi, C; Naruse, M; Ishihara, Y; Tanabe, A; Takagi, S; Yoshimoto, T; Naruse, K; Kagawa, J; Takano, K

    2000-11-01

    Although smoking has been suggested to be involved in the development of cardiovascular diseases, details of the mechanism still need to be revealed. We investigated the effects of cigarette smoking on the tissue mRNA expression of endothelin-1 (ET-1). Male Wistar rats of 4 weeks of age were exposed to smoke from six cigarettes for 30 min (acute exposure) and six cigarettes for 30 min/day, 5 days a week for 6 months (chronic exposure). Half of the rats exposed to 6 months smoking were kept in clean-air conditions for a further 3 months to clear the effects. Tissue expression of ET-1 mRNA in the kidney, aorta, heart and lung was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. There was no significant difference in body and organ weight of the heart and kidney between the control and smoking group in either the acute or chronic experiment. In the acute-exposure experiment, expression of ET-1 mRNA was increased in the heart and lung, while that in the kidney and aorta was unchanged. In the chronic-exposure experiment, however, there was no significant difference in the expression of ET-1 mRNA in all the tissues between the smoking and control groups. These results suggest that cigarette smoking could cause cardiovascular and pulmonary diseases by modulating ET-1 mRNA expression in the tissues.

  10. Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen

    SciTech Connect

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Magarelli, J.L.; Bruck, D.C.

    1987-01-01

    We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in /sup 99m/TcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits.

  11. Acute systemic accumulation of acrolein in mice by inhalation at a concentration similar to that in cigarette smoke

    PubMed Central

    Tully, Melissa; Zheng, Lingxing; Acosta, Glen; Tian, Ran; Shi, Riyi

    2015-01-01

    Cigarette smoke is an important environmental factor associated with a wide array of public health concerns. Acrolein, a component of tobacco smoke and a known toxin to various cell types, may be a key pathological factor mediating the adverse effects linked with tobacco smoke. Although acrolein is known to accumulate in the respiratory system after acute nasal exposure, it is not clear if it accumulates systemically, and less is known in the nervous system. The aim of this study was to assess the degree of acrolein accumulation in the circulation and in the spinal cord following acute acrolein inhalation in mice. Using a laboratory-fabricated inhalation chamber, we found elevated urinary 3-HPMA, an acrolein metabolite, and increased acrolein adducts in the spinal cord after weeks of nasal exposure to acrolein at a concentration similar to that in tobacco smoke. The data indicated that acrolein is absorbed into the circulatory system and some enters the nervous system. It is expected that these findings may facilitate further studies to probe the pathological role of acrolein in the nervous system resulting from smoke and other external sources. PMID:25446876

  12. Gene Profiles in a Smoke-Induced COPD Mouse Lung Model Following Treatment with Mesenchymal Stem Cells.

    PubMed

    Kim, You-Sun; Kokturk, Nurdan; Kim, Ji-Young; Lee, Sei Won; Lim, Jaeyun; Choi, Soo Jin; Oh, Wonil; Oh, Yeon-Mok

    2016-10-01

    Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models. The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously. In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs. Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs). Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs. Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection. The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14. A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs. Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection. These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke. These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD.

  13. Gene Profiles in a Smoke-Induced COPD Mouse Lung Model Following Treatment with Mesenchymal Stem Cells

    PubMed Central

    Kim, You-Sun; Kokturk, Nurdan; Kim, Ji-Young; Lee, Sei Won; Lim, Jaeyun; Choi, Soo Jin; Oh, Wonil; Oh, Yeon-Mok

    2016-01-01

    Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models. The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously. In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs. Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs). Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs. Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection. The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14. A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs. Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection. These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke. These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD. PMID:27802588

  14. Intratracheal transplantation of endothelial progenitor cells attenuates smoking-induced COPD in mice

    PubMed Central

    Shi, Zhihui; Chen, Yan; Cao, Jun; Zeng, Huihui; Yang, Yue; Chen, Ping; Luo, Hong; Peng, Hong; Cai, Shan; Guan, Chaxiang

    2017-01-01

    Background Endothelial progenitor cells (EPCs) might play a protective role in COPD. The aim of this study was to investigate whether intratracheal allogeneic transplantation of bone-marrow-derived EPCs would attenuate the development of smoking-induced COPD in mice. Methods Isolated mononuclear cells from the bone marrow of C57BL/6J mice were cultured in endothelial cell growth medium-2 for 10 days, yielding EPCs. A murine model of COPD was established by passive 90-day exposure of cigarette smoke. On day 30, EPCs or phosphate-buffered saline alone was administered into the trachea. On day 90, EPCs or 30 μL phosphate-buffered saline alone was administered into the trachea, and on day 120, inflammatory cells, antioxidant activity, apoptosis, matrix metalloproteinase (MMP)-2, and MMP-9 were measured. Results After EPC treatment, the lung function of the mice had improved compared with the untreated mice. Mean linear intercept and destructive index were reduced in the EPCs-treated group compared with the untreated group. In addition, the EPCs-treated mice exhibited less antioxidant activity in bronchoalveolar lavage fluid compared with the untreated mice. Moreover, decreased activities of MMP-2, MMP-9, and TUNEL-positive cells in lung tissues were detected in EPCs-treated mice. Conclusion Intratracheal transplantation of EPCs attenuated the development of pulmonary emphysema and lung function disorder probably by alleviating inflammatory infiltration, decelerating apoptosis, inhibiting proteolytic enzyme activity, and improving antioxidant activity. PMID:28360519

  15. Heme oxygenase-1 attenuates inflammation and oxidative damage in a rat model of smoke-induced emphysema.

    PubMed

    Wei, Jingjing; Fan, Guoquan; Zhao, Hui; Li, Jianqiang

    2015-11-01

    Emphysema is a serious disease of the respiratory system and is associated with inflammation and oxidative stress. Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in heme biosynthesis, exerts potent anti-inflammatory, antioxidant, anti-apoptotic and anti‑proliferative effects in various diseases. In the present study, we examined the effects of HO-1 on smoke‑induced emphysema, as well as the underlying mechanisms in a rat model of smoke-induced emphysema. Rats were either exposed to cigarette smoke or sham‑exposed for 20 weeks to establish the model of smoke-induced emphysema. The rats were subcutaneously injected with protoporphyrin IX [tin-protoporphyrin IX (SnPP) or ferriprotoporphyrin IX chloride (hemin)] during this period to examine the protective effects of HO-1. Subsequently, the development of emphysema, inflammatory cells, the levels of inflammatory mediators, particularly interleukin (IL)-17, tumor necrosis factor (TNF)‑α, monocyte chemotactic protein‑1 [MCP‑1, also known as chemokine (C-C motif) ligand 2 (CCL2)], IL-8 [also known as chemokine (C-X-C motif) ligand 8 (CXCL8)], macrophage inflammatory protein‑2α [MIP-2α, also known as chemokine (C-X-C motif) ligand 2 (CXCL2)] and IL-10, as well as the malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) content were determined. Exposure to smoke increased the total cell, neutrophil and macrophage counts in the bronchoalveolar lavage fluid (BALF). It also increased the levels of the inflammatory mediators, IL-17, TNF-α, MCP-1, IL-8 and MIP-2α, as well as the MDA content and induced emphysema. Treatment with hemin upregulated HO-1 expression and attenuated the development of smoke-induced emphysema by reducing inflammatory cell infiltration, decreasing the levels of inflammatory mediators and attenuating oxidative damage, to a certain extent. In conclusion, our findings demonstrate that HO-1 exerts anti-inflammatory and antioxidant effects, thus attenuating the

  16. Cigarette Smoke-Induced Interleukin-1 Alpha May Be Involved in the Pathogenesis of Adult Acne

    PubMed Central

    Yang, Yun Seok; Lim, Hee Kyeong; Hong, Kyung Kook; Shin, Min Kyung; Lee, Jin Woo; Lee, Sung Won

    2014-01-01

    Background Lipid peroxide (LPO) in comedones, which are produced as a result of sebum oxidation, might potentially induce interleukin-1α (IL-1α) and exacerbate comedogenesis and inflammatory changes in comedones. Objective To investigate the relationship of proinflammatory cytokines and LPO levels in the extracts of comedones with the acne of clinical difference between smokers and non-smokers, and with the severity and distribution of the acne lesions. Methods Twenty-two non-smoking and 21 smoking adult acne patients were evaluated by comedone extraction and measurement of proinflammatory cytokines and LPO levels. Acne severity and distribution of the lesions were also analyzed. Results Relative to the non-smoking group, smokers had significantly higher levels of IL-1α and LPO in comedones. Their levels showed a positive correlation. However, there were no statistically significant difference between the severity or distribution of the disease and the levels of LPO and IL-1α in comedones. Conclusion Smoking may be involved in the pathogenesis of adult acne by increasing the oxidative stress that results in subsequent accumulation of LPO in comedones. PMID:24648681

  17. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke–Induced COPD in C57BL/6 mice

    PubMed Central

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; Ligeiro de Oliveira, Ana Paula

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J—660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

  18. Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer.

    PubMed

    Shaykhiev, Renat; Sackrowitz, Rachel; Fukui, Tomoya; Zuo, Wu-Lin; Chao, Ion Wa; Strulovici-Barel, Yael; Downey, Robert J; Crystal, Ronald G

    2013-09-01

    CXCL14, a recently described epithelial cytokine, plays putative multiple roles in inflammation and carcinogenesis. In the context that chronic obstructive pulmonary disease (COPD) and lung cancer are both smoking-related disorders associated with airway epithelial disorder and inflammation, we hypothesized that the airway epithelium responds to cigarette smoking with altered CXCL14 gene expression, contributing to the disease-relevant phenotype. Using genome-wide microarrays with subsequent immunohistochemical analysis, the data demonstrate that the expression of CXCL14 is up-regulated in the airway epithelium of healthy smokers and further increased in COPD smokers, especially within hyperplastic/metaplastic lesions, in association with multiple genes relevant to epithelial structural integrity and cancer. In vitro experiments revealed that the expression of CXCL14 is induced in the differentiated airway epithelium by cigarette smoke extract, and that epidermal growth factor mediates CXCL14 up-regulation in the airway epithelium through its effects on the basal stem/progenitor cell population. Analyses of two independent lung cancer cohorts revealed a dramatic up-regulation of CXCL14 expression in adenocarcinoma and squamous-cell carcinoma. High expression of the COPD-associated CXCL14-correlating cluster of genes was linked in lung adenocarcinoma with poor survival. These data suggest that the smoking-induced expression of CXCL14 in the airway epithelium represents a novel potential molecular link between smoking-associated airway epithelial injury, COPD, and lung cancer.

  19. Waterpipe smoking induces epigenetic changes in the small airway epithelium.

    PubMed

    Walters, Matthew S; Salit, Jacqueline; Ju, Jin Hyun; Staudt, Michelle R; Kaner, Robert J; Rogalski, Allison M; Sodeinde, Teniola B; Rahim, Riyaad; Strulovici-Barel, Yael; Mezey, Jason G; Almulla, Ahmad M; Sattar, Hisham; Mahmoud, Mai; Crystal, Ronald G

    2017-01-01

    Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use waterpipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.

  20. Waterpipe smoking induces epigenetic changes in the small airway epithelium

    PubMed Central

    Ju, Jin Hyun; Staudt, Michelle R.; Kaner, Robert J.; Rogalski, Allison M.; Sodeinde, Teniola B.; Rahim, Riyaad; Strulovici-Barel, Yael; Mezey, Jason G.; Almulla, Ahmad M.; Sattar, Hisham; Mahmoud, Mai; Crystal, Ronald G.

    2017-01-01

    Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use waterpipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking. PMID:28273093

  1. Smoke-induced seed germination in California chaparral

    USGS Publications Warehouse

    Keeley, J.E.; Fotheringham, C.J.

    1998-01-01

    The California chaparral community has a rich flora of species with different mechanisms for cuing germination to postfire conditions. Heat shock triggers germination of certain species but has no stimulatory effect on a great many other postfire species that are chemically stimulated by combustion products. Previous reports have shown that charred wood will induce germination, and here we report that smoke also induces germination in these same species. Smoke is highly effective, often inducing 100% germination in deeply dormant seed populations with 0% control germination. Smoke induces germination both directly and indirectly by aqueous or gaseous transfer from soil to seeds. Neither nitrate nor ammonium ions were effective in stimulating germination of smoke-stimulated species, nor were most of the quantitatively important gases generated by biomass smoke. Nitrogen dioxide, however, was very effective at inducing germination in Caulanthus heterophyllus (Brassicaceae), Emmenanthe penduliflora (Hydrophyllaceae), Phacelia grandiflora (Hydrophyllaceae), and Silene multinervia (Caryophyllaceae). Three species, Dendromecon rigida (Papaveraceae), Dicentra chrysantha, and Trichostema lanatum (Lamiaceae), failed to germinate unless smoke treatment was coupled with prior treatment of 1 yr soil storage. Smoke-stimulated germination was found in 25 chaparral species, representing 11 families, none of which were families known for heat-shock-stimulated germination. Seeds of smoke-stimulated species have many analogous characteristics that separate them from most heat-shock-stimulated seeds, including: (1) outer seed coats that are highly textured, (2) a poorly developed outer cuticle, (3) absence of a dense palisade tissue in the seed coat, and (4) a subdermal membrane that is semipermeable, allowing water passage but blocking entry of large (molecular mass > 500) solutes. Tentative evidence suggests that permeability characteristics of this subdermal layer are altered by

  2. Cigarette smoke metabolically promotes cancer, via autophagy and premature aging in the host stromal microenvironment

    PubMed Central

    Salem, Ahmed F.; Al-Zoubi, Mazhar Salim; Whitaker-Menezes, Diana; Martinez-Outschoorn, Ubaldo E.; Lamb, Rebecca; Hulit, James; Howell, Anthony; Gandara, Ricardo; Sartini, Marina; Galbiati, Ferruccio; Bevilacqua, Generoso; Sotgia, Federica; Lisanti, Michael P.

    2013-01-01

    Cigarette smoke has been directly implicated in the disease pathogenesis of a plethora of different human cancer subtypes, including breast cancers. The prevailing view is that cigarette smoke acts as a mutagen and DNA damaging agent in normal epithelial cells, driving tumor initiation. However, its potential negative metabolic effects on the normal stromal microenvironment have been largely ignored. Here, we propose a new mechanism by which carcinogen-rich cigarette smoke may promote cancer growth, by metabolically “fertilizing” the host microenvironment. More specifically, we show that cigarette smoke exposure is indeed sufficient to drive the onset of the cancer-associated fibroblast phenotype via the induction of DNA damage, autophagy and mitophagy in the tumor stroma. In turn, cigarette smoke exposure induces premature aging and mitochondrial dysfunction in stromal fibroblasts, leading to the secretion of high-energy mitochondrial fuels, such as L-lactate and ketone bodies. Hence, cigarette smoke induces catabolism in the local microenvironment, directly fueling oxidative mitochondrial metabolism (OXPHOS) in neighboring epithelial cancer cells, actively promoting anabolic tumor growth. Remarkably, these autophagic-senescent fibroblasts increased breast cancer tumor growth in vivo by up to 4-fold. Importantly, we show that cigarette smoke-induced metabolic reprogramming of the fibroblastic stroma occurs independently of tumor neo-angiogenesis. We discuss the possible implications of our current findings for the prevention of aging-associated human diseases and, especially, common epithelial cancers, as we show that cigarette smoke can systemically accelerate aging in the host microenvironment. Finally, our current findings are consistent with the idea that cigarette smoke induces the “reverse Warburg effect,” thereby fueling “two-compartment tumor metabolism” and oxidative mitochondrial metabolism in epithelial cancer cells. PMID:23388463

  3. Antibacterial Defense of Human Airway Epithelial Cells from Chronic Obstructive Pulmonary Disease Patients Induced by Acute Exposure to Nontypeable Haemophilus influenzae: Modulation by Cigarette Smoke.

    PubMed

    Amatngalim, Gimano D; Schrumpf, Jasmijn A; Henic, Almira; Dronkers, Esther; Verhoosel, Renate M; Ordonez, Soledad R; Haagsman, Henk P; Fuentes, Maria E; Sridhar, Sriram; Aarbiou, Jamil; Janssen, Richard A J; Lekkerkerker, Annemarie N; Hiemstra, Pieter S

    2017-02-08

    Antimicrobial proteins and peptides (AMPs) are a central component of the antibacterial activity of airway epithelial cells. It has been proposed that a decrease in antibacterial lung defense contributes to an increased susceptibility to microbial infection in smokers and patients with chronic obstructive pulmonary disease (COPD). However, whether reduced AMP expression in the epithelium contributes to this lower defense is largely unknown. We investigated the bacterial killing activity and expression of AMPs by air-liquid interface-cultured primary bronchial epithelial cells from COPD patients and non-COPD (ex-)smokers that were stimulated with nontypeable Haemophilus influenzae (NTHi). In addition, the effect of cigarette smoke on AMP expression and the activation of signaling pathways was determined. COPD cell cultures displayed reduced antibacterial activity, whereas smoke exposure suppressed the NTHi-induced expression of AMPs and further increased IL-8 expression in COPD and non-COPD cultures. Moreover, smoke exposure impaired NTHi-induced activation of NF-κB, but not MAP-kinase signaling. Our findings demonstrate that the antibacterial activity of cultured airway epithelial cells induced by acute bacterial exposure was reduced in COPD and suppressed by cigarette smoke, whereas inflammatory responses persisted. These findings help to explain the imbalance between protective antibacterial and destructive inflammatory innate immune responses in COPD.

  4. Cigarette smoke activates human monocytes by an oxidant-AP-1 signaling pathway: implications for steroid resistance.

    PubMed

    Walters, Matthew J; Paul-Clark, Mark J; McMaster, Shaun K; Ito, Kazuhiro; Adcock, Ian M; Mitchell, Jane A

    2005-11-01

    Smoking cigarettes is a major risk factor for the development of cardiovascular and respiratory disease. Moreover, smoking-induced pathophysiology is often resistant to the anti-inflammatory effects of glucocorticoids. The nature of cigarette smoke-induced inflammation is still not defined, although neutrophil recruitment and activation seem to be consistent features. In the current study, we have used a range of approaches to demonstrate that cigarette smoke activates human monocytes and macrophages to release the CXC chemokine CXCL8 [(interleukin-8 (IL-8)]. Furthermore, we show for the first time that cigarette smoke synergizes with proinflammatory cytokines IL-1beta and tumor necrosis factor-alpha, and it is this interaction that confers steroid resistance to smoke-induced CXCL8 release. We go on to show that smoke-induced activation of human cells is an oxidant-mediated phenomenon acting through activator protein-1, but not nuclear factor kappaB, pathway. These observations add significantly to our understanding of smoke as an inflammatory stimulus that has implications for potential the development of treatments of smoking or related disease.

  5. The changing cigarette, 1950-1995.

    PubMed

    Hoffmann, D; Hoffmann, I

    1997-03-01

    Nicotine is recognized to be the major inducer of tobacco dependence. The smoking of cigarettes as an advantageous delivery system for nicotine, accelerates and aggravates cardiovascular disease, and is causally associated with increased risks for chronic obstructive lung disease, cancer of the lung and of the upper aerodigestive system, and cancer of the pancreas, renal pelvis, and urinary bladder. It is also associated with cancer of the liver, cancer of the uterine cervix, cancer of the nasal cavity, and myeloid leukemia. In 1950, the first large-scale epidemiological studies documented that cigarette smoking induces lung cancer and described a dose-response relationship between number of cigarettes smoked and the risk for developing lung cancer. In the following decades these observations were not only confirmed by several hundreds of prospective and case-control studies but the plausibility of this causal association was also supported by bioassays and by the identification of carcinogens in cigarette smoke. Whole smoke induces lung tumors in mice and tumors in the upper respiratory tract of hamsters. The particulate matter of the smoke elicits benign and malignant tumors on the skin of mice and rabbits, sarcoma in the connective tissue of rats, and carcinoma in the lungs of rats upon intratracheal instillation. More than 50 carcinogens have been identified, including the following classes of compounds: polynuclear aromatic hydrocarbons (PAH), aromatic amines, and N-nitrosamines. Among the latter, the tobacco-specific N-nitrosamines (TSNA) have been shown to be of special significance. Since 1950, the makeup of cigarettes and the composition of cigarette smoke have gradually changed. In the United States, the sales-weighted average "tar" and nicotine yields have declined from a high of 38 mg "tar" and 2.7 mg nicotine in 1954 to 12 mg and 0.95 mg in 1992, respectively. In the United Kingdom, the decline was from about 32 mg "tar" and 2.2 mg nicotine to less

  6. Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach

    PubMed Central

    Ross, Clare L; Galloway-Phillipps, Neil; Armstrong, Paul C; Mitchell, Jane A; Warner, Timothy D; Brearley, Christopher; Ito, Mari; Tunstall, Tanushree; Elkin, Sarah; Kon, Onn Min; Hansel, Trevor T; Paul-Clark, Mark J

    2015-01-01

    Introduction Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. Methods and analysis Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. Implications Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. Ethics and dissemination This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals

  7. Comparative 13-week inhalation study of cigarette smoke from cigarettes containing cast sheet tobacco.

    PubMed

    Potts, Ryan J; Meckley, Daniel R; Shreve, W Keith; Pence, Deborah H; Ayres, Paul H; Doolittle, David; Swauger, James E; Sagartz, John W

    2007-06-01

    A subchronic, nose-only inhalation study was conducted to compare the effects of mainstream smoke from a reference cigarette containing conventional reconstituted tobacco sheet at 30% of the finished blend to mainstream smoke from cigarettes containing 10% or 15% cast sheet (a specific type of reconstituted tobacco sheet) substituted for part of the conventional reconstituted tobacco. Male and female Sprague-Dawley rats were exposed for 1 h/day, 5 d/wk, for 13 wk to mainstream smoke at 0, 0.06, 0.20, or 0.80 mg wet total particulate matter per liter of air. Clinical signs, body and organ weights, clinical chemistry, hematology, carboxyhemoglobin (COHb), serum nicotine, plethysmography, gross pathology, and histopathology were determined. Exposure to cigarette smoke induced a number of changes in respiratory physiology, histopathology, and serum nicotine and COHb levels when compared to sham animals. When corresponding dose groups of reference and cast sheet mainstream smokes were compared, no biological differences were noted. At the end of the exposure period, subsets of rats from each group were maintained without smoke exposures for an additional 13 wk (recovery period). At the end of the recovery period, there were no statistically significant differences in histopathological findings observed between the reference and either cast sheet cigarette. Substitution of 10% or 15% cast sheet tobacco for conventional reconstituted tobacco sheet does not alter the inhalation toxicology of the mainstream smoke when compared to mainstream smoke from a reference cigarette containing conventional reconstituted tobacco sheet.

  8. Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

    PubMed

    Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

    2014-04-01

    Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

  9. Cigarette smoking and acute myocardial infarction. A case-control study from the GISSI-2 trial. GISSI-EFRIM Investigators. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto--Epidemiologia dei Fattori di Rischio dell'infarto Miocardioco.

    PubMed

    Negri, E; La Vecchia, C; Nobili, A; D'Avanzo, B; Bechi, S

    1994-08-01

    To make a further quantitative assessment of the relationship between cigarette smoking and the risk of myocardial infarction, a multicentric case-control study was conducted in Italy between September 1988 and June 1989 within the framework of the GISSI-2 trial. Ninety hospitals in various Italian Regions participated. 916 cases of acute myocardial infarction with no history of ischaemic heart disease and 1106 controls admitted to hospital for acute conditions not related to known or suspected risk factors for ischaemic heart disease were studied. Relative risks (RR) and 95% confidence intervals (CI) of myocardial infarction according to various measures of tobacco smoking, were adjusted for identified potential confounding factors using multiple logistic regression. Compared to lifelong non-smokers, the RR was 1.3 (95% CI 1.0 to 1.9) for ex-smokers, 2.0 (95% CI 1.4 to 2.9) for current smokers of less than 15 cigarettes per day, 3.1 (95% CI 2.2 to 4.2) for 15-24 cigarettes per day and 4.9 (95% CI 3.4 to 7.1) for 25 or more cigarettes per day. No trend in risk was evident for the duration, the RR being around 3 for subsequent categories. There was a significant interaction between smoking and age. Below the age 45, smokers of 25 or more cigarettes per day had a 33 times higher risk than non-smokers, compared to 7.5 at in the age group 45-54, 4.4 between the ages 55-64 and 2.5 at the age of 65 or over. The risk estimates were higher in women (RR for > or = 25 cigarettes per day = 10.1), in subjects in the lowest cholesterol tertile (RR = 11.9), with no history of diabetes (RR = 6.8), hypertension (RR = 9.5), no family history ischaemic heart disease (RR = 9.1) and low body mass index (RR = 9.3). The importance of smoking is confirmed as a cause of acute myocardial infarction: about 50% of all nonfatal infarctions in this Italian population could be attributable to cigarette smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. RelB attenuates cigarette smoke extract-induced apoptosis in association with transcriptional regulation of the aryl hydrocarbon receptor.

    PubMed

    Iu, Matthew; Zago, Michela; de Souza, Angela Rico; Bouttier, Manuella; Pareek, Swati; White, John H; Hamid, Qutayba; Eidelman, David H; Baglole, Carolyn J

    2017-02-27

    Chronic obstructive pulmonary disease (COPD) is a chronic and prevalent respiratory disease caused primarily by long term inhalation of cigarette smoke. A major hallmark of COPD is elevated apoptosis of structural lung cells including fibroblasts. The NF-κB member RelB may suppress apoptosis in response to cigarette smoke, but its role in lung cell survival is not known. RelB may act as a pro-survival factor by controlling the expression of superoxide dismutase 2 (SOD2). SOD2 is also regulated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that suppresses cigarette smoke-induced apoptosis. As the AhR is also a binding partner for RelB, we speculate that RelB suppresses cigarette smoke-induced apoptosis by regulating the AhR. Using an in vitro model of cigarette smoke exposure (cigarette smoke extract [CSE]), we found that CSE down-regulated RelB expression in mouse lung fibroblasts, which was associated with elevated levels of cleaved PARP. Genetic ablation of RelB elevated CSE-induced apoptosis, including chromatin condensation, and reduced mitochondrial function. There was also more reactive oxygen species production in RelB(-/-) cells exposed to CSE. While there was no alteration in Nrf2 expression or localization between RelB(-/-) and wild type cells in response to CSE, RelB(-/-) cells displayed significantly decreased AhR mRNA and protein expression, concomitant with loss of AhR target gene expression (Cyp1a1, Cyp1b1, Nqo1). Finally, we found that RelB binds to the Ahr gene at 3 sites to potentially increase its expression via transcriptional induction. These data support that RelB suppresses cigarette smoke-induced apoptosis, potentially by increasing the AhR. Together, these two proteins may comprise an important cell survival signalling pathway that reduces apoptosis upon cigarette smoke exposure.

  11. Higher cigarette prices influence cigarette purchase patterns

    PubMed Central

    Hyland, A; Bauer, J; Li, Q; Abrams, S; Higbee, C; Peppone, L; Cummings, K

    2005-01-01

    Objective: To examine cigarette purchasing patterns of current smokers and to determine the effects of cigarette price on use of cheaper sources, discount/generic cigarettes, and coupons. Background: Higher cigarette prices result in decreased cigarette consumption, but price sensitive smokers may seek lower priced or tax-free cigarette sources, especially if they are readily available. This price avoidance behaviour costs states excise tax money and dampens the health impact of higher cigarette prices. Methods: Telephone survey data from 3602 US smokers who were originally in the COMMIT (community intervention trial for smoking cessation) study were analysed to assess cigarette purchase patterns, use of discount/generic cigarettes, and use of coupons. Results: 59% reported engaging in a high price avoidance strategy, including 34% who regularly purchase from a low or untaxed venue, 28% who smoke a discount/generic cigarette brand, and 18% who report using cigarette coupons more frequently that they did five years ago. The report of engaging in a price avoidance strategy was associated with living within 40 miles of a state or Indian reservation with lower cigarette excise taxes, higher average cigarette consumption, white, non-Hispanic race/ethnicity, and female sex. Conclusion: Data from this study indicate that most smokers are price sensitive and seek out measures to purchase less expensive cigarettes, which may decrease future cessation efforts. PMID:15791017

  12. Transient and persistent metabolomic changes in plasma following chronic cigarette smoke exposure in a mouse model.

    PubMed

    Cruickshank-Quinn, Charmion I; Mahaffey, Spencer; Justice, Matthew J; Hughes, Grant; Armstrong, Michael; Bowler, Russell P; Reisdorph, Richard; Petrache, Irina; Reisdorph, Nichole

    2014-01-01

    Cigarette smoke exposure is linked to the development of a variety of chronic lung and systemic diseases in susceptible individuals. Metabolomics approaches may aid in defining disease phenotypes, may help predict responses to treatment, and could identify biomarkers of risk for developing disease. Using a mouse model of chronic cigarette smoke exposure sufficient to cause mild emphysema, we investigated whether cigarette smoke induces distinct metabolic profiles and determined their persistence following smoking cessation. Metabolites were extracted from plasma and fractionated based on chemical class using liquid-liquid and solid-phase extraction prior to performing liquid chromatography mass spectrometry-based metabolomics. Metabolites were evaluated for statistically significant differences among group means (p-value≤0.05) and fold change ≥1.5). Cigarette smoke exposure was associated with significant differences in amino acid, purine, lipid, fatty acid, and steroid metabolite levels compared to air exposed animals. Whereas 60% of the metabolite changes were reversible, 40% of metabolites remained persistently altered even following 2 months of smoking cessation, including nicotine metabolites. Validation of metabolite species and translation of these findings to human plasma metabolite signatures induced by cigarette smoking may lead to the discovery of biomarkers or pathogenic pathways of smoking-induced disease.

  13. Transient and Persistent Metabolomic Changes in Plasma following Chronic Cigarette Smoke Exposure in a Mouse Model

    PubMed Central

    Cruickshank-Quinn, Charmion I.; Mahaffey, Spencer; Justice, Matthew J.; Hughes, Grant; Armstrong, Michael; Bowler, Russell P.; Reisdorph, Richard; Petrache, Irina; Reisdorph, Nichole

    2014-01-01

    Cigarette smoke exposure is linked to the development of a variety of chronic lung and systemic diseases in susceptible individuals. Metabolomics approaches may aid in defining disease phenotypes, may help predict responses to treatment, and could identify biomarkers of risk for developing disease. Using a mouse model of chronic cigarette smoke exposure sufficient to cause mild emphysema, we investigated whether cigarette smoke induces distinct metabolic profiles and determined their persistence following smoking cessation. Metabolites were extracted from plasma and fractionated based on chemical class using liquid-liquid and solid-phase extraction prior to performing liquid chromatography mass spectrometry-based metabolomics. Metabolites were evaluated for statistically significant differences among group means (p-value≤0.05) and fold change ≥1.5). Cigarette smoke exposure was associated with significant differences in amino acid, purine, lipid, fatty acid, and steroid metabolite levels compared to air exposed animals. Whereas 60% of the metabolite changes were reversible, 40% of metabolites remained persistently altered even following 2 months of smoking cessation, including nicotine metabolites. Validation of metabolite species and translation of these findings to human plasma metabolite signatures induced by cigarette smoking may lead to the discovery of biomarkers or pathogenic pathways of smoking-induced disease. PMID:25007263

  14. Activated charcoal filter effectively reduces p-benzosemiquinone from the mainstream cigarette smoke and prevents emphysema.

    PubMed

    Dey, Neekkan; Das, Archita; Ghosh, Arunava; Chatterjee, Indu B

    2010-06-01

    In this paper, we have made a comparative evaluation of the cytotoxicity and pathophysiological effects of mainstream smoke from cellulose acetate (CA)-filtered cigarettes with that of charcoal-filtered cigarettes developed in our laboratory. Previously, we had demonstrated that the mainstream smoke from an Indian CA-filtered commercial cigarette contains p-benzosemiquinone (p-BSQ), a major, highly toxic, long-lived water-soluble radical. Here, we have examined 16 brands of different CA-filtered cigarettes including Kentucky research cigarettes, and observed that mainstream smoke from all the cigarettes contains substantial amounts of p-BSQ (100-200 μg/cigarette). We also show that when the CA filter is replaced by a charcoal filter, the amount of p-BSQ in the mainstream smoke is reduced by 73-80%, which is accompanied by a reduction of carbonyl formation in bovine serum albumin to the extent of 70- 90%. The charcoal filter also prevented cytotoxicity in A549 cells as evidenced by MTT assay, apoptosis as evidenced by FACS analysis, TUNEL assay, overexpression of Bax, activation of p53 and caspase 3, as well as emphysematous lung damage in a guinea pig model as seen by histology and morphometric analysis. The results indicate that the charcoal filter developed in our laboratory may protect smokers from cigarette smoke-induced cytotoxity, protein modification, apoptosis and emphysema.

  15. Cotinine Concentration in Serum Correlates with Tobacco Smoke-Induced Emphysema in Mice

    PubMed Central

    Xu, Xin; Su, Yunchao; Fan, Z. Hugh

    2014-01-01

    Secondhand smoke (SHS) has been associated with a variety of adverse health outcomes in nonsmokers, including emphysema (a chronic obstructive pulmonary disease). One way to detect SHS exposure is to measure the concentration of cotinine, the primary metabolite of nicotine, in bodily fluids. We have developed a method for cotinine analysis by combining micellar electrokinetic chromatography with enrichment techniques. We employed the method to measure cotinine concentrations in serum samples of mice exposed to tobacco smoke for 12 or 24 weeks and found that it was 3.1-fold or 4.8-fold higher than those exposed to room air for the same period. Further, we investigated the morphological changes in lungs of mice and observed tobacco smoke induced emphysema. Our results indicate that the method can be used to measure cotinine and there is an association between the serum cotinine concentration and tobacco smoke-induced emphysema in mice. PMID:24463700

  16. Cotinine Concentration in Serum Correlates with Tobacco Smoke-Induced Emphysema in Mice

    NASA Astrophysics Data System (ADS)

    Xu, Xin; Su, Yunchao; Fan, Z. Hugh

    2014-01-01

    Secondhand smoke (SHS) has been associated with a variety of adverse health outcomes in nonsmokers, including emphysema (a chronic obstructive pulmonary disease). One way to detect SHS exposure is to measure the concentration of cotinine, the primary metabolite of nicotine, in bodily fluids. We have developed a method for cotinine analysis by combining micellar electrokinetic chromatography with enrichment techniques. We employed the method to measure cotinine concentrations in serum samples of mice exposed to tobacco smoke for 12 or 24 weeks and found that it was 3.1-fold or 4.8-fold higher than those exposed to room air for the same period. Further, we investigated the morphological changes in lungs of mice and observed tobacco smoke induced emphysema. Our results indicate that the method can be used to measure cotinine and there is an association between the serum cotinine concentration and tobacco smoke-induced emphysema in mice.

  17. Nitrated Fatty Acids Reverse Cigarette Smoke-Induced Alveolar Macrophage Activation and Inhibit Protease Activity via Electrophilic S-Alkylation.

    PubMed

    Reddy, Aravind T; Lakshmi, Sowmya P; Muchumarri, Ramamohan R; Reddy, Raju C

    2016-01-01

    Nitrated fatty acids (NFAs), endogenous products of nonenzymatic reactions of NO-derived reactive nitrogen species with unsaturated fatty acids, exhibit substantial anti-inflammatory activities. They are both reversible electrophiles and peroxisome proliferator-activated receptor γ (PPARγ) agonists, but the physiological implications of their electrophilic activity are poorly understood. We tested their effects on inflammatory and emphysema-related biomarkers in alveolar macrophages (AMs) of smoke-exposed mice. NFA (10-nitro-oleic acid or 12-nitrolinoleic acid) treatment downregulated expression and activity of the inflammatory transcription factor NF-κB while upregulating those of PPARγ. It also downregulated production of inflammatory cytokines and chemokines and of the protease cathepsin S (Cat S), a key mediator of emphysematous septal destruction. Cat S downregulation was accompanied by decreased AM elastolytic activity, a major mechanism of septal destruction. NFAs downregulated both Cat S expression and activity in AMs of wild-type mice, but only inhibited its activity in AMs of PPARγ knockout mice, pointing to a PPARγ-independent mechanism of enzyme inhibition. We hypothesized that this mechanism was electrophilic S-alkylation of target Cat S cysteines, and found that NFAs bind directly to Cat S following treatment of intact AMs and, as suggested by in silico modeling and calculation of relevant parameters, elicit S-alkylation of Cys25 when incubated with purified Cat S. These results demonstrate that NFAs' electrophilic activity, in addition to their role as PPARγ agonists, underlies their protective effects in chronic obstructive pulmonary disease (COPD) and support their therapeutic potential in this disease.

  18. Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking.

    PubMed Central

    Lehr, H A; Weyrich, A S; Saetzler, R K; Jurek, A; Arfors, K E; Zimmerman, G A; Prescott, S M; McIntyre, T M

    1997-01-01

    Cigarette smoking within minutes induces leukocyte adhesion to the vascular wall and formation of intravascular leukocyte-platelet aggregates. We find this is inhibited by platelet-activating factor (PAF) receptor antagonists, and correlates with the accumulation of PAF-like mediators in the blood of cigarette smoke-exposed hamsters. These mediators were PAF-like lipids, formed by nonenzymatic oxidative modification of existing phospholipids, that were distinct from biosynthetic PAF. These PAF-like lipids induced isolated human monocytes and platelets to aggregate, which greatly increased their secretion of IL-8 and macrophage inflammatory protein-1alpha. Both events were blocked by a PAF receptor antagonist. Similarly, blocking the PAF receptor in vivo blocked smoke-induced leukocyte aggregation and pavementing along the vascular wall. Dietary supplementation with the antioxidant vitamin C prevented the accumulation of PAF-like lipids, and it prevented cigarette smoke-induced leukocyte adhesion to the vascular wall and formation of leukocyte-platelet aggregates. This is the first in vivo demonstration of inflammatory phospholipid oxidation products and it suggests a molecular mechanism coupling cigarette smoke with rapid inflammatory changes. Inhibition of PAF-like lipid formation and their intravascular sequela by vitamin C suggests a simple dietary means to reduce smoking-related cardiovascular disease. PMID:9153277

  19. A protocol for detecting and scavenging gas-phase free radicals in mainstream cigarette smoke.

    PubMed

    Yu, Long-Xi; Dzikovski, Boris G; Freed, Jack H

    2012-01-02

    Cigarette smoking is associated with human cancers. It has been reported that most of the lung cancer deaths are caused by cigarette smoking (5,6,7,12). Although tobacco tars and related products in the particle phase of cigarette smoke are major causes of carcinogenic and mutagenic related diseases, cigarette smoke contains significant amounts of free radicals that are also considered as an important group of carcinogens(9,10). Free radicals attack cell constituents by damaging protein structure, lipids and DNA sequences and increase the risks of developing various types of cancers. Inhaled radicals produce adducts that contribute to many of the negative health effects of tobacco smoke in the lung(3). Studies have been conducted to reduce free radicals in cigarette smoke to decrease risks of the smoking-induced damage. It has been reported that haemoglobin and heme-containing compounds could partially scavenge nitric oxide, reactive oxidants and carcinogenic volatile nitrosocompounds of cigarette smoke(4). A 'bio-filter' consisted of haemoglobin and activated carbon was used to scavenge the free radicals and to remove up to 90% of the free radicals from cigarette smoke(14). However, due to the cost-ineffectiveness, it has not been successfully commercialized. Another study showed good scavenging efficiency of shikonin, a component of Chinese herbal medicine(8). In the present study, we report a protocol for introducing common natural antioxidant extracts into the cigarette filter for scavenging gas phase free radicals in cigarette smoke and measurement of the scavenge effect on gas phase free radicals in mainstream cigarette smoke (MCS) using spin-trapping Electron Spin Resonance (ESR) Spectroscopy(1,2,14). We showed high scavenging capacity of lycopene and grape seed extract which could point to their future application in cigarette filters. An important advantage of these prospective scavengers is that they can be obtained in large quantities from byproducts of

  20. Could zinc prevent reproductive alterations caused by cigarette smoke in male rats?

    PubMed

    Garcia, Patrícia Carvalho; Piffer, Renata Carolina; Gerardin, Daniela Cristina Cecatto; Sankako, Michele Kimie; Alves de Lima, Rodrigo Otávio; Pereira, Oduvaldo Câmara Marques

    2012-01-01

    The aim of the present study was to evaluate the effects of zinc on fertility through semen parameters, testosterone level and oxidative DNA damage to spermatozoa of rats exposed to cigarette smoke. Male Wistar rats (60 days old) were divided into four groups (n = 10 per group): control, cigarette-smoking (20 cigarettes per day), zinc (zinc chloride 20 mg kg⁻¹ day⁻¹) and zinc plus cigarette-smoking (zinc chloride 20 mg kg⁻¹ day⁻¹; 20 cigarettes per day). The treatment was applied for nine weeks and the following parameters were analysed: bodyweight, wet weights of the reproductive organs and the adrenal gland, plasma testosterone concentration, testicular function (seminal analysis and daily sperm production) and sperm DNA oxidative damage. The exposure to cigarette smoke decreased testosterone concentration, the percentage of normal morphology and the motility of spermatozoa. In addition, this exposure increased sperm DNA oxidative damage. Zinc treatment protected against the toxic damage that smoking caused to spermatozoa. This study showed a correlation between smoking and possible male infertility and subfertility, and also that the majority of smoking-induced changes in spermatozoa were prevented by zinc treatment. In conclusion, zinc, an antioxidant and stimulant of cell division, can be indicated as a promising treatment in men with infertility caused by the toxic components of cigarette smoke.

  1. Brain oxidative damage restored by Sesbania grandiflora in cigarette smoke-exposed rats.

    PubMed

    Ramesh, Thiyagarajan; Sureka, Chandrabose; Bhuvana, Shanmugham; Begum, Vavamohaideen Hazeena

    2015-08-01

    Cigarette smoking has been associated with high risk of neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, etc., The present study was designed to evaluate the restorative effects of Sesbania grandiflora (S. grandiflora) on oxidative damage induced by cigarette smoke exposure in the brain of rats. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a period of 90 days and consecutively treated with S. grandiflora aqueous suspension (SGAS, 1000 mg/kg body weight per day by oral gavage) for a period of 3 weeks. The levels of protein carbonyl, nitric oxide, and activities of cytochrome P450, NADPH oxidase and xanthine oxidase were significantly increased, whereas the levels of total thiol, protein thiol, non-protein thiol, nucleic acids, tissue protein and the activities of Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were significantly diminished in the brain of rats exposed to cigarette smoke as compared with control rats. Also cigarette smoke exposure resulted in a significant alteration in brain total lipid, total cholesterol, triglycerides and phospholipids content. Treatment of SGAS is regressed these alterations induced by cigarette smoke. The results of our study suggest that S. grandiflora restores the brain from cigarette smoke induced oxidative damage. S. grandiflora could have rendered protection to the brain by stabilizing their cell membranes and prevented the protein oxidation, probably through its free radical scavenging and anti-peroxidative effect.

  2. EGF-Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis of Smoking-Induced Lesions in the Human Airway Epithelium

    PubMed Central

    Zuo, Wu-Lin; Yang, Jing; Gomi, Kazunori; Chao, IonWa; Crystal, Ronald G.; Shaykhiev, Renat

    2017-01-01

    The airway epithelium of cigarette smokers undergoes dramatic remodeling with hyperplasia of basal cells (BC) and mucus-producing cells, squamous metaplasia, altered ciliated cell differentiation and decreased junctional barrier integrity, relevant to chronic obstructive pulmonary disease and lung cancer. In this study, we show that epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG) is induced by smoking in human airway epithelium as a result of epidermal growth factor (EGF)-driven squamous differentiation of airway BC stem/progenitor cells. In turn, AREG induced a unique EGFR activation pattern in human airway BC, distinct from that evoked by EGF, leading to BC- and mucous hyperplasia, altered ciliated cell differentiation and impaired barrier integrity. Further, AREG promoted its own expression and suppressed expression of EGF, establishing an autonomous self-amplifying signaling loop in airway BC relevant for promotion of EGF-independent hyperplastic phenotypes. Thus, EGF-AREG interplay in airway BC stem/progenitor cells is one of the mechanisms that mediates the interconnected pathogenesis of all major smoking-induced lesions in the human airway epithelium. PMID:27709733

  3. Identification of gene markers in the development of smoking-induced lung cancer.

    PubMed

    Yang, Zhao; Zhuan, Bing; Yan, Ying; Jiang, Simin; Wang, Tao

    2016-01-15

    Lung cancer is a malignant tumor with high mortality in both women and men. To study the mechanisms of smoking-induced lung cancer, we analyzed microarray of GSE4115. GSE4115 was downloaded from Gene Expression Omnibus including 78 and 85 bronchial epithelium tissue samples separately from smokers with and without lung cancer. Limma package in R was used to screen differentially expressed genes (DEGs). Hierarchical cluster analysis for DEGs was conducted using orange software and visualized by distance map. Using DAVID software, functional and pathway enrichment analyses separately were conducted for the DEGs. And protein-protein interaction (PPI) network was constructed using Cytoscape software. Then, the pathscores of enriched pathways were calculated. Besides, functional features were screened and optimized using the recursive feature elimination (RFE) method. Additionally, the support vector machine (SVM) method was used to train model. Total 1923 DEGs were identified between the two groups. Hierarchical cluster analysis indicated that there were differences in gene level between the two groups. And SVM analysis indicated that the five features had potential diagnostic value. Importantly, MAPK1 (degree=30), SRC (degree=29), SMAD4 (degree=23), EEF1A1 (degree=21), TRAF2 (degree=21) and PLCG1 (degree=20) had higher degrees in the PPI network of the DEGs. They might be involved in smoking-induced lung cancer by interacting with each other (e.g. MAPK1-SMAD4, SMAD4-EEF1A1 and SRC-PLCG1). MAPK1, SRC, SMAD4, EEF1A1, TRAF2 and PLCG1 might be responsible for the development of smoking-induced lung cancer.

  4. Low-Yield Cigarettes

    MedlinePlus

    ... health consequences of smoking, cigarette manufacturers began heavily marketing cigarettes labeled "light," "low," and "mild" (or similar ... the implied promise of reduced toxicity underlying the marketing of such brands. 1,5,6 Information on ...

  5. Cigars, Cigarettes, and Adolescents

    ERIC Educational Resources Information Center

    Brooks, Ashley; Larkin, Elizabeth M. Gaier; Kishore, Sonal; Frank, Scott

    2008-01-01

    Objective: To examine public health implications of adolescent use of cigars only, cigarettes only, and both cigarettes and cigars. Methods: A cross-sectional health risk survey was administered to a random sample of 4486 high school students in a Midwestern county. Results: More adolescents reported using both cigarettes and cigars (10.6%) than…

  6. Cigarette smoke exposure reveals a novel role for the MEK/ERK1/2 MAPK pathway in regulation of CFTR

    PubMed Central

    Xu, Xiaohua; Balsiger, Robert; Tyrrell, Jean; Boyaka, Prosper N.; Tarran, Robert; Cormet-Boyaka, Estelle

    2015-01-01

    Background CFTR plays a key role in maintenance of lung fluid homeostasis. Cigarette smoke decreases CFTR expression in the lung but neither the mechanisms leading to CFTR loss, nor potential ways to prevent its loss have been identified to date. Methods The molecular mechanisms leading to down-regulation of CFTR by cigarette smoke were determined using pharmacologic inhibitors and silencing RNAs. Results Using human bronchial epithelial cells, here we show that cigarette smoke induces degradation of CFTR that is attenuated by the lysosomal inhibitors, but not proteasome inhibitors. Cigarette smoke can activate multiple signaling pathways in airway epithelial cells, including the MEK/Erk1/2 MAPK pathway regulating cell survival. Interestingly, pharmacological inhibition of the MEK/Erk1/2 MAPK pathway prevented the loss of plasma membrane CFTR upon cigarette smoke exposure. Similarly, decreased expression of Erk1/2 using silencing RNAs prevented the suppression of CFTR protein by cigarette smoke. Conversely, specific inhibitors of the JNK or p38 MAPK pathways had no effect on CFTR decrease after cigarette smoke exposure. In addition, inhibition of the MEK/Erk1/2 MAPK pathway prevented the reduction of the airway surface liquid observed upon cigarette smoke exposure of primary human airway epithelial cells. Finally, addition of the antioxidant NAC inhibited activation of Erk1/2 by cigarette smoke and precluded the cigarette smoke-induced decrease of CFTR. Conclusions These results show that the MEK/Erk1/2 MAPK pathway regulates plasma membrane CFTR in human airway cells. General Significance The MEK/Erk1/2 MAPK pathway should be considered as a target for strategies to maintain/restore CFTR expression in the lung of smokers. PMID:25697727

  7. Cyto-genotoxic effects of smoke from commercial filter and non-filter cigarettes on human bronchial and pulmonary cells.

    PubMed

    Cavallo, Delia; Ursini, Cinzia L; Fresegna, Anna M; Maiello, Raffaele; Ciervo, Aureliano; Ferrante, Riccardo; Buresti, Giuliana; Iavicoli, Sergio

    2013-01-20

    Cigarette smoke is a complex mixture of chemicals, some of which are known as carcinogens. The cyto-genotoxic effects of cigarette-smoke extract (CSE) from commercial cigarettes without (A and B) and with filter (C and D) were evaluated at different CSE concentrations on A549 and BEAS-2B cells. The particle content of the cigarette smoke and the metal composition of the CSE were also analyzed. The cells were exposed to 1-10% of the CSE from one cigarette per experiment. Cytotoxicity was evaluated by use of the MTT assay after 24h, and the lactate dehydrogenase (LDH) assay after 30min and 24h. The Fpg-modified comet assay was used to evaluate direct-oxidative DNA damage on cells exposed for 30min. As expected, unfiltered cigarette smoke (particularly from the B cigarette) contained a higher number of particles than filtered smoke. With smoke extract from the B cigarette we found a decrease in cell viability only in BEAS-2B cells. The results of the LDH test showed membrane damage for B-cigarette smoke extract, particularly in BEAS-2B cells. Extracts from unfiltered cigarette smoke induced significant direct DNA damage, to a larger extent in A549 cells. Filtered cigarette-smoke extract induced a significant direct DNA damage at 5-10%. A significant induction of oxidative DNA damage was found at the highest CSE concentration in both cell types (by smoke extracts from B and C cigarettes in A549 cells, and from A and D cigarettes in BEAS-2B cells). Smoke extracts from filter cigarettes induced less direct DNA damage than those from unfiltered cigarettes in A549 cells, probably due to a protective effect of filter. In BEAS-2B cells the smoke extract from the B-cigarette showed the highest genotoxic effect, with a concentration-dependent trend. These findings show a higher cyto-genotoxicity for smoke extracts from the B-cigarette and oxidative effects for those from the A and D cigarettes, particularly in BEAS-2B cells. Moreover, there was a higher responsiveness of A549

  8. Therapeutic Efficacy of Esomeprazole in Cotton Smoke-Induced Lung Injury Model

    PubMed Central

    Nelson, Christina; Lee, Jameisha; Ko, Kang; Sikora, Andrew G.; Bonnen, Mark D.; Enkhbaatar, Perenlei; Ghebre, Yohannes T.

    2017-01-01

    Proton pump inhibitors (PPIs) are well-known antacid drugs developed to treat gastric disorders. Emerging studies demonstrate that PPIs possess biological activities that extend beyond inhibition of H+/K+ ATPase (proton pumps) expressed in parietal cells of the stomach. Some of the extra-gastric activities of PPIs include modulation of epithelial, endothelial, and immune cell functions. Recently, we reported that PPIs suppress the expression of several proinflammatory and profibrotic molecules, as well as enhance antioxidant mechanisms in order to favorably regulate lung inflammation and fibrosis in an animal model of bleomycin-induced lung injury. In addition, several retrospective clinical studies report that the use of PPIs is associated with beneficial outcomes in chronic lung diseases including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Based on these preclinical and clinical observations, we hypothesized that PPIs ameliorate smoke-induced lung injury. Accordingly, we evaluated the pharmacological efficacy of the PPI esomeprazole in a mouse model of cotton smoke-induced lung injury. The animals were exposed to cotton smoke for 3-weeks in the presence or absence of esomeprazole treatment. We found that therapeutic administration of esomeprazole significantly inhibited the progression of fibrosis throughout the lungs of the animals in this group compared to controls. In addition, esomeprazole also reduced circulating markers of inflammation and fibrosis. Overall, our work extends the emerging anti-inflammatory and antifibrotic potential of PPIs and their role in modulation of chronic lung diseases. PMID:28184197

  9. Hypermethylation of CCND2 May Reflect a Smoking-Induced Precancerous Change in the Lung.

    PubMed

    Salskov, Alexander; Hawes, Stephen E; Stern, Joshua E; Feng, Qinghua; Jordan, C Diana; Wiens, Linda; Rasey, Janet; Lu, Hiep; Kiviat, Nancy B; Vesselle, Hubert

    2011-01-01

    It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers) for hypermethylation of 19 genes previously observed to be hypermethylated in nonsmall cell lung cancers. Only APC (39%), CCND2 (21%), CDH1 (7%), and RARB (4%) were hypermethylated in >2% of these cancer-free subjects. CCND2 was hypermethylated more frequently in ever-smokers (26%) than in never-smokers (3%). CCND2 hypermethylation was also associated with increased age and upper lobe sample location. APC was frequently hypermethylated in both ever-smokers (41%) and never-smokers (30%). BVES, CDH13, CDKN2A (p16), CDKN2B, DAPK1, IGFBP3, IGSF4, KCNH5, KCNH8, MGMT, OPCML, PCSK6, RASSF1, RUNX, and TMS1 were rarely hypermethylated (<2%) in all subjects. Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung.

  10. A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: a randomized-controlled trial.

    PubMed

    Del Bo', Cristian; Porrini, Marisa; Fracassetti, Daniela; Campolo, Jonica; Klimis-Zacas, Dorothy; Riso, Patrizia

    2014-12-01

    Cigarette smoking causes oxidative stress, hypertension and endothelial dysfunction. Polyphenol-rich foods may prevent these conditions. We investigated the effect of a single serving of fresh-frozen blueberry intake on peripheral arterial function and arterial stiffness in young smokers. Sixteen male smokers were recruited for a 3-armed randomized-controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300 g of blueberry) + smoking; control treatment (300 mL of water with sugar) + smoking. Each treatment was separated by one week of wash-out period. The blood pressure, heart rate, peripheral arterial function (reactive hyperemia and Framingham reactive hyperemia), and arterial stiffness (digital augmentation index, digital augmentation index normalized for a heart rate of 75 bpm) were measured before and 20 min after smoking with Endo-PAT2000. Smoking impaired the blood pressure, heart rate and peripheral arterial function, but did not affect the arterial stiffness. Blueberry consumption counteracted the impairment of the reactive hyperemia index induced by smoking (-4.4 ± 0.8% blueberry treatment vs. -22.0 ± 1.1% smoking treatment, p < 0.01) and Framingham reactive hyperemia (+28.3 ± 19.2% blueberry treatment vs. -42.8 ± 20.0% smoking treatment, p < 0.0001), and the increase of systolic blood pressure (+8.4 ± 0.02% blueberry treatment vs. +13.1 ± 0.02% smoking treatment, mmHg, p < 0.05) after cigarette smoking. No effect was observed for arterial stiffness and other vital signs. In conclusion, data obtained suggest a protective role of blueberry on reactive hyperemia, Framingham reactive hyperemia, and systolic blood pressure in subjects exposed to smoke of one cigarette. Future studies are necessary to elucidate the mechanisms involved.

  11. Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo.

    PubMed

    Shaykhiev, Renat; Otaki, Fouad; Bonsu, Prince; Dang, David T; Teater, Matthew; Strulovici-Barel, Yael; Salit, Jacqueline; Harvey, Ben-Gary; Crystal, Ronald G

    2011-03-01

    The apical junctional complex (AJC), composed of tight and adherens junctions, maintains epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating airway epithelial AJC integrity. Transcriptome analysis revealed global down-regulation of physiological AJC gene expression in the airway epithelium of healthy smokers (n = 59) compared to nonsmokers (n = 53) in association with changes in canonical epithelial differentiation pathways such as PTEN signaling accompanied by induction of cancer-related AJC components. The overall expression of AJC-related genes was further decreased in COPD smokers (n = 23). Exposure of airway epithelial cells to cigarette smoke extract in vitro resulted in down-regulation of several AJC genes paralleled by decreased transepithelial resistance. Thus, cigarette smoking induces transcriptional reprogramming of airway epithelial AJC architecture from its physiological pattern necessary for barrier function toward a disease-associated molecular phenotype.

  12. 1α,25-dihydroxyvitamin D₃ counteracts the effects of cigarette smoke in airway epithelial cells.

    PubMed

    Zhang, Ruhui; Zhao, Haijin; Dong, Hangming; Zou, Fei; Cai, Shaoxi

    2015-06-01

    Cigarette smoke extracts (CSE) alter calpain-1 expression via ERK signaling pathway in bronchial epithelial cells. 1α,25-dihydroxyvitamin D3 (1,25D3) inhibits cigarette smoke-induced epithelial barrier disruption. This study was aimed to explore whether the 1,25D3 counteracted the CSE effects in a human bronchial epithelial cell line (16HBE). In particular, transepithelial electrical resistance (TER) and permeability, expression and distribution of E-cadherin and β-catenin, calpain-1 expression, and ERK phosphorylation were assessed in the CSE-stimulated 16HBE cells. The CSE induced the ERK phosphorylation, improved the calpain-1 expression, increased the distribution anomalies and the cleaving of E-cadherin and β-catenin, and resulted in the TER reduction and the permeability increase. The 1,25D3 reduced these pathological changes. The 1,25D3 mediated effects were associated with a reduced ERK phosphorylation. In conclusion, the present study provides compelling evidences that the 1,25D3 may be considered a possible valid therapeutic option in controlling the cigarette smoke-induced epithelial barrier disruption.

  13. Resolvins attenuate inflammation and promote resolution in cigarette smoke-exposed human macrophages.

    PubMed

    Croasdell, Amanda; Thatcher, Thomas H; Kottmann, R Matthew; Colas, Romain A; Dalli, Jesmond; Serhan, Charles N; Sime, Patricia J; Phipps, Richard P

    2015-10-15

    Inflammation is a protective response to injury, but it can become chronic, leading to tissue damage and disease. Cigarette smoke causes multiple inflammatory diseases, which account for thousands of deaths and cost billions of dollars annually. Cigarette smoke disrupts the function of immune cells, such as macrophages, by prolonging inflammatory signaling, promoting oxidative stress, and impairing phagocytosis, contributing to increased incidence of infections. Recently, new families of lipid-derived mediators, "specialized proresolving mediators" (SPMs), were identified. SPMs play a critical role in the active resolution of inflammation by counterregulating proinflammatory signaling and promoting resolution pathways. We have identified dysregulated concentrations of lipid mediators in exhaled breath condensate, bronchoalveolar lavage fluid, and serum from patients with chronic obstructive pulmonary disease (COPD). In human alveolar macrophages from COPD and non-COPD patients, D-series resolvins decreased inflammatory cytokines and enhanced phagocytosis. To further investigate the actions of resolvins on human cells, macrophages were differentiated from human blood monocytes and treated with D-series resolvins and then exposed to cigarette smoke extract. Resolvins significantly suppressed macrophage production of proinflammatory cytokines, enzymes, and lipid mediators. Resolvins also increased anti-inflammatory cytokines, promoted an M2 macrophage phenotype, and restored cigarette smoke-induced defects in phagocytosis, highlighting the proresolving functions of these molecules. These actions were receptor-dependent and involved modulation of canonical and noncanonical NF-κB expression, with the first evidence for SPM action on alternative NF-κB signaling. These data show that resolvins act on human macrophages to attenuate cigarette smoke-induced inflammatory effects through proresolving mechanisms and provide new evidence of the therapeutic potential of SPMs.

  14. Vapours of US and EU Market Leader Electronic Cigarette Brands and Liquids Are Cytotoxic for Human Vascular Endothelial Cells.

    PubMed

    Putzhammer, Raphaela; Doppler, Christian; Jakschitz, Thomas; Heinz, Katharina; Förste, Juliane; Danzl, Katarina; Messner, Barbara; Bernhard, David

    2016-01-01

    The present study was conducted to provide toxicological data on e-cigarette vapours of different e-cigarette brands and liquids from systems viewed as leaders in the e-cigarette market and to compare e-cigarette vapour toxicity to the toxicity of conventional strong high-nicotine cigarette smoke. Using an adapted version of a previously constructed cigarette smoke constituent sampling device, we collected the hydrophilic fraction of e-cigarette vapour and exposed human umbilical vein endothelial cells (HUVECs) to the mixture of compounds present in the vapour of 4 different single-use e-cigarettes, 6 different liquid vapours produced by the same refillable e-cigarette, and one e-cigarette with an exchangeable liquid cartridge. After incubation of cells with various concentrations and for various periods of time we analysed cell death induction, proliferation rates, the occurrence of intra-cellular reactive oxygen species, cell morphology, and we also measured e-cigarette heating coil temperatures. Overall, conventional cigarette smoke extract showed the most severe impact on endothelial cells. However, some e-cigarette vapour extracts showed high cytotoxicity, inhibition of cell proliferation, and alterations in cell morphology, which were comparable to conventional high-nicotine cigarettes. The vapours generated from different liquids using the same e-cigarette show substantial differences, pointing to the liquids as an important source for toxicity. E-cigarette vapour-mediated induction of oxidative stress was significant in one out of the 11 analysed vapours. There is a high variability in the acute cytotoxicity of e-cigarette vapours depending on the liquid and on the e-cigarettes used. Some products showed toxic effects close to a conventional high-nicotine cigarette. Liquid nicotine, menthol content, and the formation of acute intracellular reactive oxygen species do not seem to be the central elements in e-cigarette vapour toxicity.

  15. Vapours of US and EU Market Leader Electronic Cigarette Brands and Liquids Are Cytotoxic for Human Vascular Endothelial Cells

    PubMed Central

    Putzhammer, Raphaela; Doppler, Christian; Jakschitz, Thomas; Heinz, Katharina; Förste, Juliane; Danzl, Katarina; Messner, Barbara; Bernhard, David

    2016-01-01

    The present study was conducted to provide toxicological data on e-cigarette vapours of different e-cigarette brands and liquids from systems viewed as leaders in the e-cigarette market and to compare e-cigarette vapour toxicity to the toxicity of conventional strong high-nicotine cigarette smoke. Using an adapted version of a previously constructed cigarette smoke constituent sampling device, we collected the hydrophilic fraction of e-cigarette vapour and exposed human umbilical vein endothelial cells (HUVECs) to the mixture of compounds present in the vapour of 4 different single-use e-cigarettes, 6 different liquid vapours produced by the same refillable e-cigarette, and one e-cigarette with an exchangeable liquid cartridge. After incubation of cells with various concentrations and for various periods of time we analysed cell death induction, proliferation rates, the occurrence of intra-cellular reactive oxygen species, cell morphology, and we also measured e-cigarette heating coil temperatures. Overall, conventional cigarette smoke extract showed the most severe impact on endothelial cells. However, some e-cigarette vapour extracts showed high cytotoxicity, inhibition of cell proliferation, and alterations in cell morphology, which were comparable to conventional high-nicotine cigarettes. The vapours generated from different liquids using the same e-cigarette show substantial differences, pointing to the liquids as an important source for toxicity. E-cigarette vapour-mediated induction of oxidative stress was significant in one out of the 11 analysed vapours. There is a high variability in the acute cytotoxicity of e-cigarette vapours depending on the liquid and on the e-cigarettes used. Some products showed toxic effects close to a conventional high-nicotine cigarette. Liquid nicotine, menthol content, and the formation of acute intracellular reactive oxygen species do not seem to be the central elements in e-cigarette vapour toxicity. PMID:27351725

  16. Evaluating the forced oscillation technique in the detection of early smoking-induced respiratory changes

    PubMed Central

    Faria, Alvaro CD; Lopes, Agnaldo J; Jansen, José M; Melo, Pedro L

    2009-01-01

    Background Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD). The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system. The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD in its initial phases. Thus, the purpose of this study was twofold: (1) to evaluate the ability of FOT to detect early smoking-induced respiratory alterations; and (2) to compare the sensitivity of FOT with spirometry in a sample of low tobacco-dose subjects. Methods Results from a group of 28 smokers with a tobacco consumption of 11.2 ± 7.3 pack-years were compared with a control group formed by 28 healthy subjects using receiver operating characteristic (ROC) curves and a questionnaire as a gold standard. The early adverse effects of smoking were adequately detected by the absolute value of the respiratory impedance (Z4Hz), the intercept resistance (R0), and the respiratory system dynamic compliance (Crs, dyn). Z4Hz was the most accurate parameter (Se = 75%, Sp = 75%), followed by R0 and Crs, dyn. The performances of the FOT parameters in the detection of the early effects of smoking were higher than that of spirometry (p < 0.05). Conclusion This study shows that FOT can be used to detect early smoking-induced respiratory changes while these pathologic changes are still potentially reversible. These findings support the use of FOT as a versatile clinical diagnostic tool in aiding COPD prevention and treatment. PMID:19781078

  17. Cigarette Smoke Extract-Induced Oxidative Stress and Fibrosis-Related Genes Expression in Orbital Fibroblasts from Patients with Graves' Ophthalmopathy.

    PubMed

    Kau, Hui-Chuan; Wu, Shi-Bei; Tsai, Chieh-Chih; Liu, Catherine Jui-Ling; Wei, Yau-Huei

    2016-01-01

    Cigarette smoking is the most important risk factor for the development or deterioration of Graves' ophthalmopathy. Smoke-induced increased generation of reactive oxygen species may be involved. However, it remains to be clarified how orbital fibroblasts are affected by cigarette smoking. Our study demonstrated that Graves' orbital fibroblasts have exaggerated response to cigarette smoke extract challenge along with increased oxidative stress, fibrosis-related genes expression, especially connective tissue growth factor, and intracellular levels of transforming growth factor-β1 and interleukin-1β. The findings obtained in this study provide some clues for the impact of cigarette smoking on Graves' ophthalmopathy and offer a theoretical basis for the potential and rational use of antioxidants in treating Graves' ophthalmopathy.

  18. The effects of phenethyl isothiocyanate, N-acetylcysteine and green tea on tobacco smoke-induced lung tumors in strain A/J mice.

    PubMed

    Witschi, H; Espiritu, I; Yu, M; Willits, N H

    1998-10-01

    Male and female strain A/J mice were exposed to a mixture of cigarette sidestream and mainstream smoke at a chamber concentration of total suspended particulates of 82.5 mg/m3. Exposure time was 6 h/day, 5 days/week for 5 months. The animals were allowed to recover for another 4 months in filtered air before sacrifice and lung tumor count. Male animals were fed either 0.2% N-acetylcysteine (NAC) or 0.05% phenethyl isothiocyanate (PEITC) in diet AIN-76A with 5% corn oil added. Female animals received normal laboratory chow and were given a 1.25% extract of green tea in the drinking water. Corresponding control groups were fed diets without NAC or PEITC or given plain tap water. Exposure to tobacco smoke increased lung tumor multiplicity to 1.1-1.6 tumors/lung, significantly higher than control values (0.5-1.0 tumors/lung). None of the putative chemopreventive agents (NAC, PEITC or green tea extract) had a protective effect. In positive control experiments, PEITC significantly reduced both lung tumor multiplicity and incidence in mice treated with the tobacco smoke-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In mice treated with three different doses of urethan and fed NAC in the diet, a significant reduction in lung tumor multiplicity was found only at one dose level. Green tea extract did not reduce lung tumor multiplicity in animals treated with a single dose of NNK. It was concluded that successful chemoprevention of tobacco smoke-induced lung tumorigenesis might require administration of several chemopreventive agents rather than just a single one.

  19. Cytogenetic effects of cigarette smoke on pulmonary alveolar macrophages of the rat

    SciTech Connect

    Rithidech, K.; Chen, B.T.; Mauderly, J.L.; Whorton, E.B. Jr.; Brooks, A.L. )

    1989-01-01

    To determine accurately the potential genetic damage induced by toxic inhaled agents, the cells that receive a high concentration of such agents should be analyzed. Pulmonary alveolar macrophages (PAMs) represent such cells. The authors compared the cytogenetic effects of cigarette smoke on PAMs of rats exposed repeatedly by different methods. This study was part of a larger investigation of the health effects resulting from different methods of exposing rats to cigarette smoke. Fischer 344/N male rats were randomly selected from five different exposure groups. The rats were exposed 6 hr/day, 5 days/week for 22-24 days. All smoke-exposed rats received the same daily concentrations {times} time product of cigarette smoke. Rats were injected intraperitoneally with colchicine at the end of exposure. PAMs were obtained by lung lavage and chromosomal damage was measured. Highly significant smoke-induced differences in both structural and numerical aberrations were observed in continuously exposed rats vs. sham controls, regardless route of exposure. The structural aberrations observed were chromatid-type deletions. Both hypoploid and hyperploid cells were detected. The data suggest that cigarette smoke is clastogenic and may disrupt spindle-fiber formation. These activities may play a role in the induction of human carcinogenesis caused by cigarette smoke exposure.

  20. Characterization of the third component of complement (C3) after activation by cigarette smoke

    SciTech Connect

    Kew, R.R.; Ghebrehiwet, B.; Janoff, A.

    1987-08-01

    Activation of lung complement by tobacco smoke may be an important pathogenetic factor in the development of pulmonary emphysema in smokers. We previously showed that cigarette smoke can modify C3 and activate the alternative pathway of complement in vitro. However, the mechanism of C3 activation was not fully delineated in these earlier studies. In the present report, we show that smoke-treated C3 induces cleavage of the alternative pathway protein, Factor B, when added to serum containing Mg-EGTA. This effect of cigarette smoke is specific for C3 since smoke-treated C4, when added to Mg-EGTA-treated serum, fails to activate the alternative pathway and fails to induce Factor B cleavage. Smoke-modified C3 no longer binds significant amounts of (/sup 14/C)methylamine (as does native C3), and relatively little (/sup 14/C)methylamine is incorporated into its alpha-chain. Thus, prior internal thiolester bond cleavage appears to have occurred in C3 activated by cigarette smoke. Cigarette smoke components also induce formation of noncovalently associated, soluble C3 multimers, with a Mr ranging from 1 to 10 million. However, prior cleavage of the thiolester bond in C3 with methylamine prevents the subsequent formation of these smoke-induced aggregates. These data indicate that cigarette smoke activates the alternative pathway of complement by specifically modifying C3 and that these modifications include cleavage of the thiolester bond in C3 and formation of noncovalently linked C3 multimers.

  1. E-Cigarettes

    MedlinePlus

    ... that are known to be harmful. Scientists are studying the health effects of using e-cigarettes. New information is coming in, but they don't have the answers yet. Although FDA is working to regulate e-cigarettes, currently they are not ...

  2. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    SciTech Connect

    Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan; Wen Fuqiang

    2010-05-15

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  3. Ending the cigarette pandemic.

    PubMed

    Richmond, J B

    1983-12-01

    1 year after the issuance of the original Surgeon General's report, Congress passed the Federal Cigarette Labeling Advertising Act, requiring all cigarette packages distributed in the US to carry a Surgeon General's warning that smoking may be hazardous to health. Congress pased the Public Health Cigarette Smoking Act in 1969. This banned cigarette advertising from radio and television. The Surgeon General published the most comprehensive volume on smoking ever issued in the US in 1979, the 15th anniversary of the 1st report. The data on cigarette smoking's adverse effects on health were overwhelming, and the press recognized this. No longer able to rely on journalists to cast doubt on the reliability of the data, the industry changed its strategy by attempting to portray smoking as a civil rights issue. The tobacco industry began to pour millions of dollars into campaigns to prevent the passage of municipal, state, and federal legislation that would ban cigarette advertising or restrict smoking in public places and at the work site. "Healthy People," the Surgeon General's 1st report on health promotion and disease prevention, emphasized the necessary future direction of medicine: prevention. Efforts to end the cigarette pandemic will need to focus on the following in the future: an end to the victimization of women; a greater focus on adolescents; more effective strategies for smoking cessation; more attention to clean indoor air rights; abandonment of recommendations to switch to low-tar, low-nicotine cigarettes; and revelation of chemical additives in cigarettes. The epidemiologists have now documented the devastating nature of the health problems attributable to cigarette smoking, but the minimal budgetary allocations to fight smoking testify to the lack of political will on the part of government.

  4. Cigarette smoke inhibition of ion transport in canine tracheal epithelium

    SciTech Connect

    Welsh, M.J.

    1983-06-01

    To determine the effect of cigarette smoke on airway epithelial ion transport, the electrical properties and transepithelial Na and Cl fluxes were measured in canine tracheal epithelium. In vivo, the inhalation of the smoke from one cigarette acutely and reversibly decreased the electrical potential difference across the tracheal epithelium. In vitro, exposure of the mucosal surface of the epithelium to cigarette smoke decreased the short circuit current and transepithelial resistance. The decrease in short circuit current was due to an inhibition of the rate of Cl secretion with minimal effect on the rate of Na absorption. The effect of cigarette smoke was reversible, was not observed upon exposure of the submucosal surface to smoke, and was most pronounced when secretion was stimulated. The particulate phase of smoke was largely responsible for the inhibitory effect, since filtering the smoke minimized the effect. The effect of cigarette smoke was not prevented by addition of antioxidants to the bathing solutions, suggesting that the inhibition of Cl secretion cannot be entirely attributed to an oxidant mechanism. These results indicate that cigarette smoke acutely inhibits active ion transport by tracheal epithelium, both in vivo and in vitro. This effect may explain, in part, both the abnormal mucociliary clearance and the airway disease observed in cigarette smokers.

  5. Noni juice improves serum lipid profiles and other risk markers in cigarette smokers.

    PubMed

    Wang, Mian-Ying; Peng, Lin; Weidenbacher-Hoper, Vicki; Deng, Shixin; Anderson, Gary; West, Brett J

    2012-01-01

    Cigarette smoke-induced oxidative stress leads to dyslipidemia and systemic inflammation. Morinda citrifolia (noni) fruit juice has been found previously to have a significant antioxidant activity. One hundred thirty-two adult heavy smokers completed a randomized, double blind, placebo-controlled clinical trial designed to investigate the effect of noni juice on serum cholesterol, triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), high-sensitivity C-reactive protein (hs-CRP), and homocysteine. Volunteers drank noni juice or a fruit juice placebo daily for one month. Drinking 29.5 mL to 188 mL of noni juice per day significantly reduced cholesterol levels, triglycerides, and hs-CRP. Decreases in LDL and homocysteine, as well increases in HDL, were also observed among noni juice drinkers. The placebo, which was devoid of iridoid glycosides, did not significantly influence blood lipid profiles or hs-CRP. Noni juice was able to mitigate cigarette smoke-induced dyslipidemia, an activity associated with the presence of iridoids.

  6. Chronic cigarette smoking alters erythrocyte membrane lipid composition and properties in male human volunteers.

    PubMed

    Padmavathi, Pannuru; Reddy, Vaddi Damodara; Kavitha, Godugu; Paramahamsa, Maturu; Varadacharyulu, Nallanchakravarthula

    2010-11-01

    Cigarette smoking is a major lifestyle factor influencing the health of human beings. The present study investigates smoking induced alterations on the erythrocyte membrane lipid composition, fluidity and the role of nitric oxide. Thirty experimental and control subjects (age 35+/-8) were selected for the study. Experimental subjects smoke 12+/-2 cigarettes per day for 7-10 years. In smokers elevated nitrite/nitrate levels in plasma and red cell lysates were observed. Smokers showed increased hemolysis, erythrocyte membrane lipid peroxidation, protein carbonyls, C/P ratio (cholesterol and phospholipid ratio), anisotropic (gamma) value with decreased Na(+)/K(+)-ATPase activity and sulfhydryl groups. Alterations in smokers erythrocyte membrane individual phospholipids were also evident from the study. Red cell lysate nitric oxide positively correlated with C/P ratio (r=0.565) and fluorescent anisotropic (gamma) value (r=0.386) in smokers. Smoking induced generation of reactive oxygen/nitrogen species might have altered erythrocyte membrane physico-chemical properties.

  7. Through the smoke: Use of in vivo and in vitro cigarette smoking models to elucidate its effect on female fertility

    SciTech Connect

    Camlin, Nicole J.; McLaughlin, Eileen A.; Holt, Janet E.

    2014-12-15

    A finite number of oocytes are established within the mammalian ovary prior to birth to form a precious ovarian reserve. Damage to this limited pool of gametes by environmental factors such as cigarette smoke and its constituents therefore represents a significant risk to a woman's reproductive capacity. Although evidence from human studies to date implicates a detrimental effect of cigarette smoking on female fertility, these retrospective studies are limited and present conflicting results. In an effort to more clearly understand the effect of cigarette smoke, and its chemical constituents, on female fertility, a variety of in vivo and in vitro animal models have been developed. This article represents a systematic review of the literature regarding four of experimental model types: 1) direct exposure of ovarian cells and follicles to smoking constituents’ in vitro, 2) direct exposure of whole ovarian tissue with smoking constituents in vitro, 3) whole body exposure of animals to smoking constituents and 4) whole body exposure of animals to cigarette smoke. We summarise key findings and highlight the strengths and weaknesses of each model system, and link these to the molecular mechanisms identified in smoke-induced fertility changes. - Highlights: • In vivo exposure to individual cigarette smoke chemicals alters female fertility. • The use of in vitro models in determining molecular mechanisms • Whole cigarette smoke inhalation animal models negatively affect ovarian function.

  8. Analysis of the Effects of Cigarette Smoke on Staphylococcal Virulence Phenotypes

    PubMed Central

    McEachern, Elisa K.; Hwang, John H.; Sladewski, Katherine M.; Nicatia, Shari; Dewitz, Carola; Mathew, Denzil P.; Nizet, Victor

    2015-01-01

    Cigarette smoking is the leading preventable cause of death, disease, and disability worldwide. It is well established that cigarette smoke provokes inflammatory activation and impairs antimicrobial functions of human immune cells. Here we explore whether cigarette smoke likewise affects the virulence properties of an important human pathogen, Staphylococcus aureus, and in particular methicillin-resistant S. aureus (MRSA), one of the leading causes of invasive bacterial infections. MRSA colonizes the nasopharynx and is thus exposed to inhalants, including cigarette smoke. MRSA exposed to cigarette smoke extract (CSE-MRSA) was more resistant to macrophage killing (4-fold higher survival; P < 0.0001). CSE-MRSA demonstrated reduced susceptibility to cell lysis (1.78-fold; P = 0.032) and antimicrobial peptide (AMP) (LL-37) killing (MIC, 8 μM versus 4 μM). CSE modified the surface charge of MRSA in a dose-dependent fashion, impairing the binding of particles with charge similar to that of AMPs by 90% (P < 0.0001). These changes persisted for 24 h postexposure, suggesting heritable modifications. CSE exposure increased hydrophobicity by 55% (P < 0.0001), which complemented findings of increased MRSA adherence and invasion of epithelial cells. CSE induced upregulation of mprF, consistent with increased MRSA AMP resistance. S. aureus without mprF had no change in surface charge upon exposure to CSE. In vivo, CSE-MRSA pneumonia induced higher mouse mortality (40% versus 10%) and increased bacterial burden at 8 and 20 h postinfection compared to control MRSA-infected mice (P < 0.01). We conclude that cigarette smoke-induced immune resistance phenotypes in MRSA may be an additional factor contributing to susceptibility to infectious disease in cigarette smokers. PMID:25824841

  9. Analysis of the effects of cigarette smoke on staphylococcal virulence phenotypes.

    PubMed

    McEachern, Elisa K; Hwang, John H; Sladewski, Katherine M; Nicatia, Shari; Dewitz, Carola; Mathew, Denzil P; Nizet, Victor; Crotty Alexander, Laura E

    2015-06-01

    Cigarette smoking is the leading preventable cause of death, disease, and disability worldwide. It is well established that cigarette smoke provokes inflammatory activation and impairs antimicrobial functions of human immune cells. Here we explore whether cigarette smoke likewise affects the virulence properties of an important human pathogen, Staphylococcus aureus, and in particular methicillin-resistant S. aureus (MRSA), one of the leading causes of invasive bacterial infections. MRSA colonizes the nasopharynx and is thus exposed to inhalants, including cigarette smoke. MRSA exposed to cigarette smoke extract (CSE-MRSA) was more resistant to macrophage killing (4-fold higher survival; P < 0.0001). CSE-MRSA demonstrated reduced susceptibility to cell lysis (1.78-fold; P = 0.032) and antimicrobial peptide (AMP) (LL-37) killing (MIC, 8 μM versus 4 μM). CSE modified the surface charge of MRSA in a dose-dependent fashion, impairing the binding of particles with charge similar to that of AMPs by 90% (P < 0.0001). These changes persisted for 24 h postexposure, suggesting heritable modifications. CSE exposure increased hydrophobicity by 55% (P < 0.0001), which complemented findings of increased MRSA adherence and invasion of epithelial cells. CSE induced upregulation of mprF, consistent with increased MRSA AMP resistance. S. aureus without mprF had no change in surface charge upon exposure to CSE. In vivo, CSE-MRSA pneumonia induced higher mouse mortality (40% versus 10%) and increased bacterial burden at 8 and 20 h postinfection compared to control MRSA-infected mice (P < 0.01). We conclude that cigarette smoke-induced immune resistance phenotypes in MRSA may be an additional factor contributing to susceptibility to infectious disease in cigarette smokers.

  10. Effect of Cigarette Smoking on Concentrations of Cadmium and Lead and on the Oxidative Damage in Human Spermatozoa

    NASA Astrophysics Data System (ADS)

    Kiziler, Ali Riza; Aydemir, Birsen; Onaran, Ilhan; Alici, Bülent; Özkara, Hamdi; Akyolcu, Mehmet Can

    2007-04-01

    Cigarette smoking induced a significant oxidant effect to free radical-related male infertility. Semen and blood obtained from 50 subfertile men (n=26 smokers, n=24 nonsmokers) and from 45 fertile men (n=23 smokers, n=22 nonsmokers) volunteers were examined. The levels of ROS, MDA and protein carbonyls were significantly increased in smokers subfertile men. The results indicate that Cd and Pb levels of smoking subfertile men in seminal plasma and spermatozoa could affect semen quality and oxidative damage in human sperm cells.

  11. Effects of exposure to cigarette smoke on intestinal propulsion in rats.

    PubMed

    Furuno, K; Okazaki, M; Eto, K; Kawasaki, H; Gomita, Y

    1995-08-01

    The effects of acute exposure to cigarette smoke and systemic administration of nicotine on intestinal propulsion were investigated in rats. The propulsive activity was measured as migration of charcoal powder in the intestine. This activity was suppressed by acute exposure (10 min) to cigarette smoke and by nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was more marked in the rats given nicotine than in those exposed to cigarette smoke, whereas the plasma concentrations of nicotine in both rats were similar. These results suggest that acute exposure to cigarette smoke and nicotine administration delay gastric emptying and/or suppress intestinal propulsion, and that some components other than nicotine contained in cigarette smoke may attenuate the suppression of intestinal propulsion induced by nicotine.

  12. The Effect of Different Doses of Cigarette Smoke in a Mouse Lung Tumor Model

    PubMed Central

    Santiago, Ludmilla Nadir; de Camargo Fenley, Juliana; Braga, Lúcia Campanario; Cordeiro, José Antônio; Cury, Patrícia M.

    2009-01-01

    Few studies have used Balb/c mice as an animal model for lung carcinogenesis. In this study, we investigated the effect of different doses of cigarette smoking in the urethane-induced Balb/c mouse lung cancer model. After injection of 3mg/kg urethane intraperitoneally, the mice were then exposed to tobacco smoke once or twice a day, five times a week, in a closed chamber. The animals were randomly divided into four groups. The control group (G0) received urethane only. The experimental groups (G1, G2 and G3) received urethane and exposure to the smoke of 3 cigarettes for 10 minutes once a day, 3 cigarettes for 10 minutes twice a day, and 6 cigarettes for 10 minutes twice a day, respectively. The mice were sacrificed after 16 weeks of exposure, and the number of nodules and hyperplasia in the lungs was counted. The results showed no statistically significant difference in the mean number of nodules and hyperplasia among the different groups, suggesting that the Balb/c mice are not suitable to study the pathogenesis of tobacco smoking-induced tumor progression in the lungs. PMID:19079653

  13. Glutathione Peroxidase-1 Suppresses the Unfolded Protein Response upon Cigarette Smoke Exposure

    PubMed Central

    Baumlin, Nathalie; Salathe, Matthias A.; D'Armiento, Jeanine M.

    2016-01-01

    Oxidative stress provokes endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) in the lungs of chronic obstructive pulmonary (COPD) subjects. The antioxidant, glutathione peroxidase-1 (GPx-1), counters oxidative stress induced by cigarette smoke exposure. Here, we investigate whether GPx-1 expression deters the UPR following exposure to cigarette smoke. Expression of ER stress markers was investigated in fully differentiated normal human bronchial epithelial (NHBE) cells isolated from nonsmoking, smoking, and COPD donors and redifferentiated at the air liquid interface. NHBE cells from COPD donors expressed heightened ATF4, XBP1, GRP78, GRP94, EDEM1, and CHOP compared to cells from nonsmoking donors. These changes coincided with reduced GPx-1 expression. Reintroduction of GPx-1 into NHBE cells isolated from COPD donors reduced the UPR. To determine whether the loss of GPx-1 expression has a direct impact on these ER stress markers during smoke exposure, Gpx-1−/− mice were exposed to cigarette smoke for 1 year. Loss of Gpx-1 expression enhanced cigarette smoke-induced ER stress and apoptosis. Equally, induction of ER stress with tunicamycin enhanced antioxidant expression in mouse precision-cut lung slices. Smoke inhalation also exacerbated the UPR response during respiratory syncytial virus infection. Therefore, ER stress may be an antioxidant-related pathophysiological event in COPD. PMID:28070146

  14. Effects of using electronic cigarettes on nicotine delivery and cardiovascular function in comparison with regular cigarettes.

    PubMed

    Yan, X Sherwin; D'Ruiz, Carl

    2015-02-01

    The development of electronic cigarettes (e-cigs) has the potential to offer a less harmful alternative for tobacco users. This clinical study was designed to characterize e-cig users' exposure to nicotine, and to investigate the acute effects of e-cigs on the hemodynamic measurements (blood pressure and heart rate) in comparison with the effects of regular smoking. Five e-cigs and one Marlboro® cigarette were randomized for twenty-three participants under two exposure scenarios from Day 1 to Day 11: half-hour controlled administration and one hour ad lib use. The nicotine plasma concentrations after 1.5h of product use (C90) were significantly lower in the users of e-cigs than of Marlboro® cigarettes. The combination of glycerin and propylene glycol as the vehicle facilitated delivery of more nicotine than glycerin alone. The heart rate, systolic and diastolic blood pressure were significantly elevated after use of Marlboro® cigarettes, but the elevation was less after use of most of the e-cigs. Use of e-cigs had no impact on the exhaled CO levels, whereas the Marlboro® cigarette significantly increased the exhaled CO more than 8 times above the baseline. In conclusion, e-cigs could be a less harmful alternative for tobacco users.

  15. Metabolic Effects of Nicotine Gum and Cigarette Smoking: Potential Implications for Postcessation Weight Gain?

    ERIC Educational Resources Information Center

    Klesges, Robert C.; And Others

    1991-01-01

    Twenty smoking women participated in nicotine gum and smoking administration, after which resting energy expenditures (REEs) were measured. Results indicated acute increase in REE for both nicotine gum and cigarettes. Metabolic rates for nicotine gum slowly returned to baseline; rates for cigarettes quickly fell significantly below baseline.…

  16. Metabolomic profiles of current cigarette smokers.

    PubMed

    Hsu, Ping-Ching; Lan, Renny S; Brasky, Theodore M; Marian, Catalin; Cheema, Amrita K; Ressom, Habtom W; Loffredo, Christopher A; Pickworth, Wallace B; Shields, Peter G

    2017-02-01

    Smoking-related biomarkers for lung cancer and other diseases are needed to enhance early detection strategies and to provide a science base for tobacco product regulation. An untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF MS) totaling 957 assays was used in a novel experimental design where 105 current smokers smoked two cigarettes 1 h apart. Blood was collected immediately before and after each cigarette allowing for within-subject replication. Dynamic changes of the metabolomic profiles from smokers' four blood samples were observed and biomarkers affected by cigarette smoking were identified. Thirty-one metabolites were definitively shown to be affected by acute effect of cigarette smoking, uniquely including menthol-glucuronide, the reduction of glutamate, oleamide, and 13 glycerophospholipids. This first time identification of a menthol metabolite in smokers' blood serves as proof-of-principle for using metabolomics to identify new tobacco-exposure biomarkers, and also provides new opportunities in studying menthol-containing tobacco products in humans. Gender and race differences also were observed. Network analysis revealed 12 molecules involved in cancer, notably inhibition of cAMP. These novel tobacco-related biomarkers provide new insights to the effects of smoking which may be important in carcinogenesis but not previously linked with tobacco-related diseases. © 2016 Wiley Periodicals, Inc.

  17. Dioxins in cigarette smoke

    SciTech Connect

    Muto, H.; Takizawa, Y.

    1989-05-01

    Dioxins in cigarettes, smoke, and ash were determined using gas chromatography/mass spectrometry. The total concentration of polychlorinated dibenzo-p-dioxins (PCDDs) in cigarette smoke was approximately 5.0 micrograms/m3 at the maximum level, whereas various congeners from tetra-octa-chlorodibenzo-p-dioxin (-CDD) were detected. Particullary, the total concentration of hepta-CDD congeners was the highest among these congeners. Mass fragmentograms of various PCDD congeners were similar to those in flue gas samples collected from a municipal waste incinerator. The PCDD congeners that were not present in the cigarettes were found in the smoke samples. The 2,3,7,8-TCDD toxic equivalent value--an index for effects on humans--for total PCDDs in smoke was 1.81 ng/m3 using the toxic factor of the United States Environment Protection Agency. Daily intake of PCDDs by smoking 20 cigarettes was estimated to be approximately 4.3 pg.kg body weight/day. This value was close to that of the ADIs: 1-5 pg.kg body weight/day reported in several countries. A heretofore unrecognized health risk was represented by the presence of PCDDs in cigarette smoke.

  18. College Students' Perceptions of Risk and Addictiveness of E-Cigarettes and Cigarettes

    ERIC Educational Resources Information Center

    Cooper, Maria; Loukas, Alexandra; Harrell, Melissa B.; Perry, Cheryl L.

    2017-01-01

    Background: As conventional cigarette use is declining, electronic cigarette ("e-cigarette") use is rising and is especially high among college students. Few studies examine dual use of e-cigarettes and cigarettes among this population. This study explores the relationship between dual and exclusive e-cigarette / cigarette use and…

  19. E-Cigarettes (For Teens)

    MedlinePlus

    ... nicotine — a highly addictive drug — into your body. Electronic cigarettes are battery-powered smoking devices often designed ... an unhealthy dose of nicotine and other chemicals. Electronic cigarettes have been marketed to smokers as a ...

  20. E-Cigarettes (For Parents)

    MedlinePlus

    ... nicotine — a highly addictive drug — into the body. Electronic cigarettes are battery-powered smoking devices often designed ... an unhealthy dose of nicotine and other chemicals. Electronic cigarettes have been marketed to smokers as a ...

  1. E-Cigarettes (For Parents)

    MedlinePlus

    ... nicotine — a highly addictive drug — into the body. Electronic cigarettes are battery-powered smoking devices often designed to ... an unhealthy dose of nicotine and other chemicals. Electronic cigarettes have been marketed to smokers as a way ...

  2. E-Cigarettes (For Teens)

    MedlinePlus

    ... nicotine — a highly addictive drug — into your body. Electronic cigarettes are battery-powered smoking devices often designed to ... an unhealthy dose of nicotine and other chemicals. Electronic cigarettes have been marketed to smokers as a way ...

  3. Interplay between Smoking-induced Genotoxicity and Altered Signaling in Pancreatic Carcinogenesis

    PubMed Central

    Batra, Surinder K.

    2012-01-01

    Despite continuous research efforts directed at early diagnosis and treatment of pancreatic cancer (PC), the status of patients affected by this deadly malignancy remains dismal. Its notoriety with regard to lack of early diagnosis and resistance to the current chemotherapeutics is due to accumulating signaling abnormalities. Hoarding experimental and epidemiological evidences have established a direct correlation between cigarette smoking and PC risk. The cancer initiating/promoting nature of cigarette smoke can be attributed to its various constituents including nicotine, which is the major psychoactive component, and several other toxic constituents, such as nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and polycyclic aromatic hydrocarbons. These predominant smoke-constituents initiate a series of oncogenic events facilitating epigenetic alterations, self-sufficiency in growth signals, evasion of apoptosis, sustained angiogenesis, and metastasis. A better understanding of the molecular mechanisms underpinning these events is crucial for the prevention and therapeutic intervention against PC. This review presents various interconnected signal transduction cascades, the smoking-mediated genotoxicity, and genetic polymorphisms influencing the susceptibility for smoking-mediated PC development by modulating pivotal biological aspects such as cell defense/tumor suppression, inflammation, DNA repair, as well as tobacco-carcinogen metabolization. Additionally, it provides a large perspective toward tumor biology and the therapeutic approaches against PC by targeting one or several steps of smoking-mediated signaling cascades. PMID:22623649

  4. Cigarette smoking: an independent risk factor in alcoholic pancreatitis.

    PubMed

    Talamini, G; Bassi, C; Falconi, M; Frulloni, L; Di Francesco, V; Vaona, B; Bovo, P; Rigo, L; Castagnini, A; Angelini, G; Vantini, I; Pederzoli, P; Cavallini, G

    1996-03-01

    It is not known whether cigarette smoking plays a role as a risk factor in alcoholic pancreatitis. The aim of this study was to compare drinking and smoking habits in three groups of male subjects with an alcohol intake in excess of 40 g/day: (i) 67 patients with acute alcoholic pancreatitis, without other known potential causative agents; (ii) 396 patients with chronic alcoholic pancreatitis; and (iii) 265 control subjects randomly selected from the Verona polling lists and submitted to a complete medical checkup. The variables considered were age at onset of disease, years of drinking and smoking, daily alcohol intake in grams, number of cigarettes smoked daily, and body mass index (BMI). Cases differed from controls in daily grams of alcohol, number of cigarettes smoked and BMI (Mann-Whitney U test, p < 0.00001 for each comparison). Multivariate logistic regression analysis, comparing acute and chronic cases, respectively, versus controls, revealed an increased relative risk of pancreatitis in the two comparisons, associated in both cases with a higher alcohol intake (p < 0.00001) and cigarette smoking (p < 0.00001). No significant interaction between alcohol and smoking was noted, indicating that the two risks are independent. In conclusion, in males a higher number of cigarettes smoked daily seems to be a distinct risk factor in acute and chronic alcoholic pancreatitis.

  5. Training and cardiovascular responses from cigarette smoke exposure.

    PubMed

    de Sá, Felipe Gonçalves Dos Santos; da Mota, Gustavo Ribeiro; Sant'Ana, Paula Grippa; da Cunha, Márcia Regina Holanda; Marocolo, Moacir; Castardeli, Edson

    2014-12-31

    The aim of this study was to evaluate the early effect of the endurance training (ET) on systolic blood pressure (SBP), heart rate (HR) and rate pressure-product (RPP) after acute cigarette smoke exposure. Twenty male Wistar rats were randomly allocated into two groups: trained (TEx; n = 10) and control (CEx; n = 10), exposed to smoke. TEx rats undertook ET during 2 weeks (swimming, 5 days/week; 1 h/session) and CEx group was kept in sedentary lifestyle. After ET protocol both groups were exposed to cigarette smoke only once (total 1 h; 2 × 30 min with interval of 10 min between exposures; rate of 10 cigarettes/30 min). SBP, HR and RPP were measured after 2 weeks and just after (5 min) acute cigarette smoke (tail plethysmograph). All parameters did not differ (P > 0.05) between TEx (RPP = 45018 ± 1970 mmHg/bpm) and CEx (43695 ± 2579 mmHg/bpm) after ET protocol. However, all cardiovascular parameters increased (P < 0.05) only for CEx just after the cigarette smoke exposure. We concluded that ET can attenuate the aggression from acute smoking to cardiovascular system, with a few days of training and even with no chronic effect on these parameters at basal condition.

  6. A comparative assessment of cigarette smoke aerosols using an in vitro air–liquid interface cytotoxicity test

    PubMed Central

    Thorne, David; Dalrymple, Annette; Dillon, Deborah; Duke, Martin; Meredith, Clive

    2015-01-01

    Abstract This study describes the evaluation of a modified air-liquid interface BALB/c 3T3 cytotoxicity method for the assessment of smoke aerosols in vitro. The functionality and applicability of this modified protocol was assessed by comparing the cytotoxicity profiles from eight different cigarettes. Three reference cigarettes, 1R5F, 3R4F and CORESTA Monitor 7 were used to put the data into perspective and five bespoke experimental products were manufactured, ensuring a balanced and controlled study. Manufactured cigarettes were matched for key variables such as nicotine delivery, puff number, pressure drop, ventilation, carbon monoxide, nicotine free dry particulate matter and blend, but significantly modified for vapor phase delivery, via the addition of two different types and quantities of adsorptive carbon. Specifically manufacturing products ensures comparisons can be made in a consistent manner and allows the research to ask targeted questions, without confounding product variables. The results demonstrate vapor-phase associated cytotoxic effects and clear differences between the products tested and their cytotoxic profiles. This study has further characterized the in vitro vapor phase biological response relationship and confirmed that the biological response is directly proportional to the amount of available vapor phase toxicants in cigarette smoke, when using a Vitrocell® VC 10 exposure system. This study further supports and strengthens the use of aerosol based exposure options for the appropriate analysis of cigarette smoke induced responses in vitro and may be especially beneficial when comparing aerosols generated from alternative tobacco aerosol products. PMID:26339773

  7. The protective effect of melatonin on smoke-induced vascular injury in rats and humans: a randomized controlled trial.

    PubMed

    Wang, Zhanqi; Ni, Leng; Wang, Jing; Lu, Chengran; Ren, Meng; Han, Wei; Liu, Changwei

    2016-03-01

    Smoking is one of the most harmful lifestyles in the world. Very few studies have investigated the effects of melatonin in smoke-induced vascular injury. This study was designed to investigate whether melatonin could protect rats and humans from smoke-induced vascular injury. 32 male rats and a double-blind randomized controlled trial (RCT) containing 63 participants formed the subjects of this study. In rats, 10 mg/kg of melatonin was intraperitoneally injected. Blood samples and abdominal artery were harvested two weeks later. Melatonin decreased the expression of platelet endothelial cell adhesion molecule-1 (CD31), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) compared with the smoke exposed group (P < 0.05), whereas endothelial nitric oxide synthase (eNOS), nuclear erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO-1), catalytic glutamate cysteine ligase (GCLC) and heme oxygenase-1 (HO-1) recovered markedly (P < 0.05). In humans, 3 mg/day of melatonin was taken orally by the participants. Blood samples were drawn at baseline and after two weeks of treatment. Compared with the oral placebo group, melatonin decreased the concentration of fibrinogen (Fbg) (P = 0.04) and free fatty acids (FFA) (P = 0.04) in smokers, along with the decreased expression of ICAM-1, VCAM-1 and ET-1 (P = 0.004, P = 0.001, P < 0.0001, respectively). In contrast, Nrf2 and HO-1 expression were markedly increased (P = 0.0001, P = 0.0049, respectively) after smokers took melatonin orally. In summary, our present data suggest that melatonin could ameliorate smoke-induced vascular injury.

  8. Heavy Cigarette Smokers in a Chinese Population Display a Compromised Permeability Barrier

    PubMed Central

    Xin, Shujun; Ye, Li; Lv, Chengzhi; Elias, Peter M.

    2016-01-01

    Cigarette smoking is associated with various cutaneous disorders with defective permeability. Yet, whether cigarette smoking influences epidermal permeability barrier function is largely unknown. Here, we measured skin biophysical properties, including permeability barrier homeostasis, stratum corneum (SC) integrity, SC hydration, skin surface pH, and skin melanin/erythema index, in cigarette smokers. A total of 99 male volunteers were enrolled in this study. Smokers were categorized as light-to-moderate (<20 cigarettes/day) or heavy smokers (≥20 cigarettes/day). An MPA5 was used to measure SC hydration and skin melanin/erythema index on the dorsal hand, forehead, and cheek. Basal transepidermal water loss (TEWL) and barrier recovery rates were assessed on the forearm. A Skin-pH-Meter pH900 was used to measure skin surface pH. Our results showed that heavy cigarette smokers exhibited delayed barrier recovery after acute abrogation (1.02% ± 13.06 versus 16.48% ± 6.07), and barrier recovery rates correlated negatively with the number of daily cigarettes consumption (p = 0.0087). Changes in biophysical parameters in cigarette smokers varied with body sites. In conclusion, heavy cigarette smokers display compromised permeability barrier homeostasis, which could contribute, in part, to the increased prevalence of certain cutaneous disorders characterized by defective permeability. Thus, improving epidermal permeability barrier should be considered for heavy cigarette smokers. PMID:27437403

  9. Alternative Complement Pathway Deficiency Ameliorates Chronic Smoke-Induced Functional and Morphological Ocular Injury

    PubMed Central

    Woodell, Alex; Coughlin, Beth; Kunchithapautham, Kannan; Casey, Sarah; Williamson, Tucker; Ferrell, W. Drew; Atkinson, Carl; Jones, Bryan W.; Rohrer, Bärbel

    2013-01-01

    Background Age-related macular degeneration (AMD), a complex disease involving genetic variants and environmental insults, is among the leading causes of blindness in Western populations. Genetic and histologic evidence implicate the complement system in AMD pathogenesis; and smoking is the major environmental risk factor associated with increased disease risk. Although previous studies have demonstrated that cigarette smoke exposure (CE) causes retinal pigment epithelium (RPE) defects in mice, and smoking leads to complement activation in patients, it is unknown whether complement activation is causative in the development of CE pathology; and if so, which complement pathway is required. Methods Mice were exposed to cigarette smoke or clean, filtered air for 6 months. The effects of CE were analyzed in wildtype (WT) mice or mice without a functional complement alternative pathway (AP; CFB−/−) using molecular, histological, electrophysiological, and behavioral outcomes. Results CE in WT mice exhibited a significant reduction in function of both rods and cones as determined by electroretinography and contrast sensitivity measurements, concomitant with a thinning of the nuclear layers as measured by SD-OCT imaging and histology. Gene expression analyses suggested that alterations in both photoreceptors and RPE/choroid might contribute to the observed loss of function, and visualization of complement C3d deposition implies the RPE/Bruch's membrane (BrM) complex as the target of AP activity. RPE/BrM alterations include an increase in mitochondrial size concomitant with an apical shift in mitochondrial distribution within the RPE and a thickening of BrM. CFB−/− mice were protected from developing these CE-mediated alterations. Conclusions Taken together, these findings provide clear evidence that ocular pathology generated in CE mice is dependent on complement activation and requires the AP. Identifying animal models with RPE/BrM damage and verifying which

  10. Cigarette smoke extract induces aberrant cytochrome-c oxidase subunit II methylation and apoptosis in human umbilical vascular endothelial cells.

    PubMed

    Yang, Min; Chen, Ping; Peng, Hong; Zhang, Hongliang; Chen, Yan; Cai, Shan; Lu, Qianjin; Guan, Chaxiang

    2015-03-01

    Cigarette smoke-induced apoptosis of vascular endothelial cells contributes to the pathogenesis of chronic obstructive pulmonary disease. However, the mechanisms responsible for endothelial apoptosis remain poorly understood. We conducted an in vitro study to investigate whether DNA methylation is involved in smoking-induced endothelial apoptosis. Human umbilical vascular endothelial cells (HUVECs) were exposed to cigarette smoke extract (CSE) at a range of concentrations (0-10%). HUVECs were also incubated with a demethylating reagent, 5-aza-2'-deoxycytidinem (AZA), with and without CSE. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and flow cytometry using annexin V-FITC/propidium iodide staining. We found that CSE treatment significantly increased HUVEC apoptosis in a dose- and time-dependent manner. Quantitative real-time RT-PCR and immunoblot revealed that CSE treatment decreased cytochrome-c oxidase subunit II (COX II) mRNA and protein levels and decreased COX activity. Methylation-specific PCR and direct bisulfite sequencing revealed positive COX II gene methylation. AZA administration partly increased mRNA and protein expressions of COX II, and COX activity decreased by CSE and attenuated the toxic effects of CSE. Our results showed that CSE induced aberrant COX II methylation and apoptosis in HUVECs.

  11. Effect of a mucoactive compound (CO 1408) on airway hyperreactivity and inflammation induced by passive cigarette smoke exposure in guinea-pigs.

    PubMed

    Hernandez, A; Daffonchio, L; Brandolini, L; Zuccari, G

    1994-04-01

    Environmental exposure to tobacco smoke contributes to the onset of several lung diseases, e.g. chronic bronchitis and asthma, including an increase in airway reactivity. We have investigated the effect of a new mucoactive compound, CO 1408, on airway hyperreactivity and lung inflammation induced in guinea-pigs by passive cigarette smoke exposure. Animals were exposed to cigarette smoke in a Plexi-glass box, three times a day for four days. Airway reactivity to histamine was assessed ex-vivo in lung parenchymal strips. As a measure of lung inflammation, the number of leucocytes was evaluated in bronchoalveolar lavage (BAL) fluids and histological sections. Passive smoke exposure potentiated histamine-induced contraction in lung parenchymal strips, a phenomenon associated with an increase in proinflammatory cells in the BAL fluids and enhanced eosinophil infiltration into parenchymal tissues. Pretreatment with oral CO 1408 at 400 mg.kg-1 but not 100 mg.kg-1, completely prevented the cigarette smoke-induced airway hyperreactivity. 400 mg.kg-1 CO 1408 also inhibited the increase in cell numbers in the BAL fluids, but not eosinophil recruitment in parenchymal tissues. The present data indicate the ability of CO 1408 to modulate smoke-induced airway hyperreactivity and, to some extent, lung inflammation, an effect which might be of value in the therapy of obstructive pulmonary diseases.

  12. Electronic Cigarettes on Hospital Campuses

    PubMed Central

    Meernik, Clare; Baker, Hannah M.; Paci, Karina; Fischer-Brown, Isaiah; Dunlap, Daniel; Goldstein, Adam O.

    2015-01-01

    Smoke and tobacco-free policies on hospital campuses have become more prevalent across the U.S. and Europe, de-normalizing smoking and reducing secondhand smoke exposure on hospital grounds. Concerns about the increasing use of electronic cigarettes (e-cigarettes) and the impact of such use on smoke and tobacco-free policies have arisen, but to date, no systematic data describes e-cigarette policies on hospital campuses. The study surveyed all hospitals in North Carolina (n = 121) to assess what proportion of hospitals have developed e-cigarette policies, how policies have been implemented and communicated, and what motivators and barriers have influenced the development of e-cigarette regulations. Seventy-five hospitals (62%) completed the survey. Over 80% of hospitals reported the existence of a policy regulating the use of e-cigarettes on campus and roughly half of the hospitals without a current e-cigarette policy are likely to develop one within the next year. Most e-cigarette policies have been incorporated into existing tobacco-free policies with few reported barriers, though effective communication of e-cigarette policies is lacking. The majority of hospitals strongly agree that e-cigarette use on campus should be prohibited for staff, patients, and visitors. Widespread incorporation of e-cigarette policies into existing hospital smoke and tobacco-free campus policies is feasible but needs communication to staff, patients, and visitors. PMID:26729142

  13. Electronic Cigarettes on Hospital Campuses.

    PubMed

    Meernik, Clare; Baker, Hannah M; Paci, Karina; Fischer-Brown, Isaiah; Dunlap, Daniel; Goldstein, Adam O

    2015-12-29

    Smoke and tobacco-free policies on hospital campuses have become more prevalent across the U.S. and Europe, de-normalizing smoking and reducing secondhand smoke exposure on hospital grounds. Concerns about the increasing use of electronic cigarettes (e-cigarettes) and the impact of such use on smoke and tobacco-free policies have arisen, but to date, no systematic data describes e-cigarette policies on hospital campuses. The study surveyed all hospitals in North Carolina (n = 121) to assess what proportion of hospitals have developed e-cigarette policies, how policies have been implemented and communicated, and what motivators and barriers have influenced the development of e-cigarette regulations. Seventy-five hospitals (62%) completed the survey. Over 80% of hospitals reported the existence of a policy regulating the use of e-cigarettes on campus and roughly half of the hospitals without a current e-cigarette policy are likely to develop one within the next year. Most e-cigarette policies have been incorporated into existing tobacco-free policies with few reported barriers, though effective communication of e-cigarette policies is lacking. The majority of hospitals strongly agree that e-cigarette use on campus should be prohibited for staff, patients, and visitors. Widespread incorporation of e-cigarette policies into existing hospital smoke and tobacco-free campus policies is feasible but needs communication to staff, patients, and visitors.

  14. Advertising media and cigarette demand.

    PubMed

    Goel, Rajeev K

    2011-01-01

    Using state-level panel data for the USA spanning three decades, this research estimates the demand for cigarettes. The main contribution lies in studying the effects of cigarette advertising disaggregated across five qualitatively different groups. Results show cigarette demand to be near unit elastic, the income effects to be generally insignificant and border price effects and habit effects to be significant. Regarding advertising effects, aggregate cigarette advertising has a negative effect on smoking. Important differences across advertising media emerge when cigarette advertising is disaggregated. The effects of public entertainment and Internet cigarette advertising are stronger than those of other media. Anti-smoking messages accompanying print cigarette advertising seem relatively more effective. Implications for smoking control policy are discussed.

  15. Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

    NASA Astrophysics Data System (ADS)

    Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

    2014-03-01

    Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

  16. EFFECTS OF CONCURRENT OZONE EXPOSURE ON THE PATHOGENESIS OF CIGARETTE SMOKE-INDUCED EMPHYSEMA IN B6C3F1 MICE. (R826442)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  17. 27 CFR 40.352 - Cigarette tubes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Cigarette tubes. 40.352... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.352 Cigarette tubes. Cigarette...

  18. 27 CFR 40.352 - Cigarette tubes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Cigarette tubes. 40.352... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.352 Cigarette tubes. Cigarette...

  19. 27 CFR 40.352 - Cigarette tubes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Cigarette tubes. 40.352... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.352 Cigarette tubes. Cigarette...

  20. 27 CFR 40.352 - Cigarette tubes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Cigarette tubes. 40.352... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.352 Cigarette tubes. Cigarette...

  1. 27 CFR 40.352 - Cigarette tubes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Cigarette tubes. 40.352... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.352 Cigarette tubes. Cigarette...

  2. Cigarette smoke extract inhibits expression of peroxiredoxin V and increases airway epithelial permeability.

    PubMed

    Serikov, Vladimir B; Leutenegger, Christian; Krutilina, Raisa; Kropotov, Andrei; Pleskach, Nadezhda; Suh, Jung H; Tomilin, Nikolay V

    2006-01-01

    Inhaled cigarette smoke induces oxidative stress in the epithelium of airways. Peroxiredoxin V (PRXV) is a potent antioxidant protein, highly expressed in cells of the airway epithelium. The goal of our study was to determine whether cigarette smoke extract (CSE) influenced expression of this protein in airway epithelia in vivo and in vitro. In Sprague-Dawley rats, we determined effects of CSE on airway epithelial permeability, mRNA levels and expression of PRXV protein. Exposure of isolated tracheal segment in vitro to 20% CSE for 4 h resulted in development of increased permeability to albumin, significantly reduced mRNA levels for PRXV, and reduced amounts of PRXV protein in the epithelium. In cultures of the airway epithelial cell lines (Calu-3, JME), primary airway cell culture (cow), and alveolar epithelial cells A549, CSE also significantly decreased transepithelial electrical resistance and expression of PRXV protein, and induced glutathione and protein oxidation. To demonstrate functional importance of PRXV, we exposed clones of HeLa cells with siRNA-downregulated PRXV to hydrogen peroxide, which resulted in increased rate of cell death and protein oxidation. CSE directly downregulates expression of functionally important antioxidant enzyme PRXV in the epithelial cells of airways, which represents one pathophysiological mechanism of cigarette smoke toxicity.

  3. Exposure to cigarette smoke downregulates β2-adrenergic receptor expression and upregulates inflammation in alveolar macrophages.

    PubMed

    Wang, Wei; Li, Xiaoguang; Xu, Jie

    2015-01-01

    Cigarette smoke-triggered inflammation is important in the pathophysiology of chronic obstructive pulmonary disease (COPD). β2-Adrenergic receptor (β2-AR) is abundantly expressed on inflammatory cells, which is associated with inflammation regulation. To observe alterations in inflammation, pathological changes in lung tissues, and detect changes in β2-AR expression, rats were exposed for 4 months to cigarette smoke. Pathological changes were observed in lung tissue sections. The levels of inflammatory mediators tumor necrosis factor (TNF)-α, interleukin (IL)-1β in bronchoalveolar lavage fluid (BALF), and lung tissues were measured using enzyme-linked immunosorbent assay (ELISA). Nuclear factor (NF)-κB activity was detected by electrophoretic mobility shift assay (EMSA). Exposure to this regimen of cigarette smoke induced peribronchial and perivascular lymphocytic aggregates and parenchymal accumulation of macrophages in rats. EMSA demonstrated that smoke exposure enhanced NF-κB activation in rats' alveolar macrophages (AMs). Compared with the control group, smoke exposure induced a notable increase in TNF-α and IL-1β in BALF, lung tissues, and a decrease of β2-AR expression of AMs. The expression of β2-AR from AMs was inversely correlated with TNF-α and IL-1β levels of BALF. These data demonstrated that chronic smoke-triggered lung inflammation was accompanied by down-regulation of β2-AR in rat lungs' AMs.

  4. Increased Myeloid Cell Production and Lung Bacterial Clearance in Mice Exposed to Cigarette Smoke.

    PubMed

    Basilico, Paola; Cremona, Tiziana P; Oevermann, Anna; Piersigilli, Alessandra; Benarafa, Charaf

    2016-03-01

    Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most patients with COPD are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or after smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared with air-exposed mice when infected 16 to 24 hours after exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to levels comparable to those of control mice, suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production before infection in mice exposed to cigarette smoke with mice never exposed or after smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1β and granulocyte-macrophage colony-stimulating factor in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using Serpinb1a-deficient mice with reduced neutrophil numbers and treatment with granulocyte colony-stimulating factor showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow.

  5. Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity.

    PubMed

    Prasad, Shikha; Sajja, Ravi K; Kaisar, Mohammad Abul; Park, Jee Hyun; Villalba, Heidi; Liles, Taylor; Abbruscato, Thomas; Cucullo, Luca

    2017-02-12

    Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment. Our data in fact revealed that MF activates counteractive mechanisms primarily associated with the Nrf2 pathway which drastically reduce CS toxicity at the cerebrovascular level. These include the suppression of tight junction (TJ) protein downregulation and loss of BBB integrity induced by CS, reduction of inflammation and oxidative stress, renormalization of the expression levels of the major BBB glucose transporter Glut-1 and that of the anticoagulant factor thrombomodulin. Further, we provide additional insights on the controversial interplay between Nrf2 and AMPK.

  6. Tobacco smoke induces production of chemokine CCL20 to promote lung cancer.

    PubMed

    Wang, Gui-Zhen; Cheng, Xin; Li, Xin-Chun; Liu, Yong-Qiang; Wang, Xian-Quan; Shi, Xu; Wang, Zai-Yong; Guo, Yong-Qing; Wen, Zhe-Sheng; Huang, Yun-Chao; Zhou, Guang-Biao

    2015-07-10

    Tobacco kills nearly 6 million people each year, and 90% of the annual 1.59 million lung cancer deaths worldwide are caused by cigarette smoke. Clinically, a long latency is required for individuals to develop lung cancer since they were first exposed to smoking. In this study, we aimed to identify clinical relevant inflammatory factors that are critical for carcinogenesis by treating normal human lung epithelial cells with tobacco carcinogen nicotine-derived nitrosaminoketone (NNK) for a long period (60 days) and systematic screening in 84 cytokines/chemokines. We found that a chemokine CCL20 was significantly up-regulated by NNK, and in 78/173 (45.1%) patients the expression of CCL20 was higher in tumor samples than their adjacent normal lung tissues. Interestingly, CCL20 was up-regulated in 48/92 (52.2%) smoker and 29/78 (37.2%) nonsmoker patients (p = 0.05), and high CCL20 was associated with poor prognosis. NNK induced the production of CCL20, which promoted lung cancer cell proliferation and migration. In addition, an anti-inflammation drug, dexamethasone, inhibited NNK-induced CCL20 production and suppressed lung cancer in vitro and in vivo. These results indicate that CCL20 is crucial for tobacco smoke-caused lung cancer, and anti-CCL20 could be a rational approach to fight against this deadly disease.

  7. Cigarette Consumption and Cigarette Smoking Prevalence Among Adults in Kansas

    PubMed Central

    Lai, Sue Min

    2015-01-01

    Introduction Recent tobacco prevention and cessation activities have focused on nonsmoking ordinances and behavioral changes, and in Kansas, the overall prevalence of cigarette smoking among adults has decreased. The objective of this study was to determine whether overall cigarette consumption (mean annual number of cigarettes smoked) in Kansas also decreased. Methods Data on cigarette smoking prevalence for 91,465 adult Kansans were obtained from the Behavioral Risk Factor Surveillance System survey for 1999 through 2010. Data on annual cigarette consumption were obtained from the 2002 and 2006 Kansas Adult Tobacco Survey and analyzed by totals, by sex, and by smoking some days or smoking every day. Linear regression was used to evaluate rate changes over time. Results Among men, but not women, cigarette smoking prevalence decreased significantly over time. The prevalence of smoking every day decreased significantly among both men and women, whereas the prevalence of smoking on some days increased significantly for women but not men. For current smokers, the mean annual number of cigarettes consumed remained the same. Conclusion The decline in overall smoking prevalence coupled with the lack of change in mean annual cigarette consumption may have resulted in a more intense exposure to cigarettes for the smoking population. The significant increase in some day use among women indicates a need for additional prevention and education activities; the impact on future lung cancer incidence rates needs further investigation. PMID:26068414

  8. Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review.

    PubMed

    Palazzolo, Dominic L

    2013-11-18

    Electronic cigarette (e-cigarette) use, or vaping, in the United States and worldwide is increasing. Their use is highly controversial from scientific, political, financial, psychological, and sociological ideologies. Given the controversial nature of e-cigarettes and vaping, how should medical care providers advise their patients? To effectively face this new challenge, health care professionals need to become more familiar with the existing literature concerning e-cigarettes and vaping, especially the scientific literature. Thus, the aim of this article is to present a review of the scientific evidence-based primary literature concerning electronic cigarettes and vaping. A search of the most current literature using the pubmed database dating back to 2008, and using electronic cigarette(s) or e-cigarette(s) as key words, yielded a total of 66 highly relevant articles. These articles primarily deal with (1) consumer-based surveys regarding personal views on vaping, (2) chemical analysis of e-cigarette cartridges, solutions, and mist, (3) nicotine content, delivery, and pharmacokinetics, and (4) clinical and physiological studies investigating the effects of acute vaping. When compared to the effects of smoking, the scant available literature suggests that vaping could be a "harm reduction" alternative to smoking and a possible means for smoking cessation, at least to the same degree as other Food and Drug Administration-approved nicotine replacement therapies. However, it is unclear if vaping e-cigarettes will reduce or increase nicotine addiction. It is obvious that more rigorous investigations of the acute and long-term health effects of vaping are required to establish the safety and efficacy of these devices; especially parallel experiments comparing the cardiopulmonary effects of vaping to smoking. Only then will the medical community be able to adequately meet the new challenge e-cigarettes and vaping present to clinical medicine and public health.

  9. Electronic Cigarettes and Vaping: A New Challenge in Clinical Medicine and Public Health. A Literature Review

    PubMed Central

    Palazzolo, Dominic L.

    2013-01-01

    Electronic cigarette (e-cigarette) use, or vaping, in the United States and worldwide is increasing. Their use is highly controversial from scientific, political, financial, psychological, and sociological ideologies. Given the controversial nature of e-cigarettes and vaping, how should medical care providers advise their patients? To effectively face this new challenge, health care professionals need to become more familiar with the existing literature concerning e-cigarettes and vaping, especially the scientific literature. Thus, the aim of this article is to present a review of the scientific evidence-based primary literature concerning electronic cigarettes and vaping. A search of the most current literature using the pubmed database dating back to 2008, and using electronic cigarette(s) or e-cigarette(s) as key words, yielded a total of 66 highly relevant articles. These articles primarily deal with (1) consumer-based surveys regarding personal views on vaping, (2) chemical analysis of e-cigarette cartridges, solutions, and mist, (3) nicotine content, delivery, and pharmacokinetics, and (4) clinical and physiological studies investigating the effects of acute vaping. When compared to the effects of smoking, the scant available literature suggests that vaping could be a “harm reduction” alternative to smoking and a possible means for smoking cessation, at least to the same degree as other Food and Drug Administration-approved nicotine replacement therapies. However, it is unclear if vaping e-cigarettes will reduce or increase nicotine addiction. It is obvious that more rigorous investigations of the acute and long-term health effects of vaping are required to establish the safety and efficacy of these devices; especially parallel experiments comparing the cardiopulmonary effects of vaping to smoking. Only then will the medical community be able to adequately meet the new challenge e-cigarettes and vaping present to clinical medicine and public health. PMID

  10. Vascular effects of cigarette smoke in isolated pig lungs

    SciTech Connect

    Gilman, M.J.; Sylvester, J.T.; Kennedy, T.P.; Menkes, H.A.; Traystman, R.J.

    1981-11-01

    To determine the local effects of cigarette smoke on the pulmonary vasculature, we measured pulmonary artery pressure--flow curves in isolated, blood-perfused pig lungs before and after 4 exposures to cigarette smoke. During each exposure, smoke was administered into the trachea for 3 to 4 min at a rate of 20 to 25 puffs/min and a puff volume of 35 to 50 ml with a smoking machine. During hypoxia (inspired PO2, 50 mmHg), when baseline vasomotor tone was high, cigarette smoke caused an acute transient vasodilation. During control (inspired PO2, 200 mmHg), when baseline tone was low, no significant effect was observed. In addition to this acute effect, cigarette smoke caused a depression of the pulmonary pressor response to hypoxia, which developed gradually during the course of the experiment. Indomethacin, at perfusate concentrations of 20 and 100 micrograms/ml, did not significantly alter the acute vasodilating effect of smoking, suggesting that prostaglandins synthesized by cyclooxygenase were not the mediators of this response. Indomethacin did, however, prevent the gradual depression of the pulmonary vasoconstrictor response to hypoxia.

  11. Irritants in cigarette smoke plumes

    SciTech Connect

    Ayer, H.E.; Yeager, D.W.

    1982-11-01

    Concentrations of the irritants formaldehyde and acrolein in side stream cigarette smoke plumes are up to three orders of magnitude above occupational limits, readily accounting for eye and nasal irritation. ''Low-tar'' cigarettes appear at least as irritating as other cigarettes. More than half the irritant is associated with the particulate phase of the smoke, permitting deposition throughout the entire respiratory tract and raising the issue of whether formaldehyde in smoke is associated with bronchial cancer.

  12. 27 CFR 40.351 - Cigarette papers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.351 Cigarette papers....

  13. E-cigarettes and E-hookahs

    MedlinePlus

    Electronic cigarettes; Electronic hookahs; Vaping; Electronic nicotine delivery systems; Smoking - electronic cigarettes ... Elsevier Saunders; 2016:chap 46. Callahan-Lyon P. Electronic cigarettes: human health effects. Tob Control . 2014;23( ...

  14. Cigarette Smoking and Risk of Meningioma: The Effect of Gender

    PubMed Central

    Claus, Elizabeth B.; Walsh, Kyle M.; Calvocoressi, Lisa; Bondy, Melissa L.; Schildkraut, Joellen M.; Wrensch, Margaret; Wiemels, Joseph L.

    2013-01-01

    Background A number of studies have reported on the association between smoking and meningioma risk, with inconsistent findings. We examined the effect of gender on the association between cigarette smoking and risk of intra-cranial meningioma in a large population-based, case-control study. Methods The data includes 1433 intra-cranial meningioma cases aged 29–79 years diagnosed among residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area and eight Texas counties between May 1, 2006 and April 28, 2011 and 1349 controls that were frequency-matched on age, sex and geography. The data are analyzed separately and in a meta-analysis with six previously reported studies. Results Female cases who reported having ever smoked were at significantly decreased risk of intra-cranial meningioma (Odds ratio (OR) = 0.8, 95% confidence interval (CI), 0.7–0.9) in contrast to male cases who were at increased risk (OR:1.3, 95%CI: 1.0–1.7). Similar findings were noted for current and past smokers. Smoking-induced risk for females did not vary by menopausal status. For males, increased duration of use (p = 0.04) as well as increasing number of pack-years (p = 0.02) was associated with elevated risk. A meta-analysis including 2614 cases and 1,179,686 controls resulted in an OR for ever smoking of 0.82 (95%CI: 0.68–0.98) for women and 1.39 (95%CI: 1.08–1.79) for men. Conclusion The association of cigarette smoking and meningioma case status varies significantly by gender with women at reduced risk and men at greater risk. Impact Whether the observed differences are associated with a hormonal etiology will require additional investigation. PMID:22473761

  15. Functional small airways defence in symptomless cigarette smokers.

    PubMed Central

    Agnew, J E; Lopez-Vidriero, M T; Pavia, D; Clarke, S W

    1986-01-01

    Smoking induced changes in the secretory cells of bronchiolar epithelium by facilitating secretion of cross linked glycoprotein mucus may influence the efficiency of mucus-cilia coupling. The functional impact on mucociliary transport in small (peripheral) airways has been studied by comparing data on aerosol deposition and clearance from symptomless cigarette smokers (30 tests, 18 subjects) with data from age matched non-smokers (30 tests, 19 subjects). Gamma camera images, assessed in terms of a penetration index comparing peripheral with inner zone deposition, indicated closely similar initial deposition in the two groups. Alveolar deposition, however, assessed in terms of particle retention at 24 hours, was significantly (p less than 0.01) less in the smokers. Given the similarity of initial deposition, this implies that an increased proportion of small conducting airways are protected by mucociliary defence in the smokers' lungs. Clearance from conducting airways of the peripheral zone in tests with relatively high peripheral deposition (14 tests on smokers, and 12 on non-smokers) nevertheless proceeded at the same rate in smokers as in non-smokers. PMID:3787532

  16. The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition.

    PubMed

    Dawkins, Lynne; Turner, John; Hasna, Surrayyah; Soar, Kirstie

    2012-08-01

    Electronic cigarettes (e-cigarettes) are battery operated devices that deliver nicotine via inhaled vapour. Few studies have evaluated acute effects on craving and mood, and none have explored effects on cognition. This study aimed to explore the effects of the White Super e-cigarette on desire to smoke, nicotine withdrawal symptoms, attention and working memory. Eighty-six smokers were randomly allocated to either: 18 mg nicotine e-cigarette (nicotine), 0mg e-cigarette (placebo), or just hold the e-cigarette (just hold) conditions. Participants rated their desire to smoke and withdrawal symptoms at baseline (T1), and five (T2) and twenty (T3) minutes after using the e-cigarette ad libitum for 5 min. A subset of participants completed the Letter Cancellation and Brown-Peterson Working Memory Tasks. After 20 min, compared with the just hold group, desire to smoke and some aspects of nicotine withdrawal were significantly reduced in the nicotine and placebo group; the nicotine e-cigarette was superior to placebo in males but not in females. The nicotine e-cigarette also improved working memory performance compared with placebo at the longer interference intervals. There was no effect of nicotine on Letter Cancellation performance. To conclude, the White Super e-cigarette alleviated desire to smoke and withdrawal symptoms 20 min after use although the nicotine content was more important for males. This study also demonstrated for the first time that the nicotine e-cigarette can enhance working memory performance. Further evaluation of the cognitive effects of the e-cigarette and its efficacy as a cessation tool is merited.

  17. Chemical evaluation of electronic cigarettes

    PubMed Central

    Cheng, Tianrong

    2014-01-01

    Objective To review the available evidence evaluating the chemicals in refill solutions, cartridges, aerosols and environmental emissions of electronic cigarettes (e-cigarettes). Methods Systematic literature searches were conducted to identify research related to e-cigarettes and chemistry using 5 reference databases and 11 search terms. The search date range was January 2007 to September 2013. The search yielded 36 articles, of which 29 were deemed relevant for analysis. Results The levels of nicotine, tobacco-specific nitrosamines (TSNAs), aldehydes, metals, volatile organic compounds (VOCs), flavours, solvent carriers and tobacco alkaloids in e-cigarette refill solutions, cartridges, aerosols and environmental emissions vary considerably. The delivery of nicotine and the release of TSNAs, aldehydes and metals are not consistent across products. Furthermore, the nicotine level listed on the labels of e-cigarette cartridges and refill solutions is often significantly different from measured values. Phenolic compounds, polycyclic aromatic hydrocarbons and drugs have also been reported in e-cigarette refill solutions, cartridges and aerosols. Varying results in particle size distributions of particular matter emissions from e-cigarettes across studies have been observed. Methods applied for the generation and chemical analyses of aerosols differ across studies. Performance characteristics of e-cigarette devices also vary across and within brands. Conclusions Additional studies based on knowledge of e-cigarette user behaviours and scientifically validated aerosol generation and chemical analysis methods would be helpful in generating reliable measures of chemical quantities. This would allow comparisons of e-cigarette aerosol and traditional smoke constituent levels and would inform an evaluation of the toxicity potential of e-cigarettes. PMID:24732157

  18. Successful and not so successful chemoprevention of tobacco smoke-induced lung tumors.

    PubMed

    Witschi, H

    2000-12-01

    Strain A/J mice underwent whole body exposure for 6 hours a day, 5 days a week, for 5 months to a mixture of cigarette sidestream and mainstream smoke (89%-11%; total suspended particulates 80-150 mg/m3), then were kept for another 4 months in air before being killed for scoring of lung tumors. In 7 independent experiments, lung tumor multiplicity was significantly increased in all 7 trials and lung tumor incidence in 5. When animals were kept for 9 months in smoke, lung tumor multiplicity was not significantly higher than in controls, although lung tumor incidence was. The following chemopreventive agents were evaluated: green tea, phenethyl isothiocyanate (PEITC), acetylsalicylic acid (ASA), N-acetylcysteine (NAC), p-XSC (1,4-phenylenebis[methylene]selenocyanate), d-limonene (DL), and a mixture of PEITC and BITC (benzyl isothiocyanate). In animals exposed to tobacco smoke, none of these agents reduced lung tumor multiplicity or incidence. As a control, the effects of the same agents were examined in A/J mice initiated with 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK) or urethane. In mice injected with NNK, green tea and ASA did not reduce lung tumor multiplicities and NAC had no effect on urethane-induced lung tumors, whereas PEITC, p-XSC and DL reduced NNK-induced tumor multiplicities to 20% to 50% of control values. On the other hand, dietary mixture of myoinositol and dexamethasone was not only highly protective against NNK, but reduced lung tumor multiplicities and incidence in smoke-exposed animals to control values. This effect was also seen when the animals were fed the myo-inositol-dexamethasone mixture once they were removed from smoke. It is concluded that in animal studies it might be preferable to evaluate the effectiveness of putative chemopreventive agents against full tobacco smoke rather than against selected model compounds. The observations made with myo-inositol-dexamethasone suggest that people who have recently quit smoking might

  19. Up-Regulation of Claudin-6 in the Distal Lung Impacts Secondhand Smoke-Induced Inflammation

    PubMed Central

    Lewis, Joshua B.; Milner, Dallin C.; Lewis, Adam L.; Dunaway, Todd M.; Egbert, Kaleb M.; Albright, Scott C.; Merrell, Brigham J.; Monson, Troy D.; Broberg, Dallin S.; Gassman, Jason R.; Thomas, Daniel B.; Arroyo, Juan A.; Reynolds, Paul R.

    2016-01-01

    It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung. Cldn6 transgenic (TG) and control mice were continuously provided doxycycline from postnatal day (PN) 30 until euthanasia date at PN90. A subset of Cldn6 TG and control mice were also subjected to daily secondhand tobacco smoke (SHS) via a nose only inhalation system from PN30-90 and compared to room air (RA) controls. Animals were euthanized on PN90 and lungs were harvested for histological and molecular characterization. Bronchoalveolar lavage fluid (BALF) was procured for the assessment of inflammatory cells and molecules. Quantitative RT-PCR and immunoblotting revealed increased Cldn6 expression in TG vs. control animals and SHS decreased Cldn6 expression regardless of genetic up-regulation. Histological evaluations revealed no adverse pulmonary remodeling via Hematoxylin and Eosin (H&E) staining or any qualitative alterations in the abundance of type II pneumocytes or proximal non-ciliated epithelial cells via staining for cell specific propeptide of Surfactant Protein-C (proSP-C) or Club Cell Secretory Protein (CCSP), respectively. Immunoblotting and qRT-PCR confirmed the differential expression of Cldn6 and the pro-inflammatory cytokines TNF-α and IL-1β. As a general theme, inflammation induced by SHS exposure was influenced by the availability of Cldn6. These data reveal captivating

  20. Effects of omega-3 fatty acids on tobacco craving in cigarette smokers: A double-blind, randomized, placebo-controlled pilot study.

    PubMed

    Rabinovitz, Sharon

    2014-08-01

    Cigarette smoke induces oxidative stress with subsequent polyunsaturated fatty acids (PUFAs) peroxidation. Low concentrations of omega-3 PUFAs can affect neurotransmission, resulting in hypofunctioning of the mesocortical systems associated with reward and dependence mechanisms and thus may increase cigarette craving, hampering smoking cessation efforts. PUFA deficiency, in particular eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3), has also been linked to reduced psychological health and ability to cope with stress. Although stress is well linked to smoking urges and behavior, no research to date has examined the effects of PUFA supplementation on tobacco craving. In this double-blind, randomized, placebo-controlled pilot study, performed in regular cigarette smokers (n=48), administration of 2710 mg EPA/day and 2040 mg DHA/day for one month was accompanied by a significant decrease in reported daily smoking and in tobacco craving following cigarette cue exposure. Craving did not return to baseline values in the month that followed treatment discontinuation. This is the first study demonstrating that omega-3 PUFA supplementation reduces tobacco craving in regular smokers, compared to placebo treatment. Thus, omega-3 PUFAs may be of benefit in managing tobacco consumption. Further studies are needed on larger samples to explore the possible therapeutic implications for heavy cigarette smokers.

  1. Electronic cigarettes in the media

    PubMed Central

    Orellana-Barrios, Menfil; Medrano-Juarez, Rita; Buscemi, Dolores; Nugent, Kenneth

    2016-01-01

    Electronic cigarettes (e-cigarettes) are an increasingly popular source of nicotine and an increasingly popular topic in the media. Concerns about potential hazards associated with e-cigarette use and advertising, especially to adolescents, have led to studies on e-cigarettes in both traditional media (TV, mail, print, and outdoor advertising) and social media (websites, social networking sites, blogs, and e-mails). This review presents a narrative description of available studies related to e-cigarettes in the media. These articles have focused on promotion in both traditional and social media across a broad range of topics and have concentrated on target audiences, smoking cessation, harm reduction, and advertising. E-cigarette advertising is the most frequent topic in the published articles. Identifying the target audience also is a common objective in articles. The representation of e-cigarettes as a “healthier alternative” to traditional cigarettes and their use as a “smoking cessation aid” are main themes presented through all types of media. PMID:27365871

  2. France acts on electronic cigarettes.

    PubMed

    Cahn, Zachary

    2013-11-01

    France is deciding how to regulate electronic cigarettes. I first consider the French approach and how it contrasts with other attempts at electronic cigarette regulation globally. Next, I critique the individual elements of the French proposal. The overall approach taken by France is a positive development, but banning indoor use appears unnecessary and banning advertising may be counterproductive.

  3. Anti-cyclic citrullinated peptide (CCP) antibody in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) without rheumatoid arthritis.

    PubMed

    Sigari, Naseh; Moghimi, Nasrin; Shahraki, Farhad Saber; Mohammadi, Shilan; Roshani, Daem

    2015-01-01

    Citrullination, a post-translational modification of proteins, is increased in inflammatory processes and is known to occur in smokers. It can induce anti-cyclic citrullinated peptide (CCP) antibodies, the most specific serologic marker for rheumatoid arthritis. Thus far, the incidence of autoimmunity in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) resulting in anti-CCP production has not been examined. We hypothesise that anti-CCP antibody level in these patients should be higher than that in healthy subjects. A total of 112 non-rheumatoid arthritis patients, including 56 patients with wood-smoke-induced COPD and 56 patients with tobacco-induced COPD, and 56 healthy non-smoker controls were included. The serum anti-CCP antibody levels were measured and compared between the groups and against smoke exposure and clinical characteristics. The mean anti-CCP antibody levels in wood-smoke-induced COPD group were significantly higher than those in tobacco-induced COPD group (p = 0.03) and controls (p = 0.004). Furthermore, 8 (14.2 %) patients with wood-smoke-induced COPD, 4 (7.14 %) with tobacco-induced COPD and 2 (3.57 %) controls exceeded the conventional cut-off of anti-CCP antibody positivity. No relationship was found between the anti-CCP antibody level and age, gender, duration of disease, Pack-years of smoking, and duration of exposure to wood smoke. Moreover, correlations between anti-CCP antibodies and severity of airflow limitation, CAT scores, mMRC scores of dyspnoea, and GOLD staging of COPD severity were not significant. Wood-smoke-induced COPD could significantly increase the anti-CCP antibody level in non-rheumatoid arthritis patients when compared with that in patients with tobacco-induced COPD and healthy controls.

  4. Cigarette Smoking in Iran

    PubMed Central

    Meysamie, A; Ghaletaki, R; Zhand, N; Abbasi, M

    2012-01-01

    Background: Cigarette smoking is the largest preventable cause of death worldwide. No systematic review is available on the situation of the smoking in Iran, so we decided to provide an overview of the studies in the field of smoking in Iranian populations. Methods: Published Persian-language papers of all types until 2009 indexed in the IranMedex (http://www.iranmedex.com) and Magiran (http://www.magiran.com). Reports of World Health Organization were also searched and optionally employed. The studies concerning passive smoking or presenting the statistically insignificant side effects were excluded. Databases were searched using various combinations of the following terms: cigarette, smoking, smoking cessation, prevalence, history, side effects, and lung cancer by independent reviewers. All the 83 articles concerning the prevalence or side effects of the smoking habit in any Iranian population were selected. The prevalence rate of daily cigarette smoking and the 95% confidence interval as well as smoking health risk associated odds ratio (OR) were retrieved from the articles or calculated. Results: The reported prevalence rates of the included studies, the summary of smoking-related side effects and the ORs (95%CI) of smoking associated risks and the available data on smoking cessation in Iran have been shown in the article. Conclusion: Because of lack of certain data, special studies on local pattern of tobacco use in different districts, about the relationship between tobacco use and other diseases, especially non communicable diseases, and besides extension of smoking cessation strategies, studies on efficacy of these methods seems to be essential in this field. PMID:23113130

  5. Electronic Cigarettes: Vulnerability of Youth

    PubMed Central

    2015-01-01

    Electronic cigarettes have become popular and are heavily promoted as a safer cigarette and an aid to quit smoking. Although they may have value in reducing cigarette use among smokers, they are of limited value in smoking cessation and pose many problems, particularly in children. Nicotine is highly addictive and affects virtually all cells in the body. It is particularly harmful to developing brains and other organs. The electronic nicotine delivery systems are largely uncontrolled and safety risks are manifold. Initiating nicotine use and increasing dependence in the population may be linked with increased tobacco and other addictive substance abuse even if the individual electronic cigarette delivers less harm than a combustible cigarette does. PMID:25830075

  6. Receptivity to E-cigarette Marketing, Harm Perceptions, and E-cigarette Use

    PubMed Central

    Pokhrel, Pallav; Fagan, Pebbles; Kehl, Lisa; Herzog, Thaddeus A.

    2016-01-01

    Objective To test whether exposure and receptivity to e-cigarette marketing are associated with recent e-cigarette use among young adults through increased beliefs that e-cigarettes are less harmful than cigarettes. Methods Data were collected from 307 multiethnic 4- and 2-year college students; approximately equal proportions of current, never, and former cigarette smokers [mean age = 23.5 (SD = 5.5); 65% female]. Results Higher receptivity to e-cigarette marketing was associated with perceptions that e-cigarettes are less harmful than cigarettes, which in turn, were associated with higher recent e-cigarette use. Conclusions The findings provide preliminary support to the proposition that marketing of e-cigarettes as safer alternatives to cigarettes or cessation aids is associated with increased e-cigarette use among young adults. The findings have implications for development of e-cigarette regulations. PMID:25290604

  7. Cigarette Smoking and Electronic Cigarettes Use: A Meta-Analysis.

    PubMed

    Wang, Meng; Wang, Jian-Wei; Cao, Shuang-Shuang; Wang, Hui-Qin; Hu, Ru-Ying

    2016-01-12

    Increasing evidence indicates that cigarette smoking is a strong predictor of electronic cigarettes (e-cigarettes) use, particularly in adolescents, yet the effects has not be systematically reviewed and quantified. Relevant studies were retrieved by searching three databases up to June 2015. The meta-analysis results were presented as pooled odds ratios (ORs) with 95% confidence intervals (CIs) calculated by a random-effects model. Current smokers were more likely to use e-cigarette currently (OR: 14.89, 95% CI: 7.70-28.78) and the probability was greater in adolescents than in adults (39.13 vs. 7.51). The probability of ever e-cigarettes use was significantly increased in smokers (OR: 14.67, 95% CI: 11.04-19.49). Compared with ever smokers and adults, the probabilities were much greater in current smokers (16.10 vs. 9.47) and adolescents (15.19 vs. 14.30), respectively. Cigarette smoking increases the probability of e-cigarettes use, especially in current smokers and adolescents.

  8. Cigarette Smoking and Electronic Cigarettes Use: A Meta-Analysis

    PubMed Central

    Wang, Meng; Wang, Jian-Wei; Cao, Shuang-Shuang; Wang, Hui-Qin; Hu, Ru-Ying

    2016-01-01

    Increasing evidence indicates that cigarette smoking is a strong predictor of electronic cigarettes (e-cigarettes) use, particularly in adolescents, yet the effects has not be systematically reviewed and quantified. Relevant studies were retrieved by searching three databases up to June 2015. The meta-analysis results were presented as pooled odds ratios (ORs) with 95% confidence intervals (CIs) calculated by a random-effects model. Current smokers were more likely to use e-cigarette currently (OR: 14.89, 95% CI: 7.70–28.78) and the probability was greater in adolescents than in adults (39.13 vs. 7.51). The probability of ever e-cigarettes use was significantly increased in smokers (OR: 14.67, 95% CI: 11.04–19.49). Compared with ever smokers and adults, the probabilities were much greater in current smokers (16.10 vs. 9.47) and adolescents (15.19 vs. 14.30), respectively. Cigarette smoking increases the probability of e-cigarettes use, especially in current smokers and adolescents. PMID:26771624

  9. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    PubMed

    Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

    2012-01-01

    Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  10. Variation in, and causes of, toxicity of cigarette butts to a cladoceran and microtox.

    PubMed

    Micevska, T; Warne, M St J; Pablo, F; Patra, R

    2006-02-01

    Cigarette butts are the most numerically frequent form of litter in the world. In Australia alone, 24-32 billion cigarette butts are littered annually. Despite this littering, few studies have been undertaken to explore the toxicity of cigarette butts in aquatic ecosystems. The acute toxicity of 19 filtered cigarette types to Ceriodaphnia cf. dubia (48-hr EC50 (immobilization)) and Vibrio fischeri (30-min EC50 (bioluminescence)) was determined using leachates from artificially smoked cigarette butts. There was a 2.9- and 8-fold difference in toxicity between the least and most toxic cigarette butts to C. cf. dubia and V. fischeri, respectively. Overall, C. cf. dubia was more inherently sensitive than V. fischeri by a factor of approximately 15.4, and the interspecies relationship between C. cf. dubia and V. fischeri was poor (R(2) = 0.07). This poor relationship indicates that toxicity data for cigarette butts for one species could not predict or model the toxicity of cigarette butts to the other species. However, the order of the toxicity of leachates can be predicted. It was determined that organic compounds caused the majority of toxicity in the cigarette butt leachates. Of the 14 organic compounds identified, nicotine and ethylphenol were suspected to be the main causative toxicants. There was a strong relationship between toxicity and tar content and between toxicity and nicotine content for two of the three brands of cigarettes (R(2 )> 0.70) for C. cf. dubia and one brand for V. fischeri. However, when the cigarettes were pooled, the relationship was weak (R(2) < 0.40) for both test species. Brand affected the toxicity to both species but more so for V. fischeri.

  11. 19 CFR 159.5 - Cigars, cigarettes, and cigarette papers and tubes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Cigars, cigarettes, and cigarette papers and tubes..., and cigarette papers and tubes. The internal revenue taxes imposed on cigars, cigarettes, and cigarette papers and tubes under section 5701 or 7652, Internal Revenue Code of 1954 (26 U.S.C. 5701 or...

  12. 19 CFR 159.5 - Cigars, cigarettes, and cigarette papers and tubes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Cigars, cigarettes, and cigarette papers and tubes..., and cigarette papers and tubes. The internal revenue taxes imposed on cigars, cigarettes, and cigarette papers and tubes under section 5701 or 7652, Internal Revenue Code of 1954 (26 U.S.C. 5701 or...

  13. 19 CFR 159.5 - Cigars, cigarettes, and cigarette papers and tubes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Cigars, cigarettes, and cigarette papers and tubes..., and cigarette papers and tubes. The internal revenue taxes imposed on cigars, cigarettes, and cigarette papers and tubes under section 5701 or 7652, Internal Revenue Code of 1954 (26 U.S.C. 5701 or...

  14. 19 CFR 159.5 - Cigars, cigarettes, and cigarette papers and tubes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Cigars, cigarettes, and cigarette papers and tubes..., and cigarette papers and tubes. The internal revenue taxes imposed on cigars, cigarettes, and cigarette papers and tubes under section 5701 or 7652, Internal Revenue Code of 1954 (26 U.S.C. 5701 or...

  15. 19 CFR 159.5 - Cigars, cigarettes, and cigarette papers and tubes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Cigars, cigarettes, and cigarette papers and tubes..., and cigarette papers and tubes. The internal revenue taxes imposed on cigars, cigarettes, and cigarette papers and tubes under section 5701 or 7652, Internal Revenue Code of 1954 (26 U.S.C. 5701 or...

  16. Combined alpha-tocopherol and ascorbic acid protects against smoke-induced lung squamous metaplasia in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many epidemiological studies show the benefit of fruits and vegetables on reducing risk of lung cancer, the leading cause of cancer death in the United States. Previously, we demonstrated that cigarette smoke exposure (SM)-induced lung lesions in ferrets were prevented by a combination of carotene,...

  17. 27 CFR 40.351 - Cigarette papers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Cigarette papers. 40.351... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.351 Cigarette papers....

  18. 27 CFR 41.34 - Cigarette papers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Cigarette papers. 41.34... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.34 Cigarette papers. Cigarette papers are taxed at the...

  19. 27 CFR 41.34 - Cigarette papers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Cigarette papers. 41.34... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.34 Cigarette papers. Cigarette papers are taxed at the...

  20. 27 CFR 40.351 - Cigarette papers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Cigarette papers. 40.351... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.351 Cigarette papers....

  1. Functional Analysis and Treatment of Cigarette Pica.

    ERIC Educational Resources Information Center

    Piazza, Cathleen C.; And Others

    1996-01-01

    This study of an adolescent with mental retardation and autism found that pica of cigarette butts was maintained in a condition with no social consequences when cigarettes contained nicotine but not when cigarettes contained herbs without nicotine. A procedure based on stimulus control, which reduced cigarette consumption to zero, is described.…

  2. 27 CFR 41.34 - Cigarette papers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Cigarette papers. 41.34... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.34 Cigarette papers. Cigarette papers are taxed at the...

  3. 27 CFR 41.34 - Cigarette papers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Cigarette papers. 41.34... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.34 Cigarette papers. Cigarette papers are taxed at the...

  4. 27 CFR 40.351 - Cigarette papers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Cigarette papers. 40.351... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.351 Cigarette papers....

  5. 27 CFR 41.38 - Cigarettes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Cigarettes. 41.38 Section... THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Classification of Large Cigars and Cigarettes § 41.38 Cigarettes. For...

  6. 27 CFR 41.38 - Cigarettes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Cigarettes. 41.38 Section... THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Classification of Large Cigars and Cigarettes § 41.38 Cigarettes. For...

  7. 27 CFR 41.38 - Cigarettes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Cigarettes. 41.38 Section... THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Classification of Large Cigars and Cigarettes § 41.38 Cigarettes. For...

  8. 27 CFR 41.34 - Cigarette papers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Cigarette papers. 41.34... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.34 Cigarette papers. Cigarette papers are taxed at the...

  9. 27 CFR 40.351 - Cigarette papers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Cigarette papers. 40.351... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.351 Cigarette papers....

  10. 27 CFR 41.38 - Cigarettes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Cigarettes. 41.38 Section... THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Classification of Large Cigars and Cigarettes § 41.38 Cigarettes. For...

  11. 27 CFR 41.38 - Cigarettes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Cigarettes. 41.38 Section... THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Classification of Large Cigars and Cigarettes § 41.38 Cigarettes. For...

  12. 27 CFR 41.35 - Cigarette tubes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Cigarette tubes. 41.35... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes are taxed at the following...

  13. 27 CFR 41.35 - Cigarette tubes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Cigarette tubes. 41.35... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes are taxed at the following...

  14. 27 CFR 41.35 - Cigarette tubes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Cigarette tubes. 41.35... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes are taxed at the following...

  15. 27 CFR 41.35 - Cigarette tubes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Cigarette tubes. 41.35... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes are taxed at the following...

  16. 27 CFR 41.35 - Cigarette tubes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Cigarette tubes. 41.35... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes are taxed at the following...

  17. NF-{kappa}B inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats

    SciTech Connect

    Zhong Caiyun; Zhou Yamei; Pinkerton, Kent E.

    2008-07-15

    Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-{kappa}B) in this process. Exposure of rats to 80 mg/m{sup 3} tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-{kappa}B activity, noted by suppression of inhibitor of {kappa}B (I{kappa}B) kinase (IKK), accumulation of I{kappa}B{alpha}, decrease of NF-{kappa}B DNA binding activity, and downregulation of NF-{kappa}B-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-{kappa}B pathway in tobacco smoke-induced apoptosis.

  18. Effect of hydrogen injected subcutaneously on testicular tissues of rats exposed to cigarette smoke

    PubMed Central

    Chen, Song; Jiang, Wei

    2015-01-01

    Smoking is one of the most common reasons inducing reactive oxygen species in semen. High concentration of active oxygen will cause decrease of sperm density and viability and induce oxidative injury of sperm DNA which has become the hot spot in male infertility. Although hydrogen was found to be an effective remover of active oxygen in liver, heart, kidney and brain, the same effect has not been discussed in reproductive system. The aim of this study was to investigate the protective effect of hydrogen against cigarette smoke-induced damage in rat reproductive system. Adult male Wistar rats were randomly divided into four groups to conduct this experiment, results showed that rats in SK+HSI group (passive smoking and hydrogen subcutaneous injection group) exhibited larger amount of sperm count, smaller sperm deformation rate, higher levels of testosterone and SOD in serum and testis, lower levels of MDA in testis and less morphologic abnormalities compared to SK+NSI group (passive smoking and nitrogen subcutaneous injection group). As a consequence, we concluded that injected subcutaneously exerted protective effects on reproductive system injury of male rats exposed to cigarette smoke through inhibiting oxidative damage. PMID:26131139

  19. Marketing of menthol cigarettes and consumer perceptions

    PubMed Central

    2011-01-01

    In order to more fully understand why individuals smoke menthol cigarettes, it is important to understand the perceptions held by youth and adults regarding menthol cigarettes. Perceptions are driven by many factors, and one factor that can be important is marketing. This review seeks to examine what role, if any, the marketing of menthol cigarettes plays in the formation of consumer perceptions of menthol cigarettes. The available literature suggests that menthol cigarettes may be perceived as safer choices than non-menthol cigarettes. Furthermore, there is significant overlap between menthol cigarette advertising campaigns and the perceptions of these products held by consumers. The marketing of menthol cigarettes has been higher in publications and venues whose target audiences are Blacks/African Americans. Finally, there appears to have been changes in cigarette menthol content over the past decade, which has been viewed by some researchers as an effort to attract different types of smokers. PMID:21624148

  20. Expectancies for Cigarettes, E-Cigarettes, and Nicotine Replacement Therapies Among E-Cigarette Users (aka Vapers)

    PubMed Central

    Marquinez, Nicole S.; Correa, John B.; Meltzer, Lauren R.; Unrod, Marina; Sutton, Steven K.; Simmons, Vani N.; Brandon, Thomas H.

    2015-01-01

    Introduction: Use of e-cigarettes has been increasing exponentially, with the primary motivation reported as smoking cessation. To understand why smokers choose e-cigarettes as an alternative to cigarettes, as well as to US Food and Drug Administration (FDA)–approved nicotine replacement therapies (NRT), we compared outcome expectancies (beliefs about the results of drug use) for the three nicotine delivery systems among vapers, i.e., e-cigarette users, who were former smokers. Methods: Vapers (N = 1,434) completed an online survey assessing 14 expectancy domains as well as perceived cost and convenience. We focused on comparisons between e-cigarettes and cigarettes to determine the attraction of e-cigarettes as a smoking alternative and between e-cigarettes and NRT to determine perceived advantages of e-cigarettes over FDA-approved pharmacotherapy. Results: Participants believed that e-cigarettes, in comparison to conventional cigarettes, had fewer health risks; caused less craving, withdrawal, addiction, and negative physical feelings; tasted better; and were more satisfying. In contrast, conventional cigarettes were perceived as better than e-cigarettes for reducing negative affect, controlling weight, providing stimulation, and reducing stress. E-cigarettes, compared to NRT, were perceived to be less risky, cost less, cause fewer negative physical feelings, taste better, provide more satisfaction, and be better at reducing craving, negative affect, and stress. Moderator analyses indicated history with ad libitum forms of NRT was associated with less positive NRT expectancies. Conclusions: The degree to which expectancies for e-cigarettes differed from expectancies for either tobacco cigarettes or NRT offers insight into the motivation of e-cigarette users and provides guidance for public health and clinical interventions to encourage smoking-related behavior change. PMID:25168035

  1. Cigarette smoke extract profoundly suppresses TNFα-mediated proinflammatory gene expression through upregulation of ATF3 in human coronary artery endothelial cells

    PubMed Central

    Teasdale, Jack E.; Hazell, Georgina G. J.; Peachey, Alasdair M. G.; Sala-Newby, Graciela B.; Hindmarch, Charles C. T.; McKay, Tristan R.; Bond, Mark; Newby, Andrew C.; White, Stephen J.

    2017-01-01

    Endothelial dysfunction caused by the combined action of disturbed flow, inflammatory mediators and oxidants derived from cigarette smoke is known to promote coronary atherosclerosis and increase the likelihood of myocardial infarctions and strokes. Conversely, laminar flow protects against endothelial dysfunction, at least in the initial phases of atherogenesis. We studied the effects of TNFα and cigarette smoke extract on human coronary artery endothelial cells under oscillatory, normal laminar and elevated laminar shear stress for a period of 72 hours. We found, firstly, that laminar flow fails to overcome the inflammatory effects of TNFα under these conditions but that cigarette smoke induces an anti-oxidant response that appears to reduce endothelial inflammation. Elevated laminar flow, TNFα and cigarette smoke extract synergise to induce expression of the transcriptional regulator activating transcription factor 3 (ATF3), which we show by adenovirus driven overexpression, decreases inflammatory gene expression independently of activation of nuclear factor-κB. Our results illustrate the importance of studying endothelial dysfunction in vitro over prolonged periods. They also identify ATF3 as an important protective factor against endothelial dysfunction. Modulation of ATF3 expression may represent a novel approach to modulate proinflammatory gene expression and open new therapeutic avenues to treat proinflammatory diseases. PMID:28059114

  2. Cigarette smoking in China: public health, science, and policy.

    PubMed

    Au, William W; Su, Daisy; Yuan, Jiang

    2012-01-01

    Throughout the world, cigarette smoking is a habit that causes serious health, economic, and social problems. Therefore, many countries have taken an active role to control and to ban smoking. The chronic smoking problem in China is particularly acute because China has the largest population of smokers in the world, over 300 million currently. If 30% of these smokers were to die of smoke-related diseases in the next 20 years, the impact from the more than 90 million premature deaths could be damaging to China. In addition, numerous non-smokers also experience health problems from exposure to environmental tobacco smoke. China's efforts to reduce or to ban smoking in certain public places have not been well-coordinated or enforced compared with those in other countries. Therefore, success has been minimal. Consequently, leaders in China should not be complacent about combating the serious national health problem. A multiprong approach in combination with the MPOWER policy from the World Health Organization that targets different levels of acquisition of the smoking habit must be used. Examples may include the government's reduced reliance on profits from the sale of cigarettes, the elimination of advertisements that encourage smoking among young individuals, the presentation of more graphic illustration of harmful effects from smoking on every pack of cigarettes, higher taxes/prices on cigarettes, and the implementation of enforceable bans on smoking in public places. As shown in other countries, such coordinated effort can be highly effective in the reduction of smoking and can have healthy consequences.

  3. Sex-Related Cochlear Impairment in Cigarette Smokers

    PubMed Central

    Lisowska, Grażyna; Jochem, Jerzy; Gierlotka, Agata; Misiołek, Maciej; Ścierski, Wojciech

    2017-01-01

    Background A number of studies have documented the influence of cigarette smoking on hearing. However, the association between sex and hearing impairment in smokers as measured by otoacoustic emissions (OAEs) has not been clearly established. The aim of this study was to analyze sex-specific effects of smoking on hearing via conventional and ultra-high-frequency pure tone audiometry (PTA), and OAEs, specifically spontaneous OAEs, click-evoked OAEs, and distortion-product OAEs. Material/Methods The study included 84 healthy volunteers aged 25–45 years (mean 34), among them 46 women (25 non-smokers and 21 smokers) and 38 men (16 non-smokers and 22 smokers). The protocol of the study included otoscopic examination, tympanometry, low-, moderate-, and ultra-high-frequency PTA, evaluation of spontaneous click-evoked (CEAOEs) and distortion-product otoacoustic emissions (DPOAEs), assessment of the DP-grams for 2f1-f2 (f1 from 977 to5 164 Hz), and input/output function at L2 primary tone level of 40–70 dB SPL. Results Smokers and non-smokers did not differ significantly in terms of their hearing thresholds assessed with tone audiometry. Male smokers presented with significantly lower levels of CEAOEs and DPOAEs than both male non-smokers and female smokers. Conclusions Smoking does not modulate a hearing threshold determined with PTA at low, moderate, and ultra-high frequencies, but causes a significant decrease in OAE levels. This effect was observed only in males, which implies that they are more susceptible to smoking-induced hearing impairment. Sex-specific differences in otoacoustic emissions level may reflect influences of genetic, hormonal, behavioral, and/or environmental factors. PMID:28110343

  4. Persistence of Smoking-Induced Dysregulation of MiRNA Expression in the Small Airway Epithelium Despite Smoking Cessation

    PubMed Central

    Strulovici-Barel, Yael; Salit, Jacqueline; Staudt, Michelle R.; Ahmed, Joumana; Tilley, Ann E.; Yee-Levin, Jenny; Hollmann, Charleen; Harvey, Ben-Gary; Kaner, Robert J.; Mezey, Jason G.; Sridhar, Sriram; Pillai, Sreekumar G.; Hilton, Holly; Wolff, Gerhard; Bitter, Hans; Visvanathan, Sudha; Fine, Jay S.; Stevenson, Christopher S.; Crystal, Ronald G.

    2015-01-01

    Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD) and lung cancer remains significantly higher compared to healthy nonsmokers. Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE), we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 9 healthy nonsmokers and 10 healthy smokers, before and after they quit smoking for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy nonsmokers (p<0.01, fold-change >1.5), with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway being the top identified enriched pathway of the target genes of the persistent dysregulated miRNAs. In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammatory diseases or lung cancer, it is likely that persistent smoking-related changes in SAE miRNAs play a role in the subsequent development of these disorders. PMID:25886353

  5. Bhas 42 cell transformation activity of cigarette smoke condensate is modulated by selenium and arsenic.

    PubMed

    Han, Sung Gu; Pant, Kamala; Bruce, Shannon W; Gairola, C Gary

    2016-04-01

    Cigarette smoking remains a major health risk worldwide. Development of newer tobacco products requires the use of quantitative toxicological assays. Recently, v-Ha-ras transfected BALB/c3T3 (Bhas 42) cell transformation assay was established that simulates the two-stage animal tumorigenesis model and measures tumor initiating and promoting activities of chemicals. The present study was performed to assess the feasibility of using this Bhas 42 cell transformation assay to determine the initiation and promotion activities of cigarette smoke condensate (CSC) and its water soluble fraction. Further, the modulating effects of selenium and arsenic on cigarette smoke-induced cell transformation were investigated. Dimethyl sulfoxide (DMSO) and water extracts of CSC (CSC-D and CSC-W, respectively) were tested at concentrations of 2.5-40 µg mL(-1) in the initiation or promotion assay formats. Initiation protocol of the Bhas 42 assay showed a 3.5-fold increase in transformed foci at 40 µg mL(-1) of CSC-D but not CSC-W. The promotion phase of the assay yielded a robust dose response with CSC-D (2.5-40 µg mL(-1)) and CSC-W (20-40 µg mL(-1)). Preincubation of cells with selenium (100 nM) significantly reduced CSC-induced increase in cell transformation in initiation assay. Co-treatment of cells with a sub-toxic dose of arsenic significantly enhanced cell transformation activity of CSC-D in promotion assay. The results suggest a presence of both water soluble and insoluble tumor promoters in CSC, a role of oxidative stress in CSC-induced cell transformation, and usefulness of Bhas 42 cell transformation assay in comparing tobacco product toxicities and in studying the mechanisms of tobacco carcinogenesis.

  6. Effects of prenatal exposure to cigarette smoke on offspring tumor susceptibility and associated immune mechanisms.

    PubMed

    Ng, Sheung P; Silverstone, Allen E; Lai, Zhi-Wei; Zelikoff, Judith T

    2006-01-01

    Epidemiologic evidence suggests that prenatal exposure to intact (unfractionated) cigarette smoke (CS) increases the incidence of cancer in the offspring. A toxicology study was carried out to examine the effects and underlying mechanisms of prenatal exposure to mainstream cigarette smoke (MCS) on offspring resistance to tumor challenge and surveillance mechanisms critical for the recognition and destruction of tumors. Pregnant B6C3F1 mice were exposed by inhalation to MCS for 5 days/week (4 h/day from gestational day 4 to parturition). Smoke-induced effects on offspring-host resistance to transplanted tumor cells; natural killer (NK) cell and cytotoxic T-lymphocyte (CTL) activity; cytokine levels; lymphoid organ immune cell subpopulations; and histology-were examined in 5-, 10- and 20-week-old male and female offspring. At a concentration of smoke roughly equivalent to smoking <1 pack of cigarettes/day, prenatally exposed male offspring challenged at 5 week of age with EL4 lymphoma cells demonstrated a greater than two-fold increase in tumor incidence (relative to age-/gender-matched air-exposed offspring); tumors in prenatally smoke-exposed pups also grew significantly faster. Cytotoxic T-lymphocyte activity in the smoke-exposed 5- and 10-week-old male pups was significantly less than that of the age- and gender-matched controls. No effects of prenatal CS exposure were observed on offspring NK activity, cytokine levels, lymphoid organ histology, or immune cell subpopulations. Results demonstrated that exposure of pregnant mice to a relevant dose of MCS decreased offspring resistance against transplanted tumor cells and persistently reduced CTL activity in prenatally exposed pups. This study provides biological plausibility for the epidemiologic data indicating that children of mothers who smoke during pregnancy have a greater risk of developing cancer in later life.

  7. Sleep deprivation increases cigarette smoking.

    PubMed

    Hamidovic, Ajna; de Wit, Harriet

    2009-09-01

    Loss of sleep may impair the ability to abstain from drug use, through any of a number of mechanisms. Sleep loss may increase drug use by impairing attention and inhibitory control, increasing the value of drug rewards over other rewards, or by inducing mood states that facilitate use of a drug. In the present study, we examined whether sleep deprivation (SD) would increase smoking in cigarette smokers, and whether it would do so by impairing attention or inhibitory control. Healthy cigarette smokers (N=14) were tested in a two-session within subject study, after overnight SD or after a normal night's sleep. Subjects were tested in both conditions in randomized order, after abstaining from cigarettes for 48 hours. The procedure was designed to model the human relapse situation. On each 6-h laboratory session after sleep or no sleep, subjects completed mood and craving questionnaires, tasks measuring behavioral inhibition and attention, and a choice procedure in which they chose between money and smoking cigarettes. SD increased self-reported fatigue and decreased arousal, it increased the number of cigarettes subjects chose to smoke, impaired behavioral inhibition and attention. However, the impairments in inhibition or attention were not related to the increase in smoking. It is possible that SD increases smoking because smokers expect that it will reduce sleepiness. Thus, the findings suggest that sleep loss may increase the likelihood of smoking during abstinence not through inhibitory or attentional mechanisms but because of the potential of nicotine to reduce subjective sleepiness.

  8. 19 CFR 11.2a - Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers and tubes. 11.2a Section 11.2a Customs Duties U.S... cigars, cigarettes and cigarette papers and tubes. Cigars, cigarettes, and cigarette papers and tubes...

  9. 19 CFR 11.2a - Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers and tubes. 11.2a Section 11.2a Customs Duties U.S... cigars, cigarettes and cigarette papers and tubes. Cigars, cigarettes, and cigarette papers and tubes...

  10. 19 CFR 11.2a - Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers and tubes. 11.2a Section 11.2a Customs Duties U.S... cigars, cigarettes and cigarette papers and tubes. Cigars, cigarettes, and cigarette papers and tubes...

  11. 19 CFR 11.2a - Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers and tubes. 11.2a Section 11.2a Customs Duties U.S... cigars, cigarettes and cigarette papers and tubes. Cigars, cigarettes, and cigarette papers and tubes...

  12. 19 CFR 11.2a - Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers and tubes. 11.2a Section 11.2a Customs Duties U.S... cigars, cigarettes and cigarette papers and tubes. Cigars, cigarettes, and cigarette papers and tubes...

  13. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model

    PubMed Central

    Huang, Yun-Ching; Chin, Chih-Chien; Chen, Chih-Shou; Shindel, Alan. W.; Ho, Dong-Ru; Lin, Ching-Shwun; Shi, Chung-Sheng

    2015-01-01

    Cigarette use is an independent risk factor for the development of erectile dysfunction (ED). While the association between chronic smoking and ED is well established, the fundamental mechanism(s) of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS) for 4 weeks (n = 10), 12 weeks (n = 10), and 24 weeks (n = 10). At the 24-week time point all rats were assessed with intracavernous pressure (ICP) during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS). Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP) was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED. PMID:26491965

  14. Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells

    PubMed Central

    Syed, Nazia; Solanki, Hitendra S.; Puttamallesh, Vinuth N.; Balaji, Sai A.; Nanjappa, Vishalakshi; Datta, Keshava K.; Babu, Niraj; Renuse, Santosh; Patil, Arun H.; Izumchenko, Evgeny; Prasad, T.S. Keshava; Chang, Xiaofei; Rangarajan, Annapoorni; Sidransky, David; Pandey, Akhilesh; Gowda, Harsha; Chatterjee, Aditi

    2016-01-01

    Epidemiological data clearly establishes cigarette smoking as one of the major cause for lung cancer worldwide. Recently, targeted therapy has become one of the most preferred modes of treatment for cancer. Though certain targeted therapies such as anti-EGFR are in clinical practice, they have shown limited success in lung cancer patients who are smokers. This demands discovery of alternative drug targets through systematic investigation of cigarette smoke-induced signaling mechanisms. To study the signaling events activated in response to cigarette smoke, we carried out SILAC-based phosphoproteomic analysis of H358 lung cancer cells chronically exposed to cigarette smoke. We identified 1,812 phosphosites, of which 278 phosphosites were hyperphosphorylated (≥ 3-fold) in H358 cells chronically exposed to cigarette smoke. Our data revealed hyperphosphorylation of S560 within the conserved kinase domain of PAK6. Activation of PAK6 is associated with various processes in cancer including metastasis. Mechanistic studies revealed that inhibition of PAK6 led to reduction in cell proliferation, migration and invasion of the cigarette smoke treated cells. Further, siRNA mediated silencing of PAK6 resulted in decreased invasive abilities in a panel of non-small cell lung cancer (NSCLC) cells. Consistently, mice bearing tumor xenograft showed reduced tumor growth upon treatment with PF-3758309 (group II PAK inhibitor). Immunohistochemical analysis revealed overexpression of PAK6 in 66.6% (52/78) of NSCLC cases in tissue microarrays. Taken together, our study indicates that PAK6 is a promising novel therapeutic target for NSCLC, especially in smokers. PMID:27542207

  15. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model.

    PubMed

    Huang, Yun-Ching; Chin, Chih-Chien; Chen, Chih-Shou; Shindel, Alan W; Ho, Dong-Ru; Lin, Ching-Shwun; Shi, Chung-Sheng

    2015-01-01

    Cigarette use is an independent risk factor for the development of erectile dysfunction (ED). While the association between chronic smoking and ED is well established, the fundamental mechanism(s) of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS) for 4 weeks (n = 10), 12 weeks (n = 10), and 24 weeks (n = 10). At the 24-week time point all rats were assessed with intracavernous pressure (ICP) during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS). Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP) was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED.

  16. Electronic cigarettes and nicotine clinical pharmacology

    PubMed Central

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

  17. Aldehyde Detection in Electronic Cigarette Aerosols

    PubMed Central

    2017-01-01

    Acetaldehyde, acrolein, and formaldehyde are the principal toxic aldehydes present in cigarette smoke and contribute to the risk of cardiovascular disease and noncancerous pulmonary disease. The rapid growth of the use of electronic cigarettes (e-cigarettes) has raised concerns over emissions of these harmful aldehydes. This work determines emissions of these aldehydes in both free and bound (aldehyde–hemiacetal) forms and other carbonyls from the use of e-cigarettes. A novel silicon microreactor with a coating phase of 4-(2-aminooxyethyl)-morpholin-4-ium chloride (AMAH) was used to trap carbonyl compounds in the aerosols of e-cigarettes via oximation reactions. AMAH–aldehyde adducts were measured using gas chromatography–mass spectrometry. 1H nuclear magnetic resonance spectroscopy was used to analyze hemiacetals in the aerosols. These aldehydes were detected in the aerosols of all e-cigarettes. Newer-generation e-cigarette devices generated more aldehydes than the first-generation e-cigarettes because of higher battery power output. Formaldehyde–hemiacetal was detected in the aerosols generated from some e-liquids using the newer e-cigarette devices at a battery power output of 11.7 W and above. The emission of these aldehydes from all e-cigarettes, especially higher levels of aldehydes from the newer-generation e-cigarette devices, indicates the risk of using e-cigarettes. PMID:28393137

  18. Polonium-210 budget in cigarettes.

    PubMed

    Khater, Ashraf E M

    2004-01-01

    Due to the relatively high activity concentrations of (210)Po and (210)Pb that are found in tobacco and its products, cigarette smoking highly increases the internal intake of both radionuclides and their concentrations in the lung tissues. That might contribute significantly to an increase in the internal radiation dose and in the number of instances of lung cancer observed among smokers. Samples of most frequently smoked fine and popular brands of cigarettes were collected from those available on the Egyptian market. (210)Po activity concentrations were measured by alpha spectrometry, using surface barrier detectors, following the radiochemical separation of polonium. Samples of fresh tobacco, wrapping paper, fresh filters, ash and post-smoking filters were spiked with (208)Po for chemical recovery calculation. The samples were dissolved using mineral acids (HNO(3), HCl and HF). Polonium was spontaneously plated-out on stainless steel disks from diluted HCl solution. The (210)Po activity concentration in smoke was estimated on the basis of its activity in fresh tobacco and wrapping paper, fresh filter, ash and post-smoking filters. The percentages of (210)Po activity concentrations that were recovered from the cigarette tobacco to ash, post-smoking filters, and smokes were assessed. The results of this work indicate that the average (range) activity concentration of (210)Po in cigarette tobacco was 16.6 (9.7-22.5) mBq/cigarette. The average percentages of (210)Po content in fresh tobacco plus wrapping paper that were recovered by post-smoking filters, ash and smoke were 4.6, 20.7 and 74.7, respectively. Cigarette smokers, who are smoking one pack (20 cigarettes) per day, are inhaling on average 123 mBq/d of (210)Po and (210)Pb each. The annual effective doses were calculated on the basis of (210)Po and (210)Pb intake with the cigarette smoke. The mean values of the annual effective dose for smokers (one pack per day) were estimated to be 193 and 251 microSv from

  19. Benzene formation in electronic cigarettes

    PubMed Central

    Pankow, James F.; Kim, Kilsun; McWhirter, Kevin J.; Luo, Wentai; Escobedo, Jorge O.; Strongin, Robert M.; Duell, Anna K.; Peyton, David H.

    2017-01-01

    Background/Objective The heating of the fluids used in electronic cigarettes (“e-cigarettes”) used to create “vaping” aerosols is capable of causing a wide range of degradation reaction products. We investigated formation of benzene (an important human carcinogen) from e-cigarette fluids containing propylene glycol (PG), glycerol (GL), benzoic acid, the flavor chemical benzaldehyde, and nicotine. Methods/Main results Three e-cigarette devices were used: the JUULTM “pod” system (provides no user accessible settings other than flavor cartridge choice), and two refill tank systems that allowed a range of user accessible power settings. Benzene in the e-cigarette aerosols was determined by gas chromatography/mass spectrometry. Benzene formation was ND (not detected) in the JUUL system. In the two tank systems benzene was found to form from propylene glycol (PG) and glycerol (GL), and from the additives benzoic acid and benzaldehyde, especially at high power settings. With 50:50 PG+GL, for tank device 1 at 6W and 13W, the formed benzene concentrations were 1.9 and 750 μg/m3. For tank device 2, at 6W and 25W, the formed concentrations were ND and 1.8 μg/m3. With benzoic acid and benzaldehyde at ~10 mg/mL, for tank device 1, values at 13W were as high as 5000 μg/m3. For tank device 2 at 25W, all values were ≤~100 μg/m3. These values may be compared with what can be expected in a conventional (tobacco) cigarette, namely 200,000 μg/m3. Thus, the risks from benzene will be lower from e-cigarettes than from conventional cigarettes. However, ambient benzene air concentrations in the U.S. have typically been 1 μg/m3, so that benzene has been named the largest single known cancer-risk air toxic in the U.S. For non-smokers, chronically repeated exposure to benzene from e-cigarettes at levels such as 100 or higher μg/m3 will not be of negligible risk. PMID:28273096

  20. Cigarette smoke and lung cancer

    SciTech Connect

    Martonen, T.B.; Hofmann, W.; Lowe, J.E.

    1987-01-01

    Cigarette smoke has been implicated in a causal relationship with carcinoma of the lung. An intriguing feature of the disease is the site-selectivity with which bronchogenic cancer manifests itself; most cancers are detected in the main, lobar and segmental bronchi, perhaps specifically at airway bifurcations. The elevated risk of lung cancer to smokers may result from a complex interplay between smoking and exposure to ambient Rn progeny, including the promotional-effect role (as opposed to being the initiating event) of cigarette smoke in tumor development. It has been determined that smokers exposed to average indoor Rn progency levels receive surprisingly high doses at hot spots within bronchial bifurcations.

  1. Are all cigarettes just the same? Female's perceptions of slim, coloured, aromatized and capsule cigarettes.

    PubMed

    Moodie, Crawford; Ford, Allison; Mackintosh, Anne; Purves, Richard

    2015-02-01

    Twelve focus groups in Glasgow (Scotland) were conducted with female non-smokers and occasional smokers aged 12-24 years (N = 75), with each group shown 11 cigarettes: two (standard) cigarettes with cork filters; two coloured cigarettes (pink or brown); four slim cigarettes; an aromatized black cigarette; a menthol cigarette and a cigarette with a flavour-changing rupturable capsule in the filter. Participants were asked to rank the cigarettes by appeal, taste and harm. The capsule cigarette was then discussed in depth. The pink coloured cigarette and slim cigarettes created significant interest and were generally perceived as most appealing and pleasant tasting, and least harmful. The black aromatized cigarette received a mixed response, with some disliking the dark colour and associating it with low appeal, strong taste and increased harm, whereas for others the smell helped to enhance appeal and taste perceptions and lower perceptions of harm. The novel capsule cigarette, when discussed in-depth, was viewed very positively. Just as research shows that cigarette packs can influence perceptions of appeal, harm and taste, this study suggests that the actual cigarettes can do likewise. The findings have implications for tobacco education and policy.

  2. Prenatal cigarette smoke exposure effects on apoptotic and nicotinic acetylcholine receptor expression in the infant mouse brainstem.

    PubMed

    Vivekanandarajah, Arunnjah; Chan, Yik Lung; Chen, Hui; Machaalani, Rita

    2016-03-01

    Infants exposed to cigarette smoked during pregnancy into infancy have increased respiratory and cardiac abnormalities. Nicotine, the major neurotoxic component of cigarette smoke, induces its actions by binding to nicotinic acetylcholine receptors (nAChR), with one downstream effect being increased apoptosis. Using a pre- into post- natal cigarette smoke exposure mouse model (SE), we studied the immunohistochemical expression of nAChR subunits α2, α3, α4, α5, α7, α9, β1 and β2 and two markers of apoptosis, active caspase-3 and TUNEL, in seven nuclei of the medulla and facial nucleus of the pons in male mice. Pups of dams exposed to two cigarettes (nicotine ≤1.2mg, CO ≤15mg) twice daily for six weeks prior to mating, during gestation and lactation (n=5; SE), were compared to pups exposed to air under the same condition (n=5; SHAM) at P20. Results showed that the hypoglossal nucleus had increased α3, α4, α7, α9, Casp-3 and TUNEL, dorsal motor nucleus of the vagus had increased α3, α5, α7, β1 and Casp-3, nucleus of the solitary tract had increased α3 but decreased α4, α5, β1 and apoptosis, cuneate nucleus had increased α3, β2 and Casp- 3, but decreased α5, nucleus of the spinal trigeminal tract had increased α3, α7, β1, lateral reticular nucleus had decreased β1, inferior olivary nucleus had increased β1 but decreased apoptosis, and the facial had increased α2, α3 and α7. This is the first study to demonstrate that nAChR subunits are affected following pre- into post-natal SE and that they simultaneously coincided with changes in apoptotic expression.

  3. E-cigarettes: promise or peril?

    PubMed

    Riker, Carol A; Lee, Kiyoung; Darville, Audrey; Hahn, Ellen J

    2012-03-01

    Electronic cigarettes (e-cigarettes) use a heating element to vaporize nicotine and other ingredients, simulating the visual, sensory, and behavioral aspects of smoking without the combustion of tobacco. An ever-growing number of companies around the world manufacture a wide variety of e-cigarette brands, despite scant information on the safety of the ingredients for human inhalation. This article provides an overview of the history, production, and marketing of e-cigarettes, the contents of e-cigarettes and vapor, how they are used, public health concerns, and implications for nursing practice, research, and policy development.

  4. Carbonyl compounds generated from electronic cigarettes.

    PubMed

    Bekki, Kanae; Uchiyama, Shigehisa; Ohta, Kazushi; Inaba, Yohei; Nakagome, Hideki; Kunugita, Naoki

    2014-10-28

    Electronic cigarettes (e-cigarettes) are advertised as being safer than tobacco cigarettes products as the chemical compounds inhaled from e-cigarettes are believed to be fewer and less toxic than those from tobacco cigarettes. Therefore, continuous careful monitoring and risk management of e-cigarettes should be implemented, with the aim of protecting and promoting public health worldwide. Moreover, basic scientific data are required for the regulation of e-cigarette. To date, there have been reports of many hazardous chemical compounds generated from e-cigarettes, particularly carbonyl compounds such as formaldehyde, acetaldehyde, acrolein, and glyoxal, which are often found in e-cigarette aerosols. These carbonyl compounds are incidentally generated by the oxidation of e-liquid (liquid in e-cigarette; glycerol and glycols) when the liquid comes in contact with the heated nichrome wire. The compositions and concentrations of these compounds vary depending on the type of e-liquid and the battery voltage. In some cases, extremely high concentrations of these carbonyl compounds are generated, and may contribute to various health effects. Suppliers, risk management organizations, and users of e-cigarettes should be aware of this phenomenon.

  5. Carbonyl Compounds Generated from Electronic Cigarettes

    PubMed Central

    Bekki, Kanae; Uchiyama, Shigehisa; Ohta, Kazushi; Inaba, Yohei; Nakagome, Hideki; Kunugita, Naoki

    2014-01-01

    Electronic cigarettes (e-cigarettes) are advertised as being safer than tobacco cigarettes products as the chemical compounds inhaled from e-cigarettes are believed to be fewer and less toxic than those from tobacco cigarettes. Therefore, continuous careful monitoring and risk management of e-cigarettes should be implemented, with the aim of protecting and promoting public health worldwide. Moreover, basic scientific data are required for the regulation of e-cigarette. To date, there have been reports of many hazardous chemical compounds generated from e-cigarettes, particularly carbonyl compounds such as formaldehyde, acetaldehyde, acrolein, and glyoxal, which are often found in e-cigarette aerosols. These carbonyl compounds are incidentally generated by the oxidation of e-liquid (liquid in e-cigarette; glycerol and glycols) when the liquid comes in contact with the heated nichrome wire. The compositions and concentrations of these compounds vary depending on the type of e-liquid and the battery voltage. In some cases, extremely high concentrations of these carbonyl compounds are generated, and may contribute to various health effects. Suppliers, risk management organizations, and users of e-cigarettes should be aware of this phenomenon. PMID:25353061

  6. Non-cigarette tobacco and the lung.

    PubMed

    Schivo, Michael; Avdalovic, Mark V; Murin, Susan

    2014-02-01

    Cigarette smoking is known to cause a wide range of damaging health outcomes; however, the effects of non-cigarette tobacco products are either unknown or perceived as less harmful than cigarettes. Smokeless tobacco, cigar smoking, and waterpipe smoking have increased in usage over the past few decades. Some experts believe that their use is reaching epidemic proportions. Factors such as a perception of harm reduction, targeted advertising, and unrecognized addiction may drive the increased consumption of non-cigarette tobacco products. In particular, the need for social acceptance, enjoyment of communal smoking activities, and exotic nature of waterpipe smoking fuels, in part, its popularity. The public is looking for "safer" alternatives to smoking cigarettes, and some groups advertise products such as smokeless tobacco and electronic cigarettes as the alternatives they seek. Though it is clear that cigar and waterpipe tobacco smoking are probably as dangerous to health as cigarette smoking, there is an opinion among users that the health risks are less compared to cigarette smoking. This is particularly true in younger age groups. In the cases of smokeless tobacco and electronic cigarettes, the risks to health are less clear and there may be evidence of a harm reduction compared to cigarettes. In this article, we discuss commonly used forms of non-cigarette tobacco products, their impacts on lung health, and relevant controversies surrounding their use.

  7. [The challenge of electronic cigarettes].

    PubMed

    Córdoba García, Rodrigo

    2014-01-01

    The electronic cigarette (e-cig) is a device with a conventional cigarette shape that releases a determined dose of nicotine vapour through an electronic heating process. The nicotine cartridges vary significantly in the amount of nicotine released, even within the same brand. Not all brands admit that they contain nicotine, but this is detected in the majority of units analysed. The e-cig usually contains a propellant, such as propylene glycol, which is a lung irritant. The short-term respiratory effect of the vapour of an e-cig is similar to that caused by the smoke of a cigarette, and is a cause of broncho-restriction. The majority of brands contain glycerine and at least one case of lipoid pneumonia has been detected due to this substance. Many brands contain traces of N-nitrosamines, heavy metals, and other products that are found in conventional cigarette smoke, but in a much higher proportion. There is currently no scientific evidence available that shows it is an effective device for quitting smoking, thus it should not be pro-actively recommended for this purpose, and may interfere with the use of demonstrated scientific evidence-based treatments for quitting smoking. It may have an undesirable effect on promoting the starting of smoking in adolescents or keeping adult smokers consuming nicotine and on gestural dependency. The toxicity of the vapour is not well known, but it is known that they are not innocuous, thus they should not be used in closed public spaces.

  8. The electronic cigarette: the new cigarette of the 21st century?*

    PubMed Central

    Knorst, Marli Maria; Benedetto, Igor Gorski; Hoffmeister, Mariana Costa; Gazzana, Marcelo Basso

    2014-01-01

    The electronic nicotine delivery system, also known as the electronic cigarette, is generating considerable controversy, not only in the general population but also among health professionals. Smokers the world over have been increasingly using electronic cigarettes as an aid to smoking cessation and as a substitute for conventional cigarettes. There are few available data regarding the safety of electronic cigarettes. There is as yet no evidence that electronic cigarettes are effective in treating nicotine addiction. Some smokers have reported using electronic cigarettes for over a year, often combined with conventional cigarettes, thus prolonging nicotine addiction. In addition, the increasing use of electronic cigarettes by adolescents is a cause for concern. The objective of this study was to describe electronic cigarettes and their components, as well as to review the literature regarding their safety; their impact on smoking initiation and smoking cessation; and regulatory issues related to their use. PMID:25410845

  9. The Impact of Trying Electronic Cigarettes on Cigarette Smoking by College Students: A Prospective Analysis

    PubMed Central

    Reboussin, Beth A; Debinski, Beata; Wagoner, Kimberly G.; Spangler, John; Wolfson, Mark

    2015-01-01

    Objectives. We assessed the impact of trying electronic cigarettes (e-cigarettes) on future cigarette smoking in a sample of smokers enrolled in college. Methods. In this longitudinal study, first-semester college students at 7 colleges in North Carolina and 4 in Virginia completed a baseline survey and 5 follow-up surveys between fall 2010 and fall 2013. Current cigarette smoking at wave 6 was the primary outcome. Participants (n = 271) reported current cigarette smoking at baseline and no history of e-cigarette use. We measured trying e-cigarettes at each wave, defined as use in the past 6 months. Results. By wave 5, 43.5% had tried e-cigarettes. Even after controlling for other variables associated with cigarette smoking, trying e-cigarettes was a significant predictor of cigarette smoking at wave 6 (adjusted odds ratio [AOR] = 2.48; 95% confidence interval [CI] = 1.32, 4.66), as were friends’ cigarette smoking (AOR = 4.20; 95% CI = 2.22, 7.96) and lifetime use of other tobacco products (AOR = 1.63; 95% CI = 1.22, 2.17). Conclusions. Trying e-cigarettes during college did not deter cigarette smoking and may have contributed to continued smoking. PMID:26066954

  10. The lung inflammation and skeletal muscle wasting induced by subchronic cigarette smoke exposure are not altered by a high-fat diet in mice.

    PubMed

    Hansen, Michelle J; Chen, Hui; Jones, Jessica E; Langenbach, Shenna Y; Vlahos, Ross; Gualano, Rosa C; Morris, Margaret J; Anderson, Gary P

    2013-01-01

    Obesity and cigarette smoking independently constitute major preventable causes of morbidity and mortality and obesity is known to worsen lung inflammation in asthma. Paradoxically, higher body mass index (BMI) is associated with reduced mortality in smoking induced COPD whereas low BMI increases mortality risk. To date, no study has investigated the effect of a dietary-induced obesity and cigarette smoke exposure on the lung inflammation and loss of skeletal muscle mass in mice. Male BALB/c mice were exposed to 4 cigarettes/day, 6 days/week for 7 weeks, or sham handled. Mice consumed either standard laboratory chow (3.5 kcal/g, 12% fat) or a high fat diet (HFD, 4.3 kcal/g, 32% fat). Mice exposed to cigarette smoke for 7 weeks had significantly more inflammatory cells in the BALF (P<0.05) and the mRNA expression of pro-inflammatory cytokines and chemokines was significantly increased (P<0.05); HFD had no effect on these parameters. Sham- and smoke-exposed mice consuming the HFD were significantly heavier than chow fed animals (12 and 13%, respectively; P<0.05). Conversely, chow and HFD fed mice exposed to cigarette smoke weighed 16 and 15% less, respectively, compared to sham animals (P<0.05). The skeletal muscles (soleus, tibialis anterior and gastrocnemius) of cigarette smoke-exposed mice weighed significantly less than sham-exposed mice (P<0.05) and the HFD had no protective effect. For the first time we report that cigarette smoke exposure significantly decreased insulin-like growth factor-1 (IGF-1) mRNA expression in the gastrocnemius and tibialis anterior and IGF-1 protein in the gastrocnemius (P<0.05). We have also shown that cigarette smoke exposure reduced circulating IGF-1 levels. IL-6 mRNA expression was significantly elevated in all three skeletal muscles of chow fed smoke-exposed mice (P<0.05). In conclusion, these findings suggest that a down-regulation in local IGF-1 may be responsible for the loss of skeletal muscle mass following cigarette smoke

  11. ILLICIT CIGARETTE TRADE IN THAILAND

    PubMed Central

    Pavananunt, Pirudee

    2012-01-01

    The sale and consumption of illicit tobacco increases consumption, impacts public health, reduces tax revenue and provides an argument against tax increases. Thailand has some of the best tobacco control policies in Southeast Asia with one of the highest tobacco tax rates, but illicit trade has the potential to undermine these policies and needs investigating. Two approaches were used to assess illicit trade between 1991 and 2006: method 1, comparison of tobacco used based on tobacco taxes paid and survey data, and method 2, discrepancies between export data from countries exporting tobacco to Thailand and Thai official data regarding imports. A three year average was used to smooth differences due to lags between exports and imports. For 1991–2006, the estimated manufactured cigarette consumption from survey data was considerably lower than sales tax paid, so method 1 did not provide evidence of cigarette tax avoidance. Using method 2 the trade difference between reported imports and exports, indicates 10% of cigarettes consumed in Thailand (242 million packs per year) between 2004 and 2006 were illicit. The loss of revenue amounted to 4,508 million Baht (2002 prices) in the same year, that was 14% of the total cigarette tax revenue. Cigarette excise tax rates had a negative relationship with consumption trends but no relation with the level of illicit trade. There is a need for improved policies against smuggling to combat the rise in illicit tobacco consumption. Regional coordination and implementation of protocols on illicit trade would help reduce incentives for illegal tax avoidance. PMID:22299425

  12. Smoking-induced affect modulation in nonwithdrawn smokers with posttraumatic stress disorder, depression, and in those with no psychiatric disorder.

    PubMed

    Cook, Jessica W; Baker, Timothy B; Beckham, Jean C; McFall, Miles

    2017-02-01

    This research sought to determine whether smoking influences affect by means other than withdrawal reduction. Little previous evidence suggests such an effect. We surmised that such an effect would be especially apparent in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), 2 disorders that are frequently comorbid with smoking and that involve dysregulated affect. Participants were U.S. veterans who were regular smokers (N = 159): 52 with PTSD (58% with comorbid MDD), 51 with MDD, and 56 controls with no psychiatric disorder. During 3 positive and 3 negative mood induction trials (scheduled over 2 sessions), nonwithdrawn participants smoked either a nicotine-containing cigarette (NIC+), a nicotine-free cigarette (NIC-), or held a pen. Positive and negative affect were each measured before and after mood induction. Results showed a significant 2-way interaction of Smoking Condition × Time on negative affect during the negative mood induction (F(6, 576) = 2.41, p = .03) in those with PTSD and controls. In these groups, both NIC+ and NIC-, relative to pen, produced lower negative affect ratings after the negative mood induction. There was also a 2-way interaction of Smoking Condition × Time on positive affect response to the positive mood induction among those with PTSD and controls (F(6, 564) = 3.17, p = .005) and among MDD and controls (F(6, 564) = 2.27, p = .036). Among all smokers, NIC+ enhanced the magnitude and duration of positive affect more than did NIC-. Results revealed affect modulation outside the context of withdrawal relief; such effects may motivate smoking among those with psychiatric diagnoses, and among smokers in general. (PsycINFO Database Record

  13. Hand rolling cigarette papers as the reference point for regulating cigarette fire safety

    PubMed Central

    Laugesen, M; Duncanson, M; Fraser, T; McClellan, V; Linehan, B; Shirley, R

    2003-01-01

    Aim: To compare the burning characteristics of the tobacco and paper of manufactured and hand rolled cigarettes, and set a fire safety standard of manufacture to largely reduce the fire risk from discarded cigarettes. Methods: (1) Cigarette extinction test of ignition strength: 40 cigarettes per brand, lit and placed on 15 layers of filter paper, in accordance with ASTM test standard E2187-02. (2) Citrate extracted by 0.1N hydrochloric acid from cigarette papers and from tobacco in manufactured cigarettes, the supernatant analysed by high performance liquid chromatography using ultraviolet visual light spectrophotometer. (3) Survey of 750 nationally representative adults age 18 years and over, by telephone, including 184 smokers. Materials: (a) New Zealand made Holiday, and Horizon, and US made Marlboro manufactured cigarettes; (b) US manufactured Merit with banded paper; (c) Holiday, Horizon and Marlboro hand rolling tobaccos, hand rolled in Rizla cigarette papers; (d) manufactured cigarettes as in (a), reconstructed using Rizla hand rolling cigarette papers. Results: 1. (a) For each brand of manufactured cigarettes, 40/40 burnt full length; (b) for Merit banded paper cigarettes 29/40 (73%) burnt full length; (c) for each brand of hand rolled cigarettes 0/40 burnt full length; (d) 0/40 manufactured cigarettes reconstructed with Rizla hand rolling paper burnt full length. 2. Citrate content: (a) In manufactured cigarette papers: 0.3–0.8 mg; in tobacco of manufactured cigarettes: Holiday 0, Horizon 0, Marlboro 8.8 mg; (b) Merit: in banded paper 0.418 mg; in tobacco 10.23 mg; (c) In hand rolled cigarettes: in the papers < 0.08 mg; in hand rolled tobacco 13.3–15.0 mg; (d) In hand rolling papers of reconstructed cigarettes: < 0.018 mg. 3. Requiring manufactured cigarettes to compulsorily self-extinguish when left unattended was supported by 67% of smokers, 61% of manufactured cigarette smokers, 82% of hand rolled smokers, and by 68% of non-smokers. Conclusion: The

  14. E-cigarettes: facts, perceptions, and marketing messages.

    PubMed

    Carr, Ellen R

    2014-02-01

    Electronic cigarettes (e-cigarettes) are perceived as an alternative to standard tobacco cigarette smoking, primarily because of the e-cigarette industry's marketing messages. However, scientific studies about e-cigarette safety and efficacy remain limited. This column presents some of the issues associated with e-cigarette use, such as potential components of regulation, perceptions that e-cigarettes can help users quit smoking, and free-wheeling marketing strategies that include expanding e-cigarette use to young people. Nurses can be a reliable source of information about e-cigarettes.

  15. Influence of cigarette smoking on human autonomic function

    NASA Technical Reports Server (NTRS)

    Niedermaier, O. N.; Smith, M. L.; Beightol, L. A.; Zukowska-Grojec, Z.; Goldstein, D. S.; Eckberg, D. L.

    1993-01-01

    BACKGROUND. Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. METHODS AND RESULTS. We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. CONCLUSIONS. In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.

  16. 21 CFR 1141.14 - Misbranding of cigarettes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Misbranding of cigarettes. 1141.14 Section 1141.14...) TOBACCO PRODUCTS CIGARETTE PACKAGE AND ADVERTISING WARNINGS; (Eff. 9-22-12) Cigarette Package and Advertising Warnings § 1141.14 Misbranding of cigarettes. (a) A cigarette shall be deemed to be...

  17. Association Between Electronic Cigarette Use and Openness to Cigarette Smoking Among US Young Adults

    PubMed Central

    Apelberg, Benjamin J.; Ambrose, Bridget K.; Green, Kerry M.; Choiniere, Conrad J.; Bunnell, Rebecca; King, Brian A.

    2015-01-01

    Introduction: Use of electronic nicotine delivery systems (ENDS), including electronic cigarettes (e-cigarettes), is increasing. One concern is the appeal of these products to youth and young adults and the potential to influence perceptions and use of conventional cigarettes. Methods: Using data from the 2012–2013 National Adult Tobacco Survey, characteristics of adults aged 18–29 years who had never established cigarette smoking behavior were examined by ever use of e-cigarettes, demographics, and ever use of other tobacco products (smokeless tobacco, cigars, hookah, and cigarettes). Multivariate logistic regression was used to examine the relationship between e-cigarette use and openness to cigarette smoking among young adults, defined as the lack of a firm intention not to smoke soon or in the next year. Results: Among young adults who had never established cigarette smoking behavior (unweighted n = 4,310), 7.9% reported having ever tried e-cigarettes, and 14.6% of those who reported having ever tried e-cigarettes also reported current use of the product. Ever e-cigarette use was associated with being open to cigarette smoking (adjusted odds ratio = 2.4; 95% confidence interval = 1.7, 3.3), as was being male, aged 18–24 years, less educated, and having ever used hookah or experimented with conventional cigarettes. Conclusions: Ever use of e-cigarettes and other tobacco products was associated with being open to cigarette smoking. This study does not allow us to assess the directionality of this association, so future longitudinal research is needed to illuminate tobacco use behaviors over time as well as provide additional insight on the relationship between ENDS use and conventional cigarette use among young adult populations. PMID:25378683

  18. Effects of cigarette smoke extracts on the progression and metastasis of human ovarian cancer cells via regulating epithelial-mesenchymal transition.

    PubMed

    Jeon, So-Ye; Go, Ryeo-Eun; Heo, Jae-Rim; Kim, Cho-Won; Hwang, Kyung-A; Choi, Kyung-Chul

    2016-10-01

    Cigarette smoke (CS) contains over 60 well-established carcinogens, and there are strong links between these carcinogens and smoking-induced cancers. In this study we investigated whether three types of cigarette smoke extracts (CSEs), 3R4F (standard cigarette), CSE1 and CSE2 (two commercial cigarettes), affect the proliferation, migration, and invasive activity of BG-1 human ovarian cancer cells. All three types of CSEs increased BG-1 cell proliferation at nicotine concentrations of 1.5μM-2.1μM in a cell viability assay. The protein expressions of cyclin D1 and cyclin E1 were increased, while p21 and p27 expression was decreased by Western blot assay. However, they did not show a consistent dose-dependent tendency. The protein expressions of Bax and p53, pro-apoptotic genes, were also decreased by CSEs. The expression of E-cadherin, an epithelial marker, was reduced in the treatment of CSEs while the expression of its reverse transition marker, N-cadherin, was slightly increased by CSEs containing 2.1μM of nicotine, but a statistical significance was not observed. Epithelial-mesenchymal transition (EMT)-associated transcriptional factors, Snail and Slug, were also up-regulated by treatment with CSEs, indicating that CSEs can increase the EMT process in BG-1 ovarian cancer cells. In addition, CSEs increased the migratory and invasive propensity of cancer cells. These functional alterations were associated with changes in metastasis-related gene expression. Upon exposure to CSEs, the expression of MMP-9 and cathepsin D was increased. Taken together, we confirmed that CSEs increased the growth, migration, and invasion of human ovarian cancer cells by regulating cell cycle, apoptosis, EMT, and metastasis related cellular markers and signaling proteins. Based on the results, cigarette smokers of women might be at a higher risk of ovarian cancer than non-smokers.

  19. E-Cigarette Use among Smokers with Serious Mental Illness

    PubMed Central

    Prochaska, Judith J.; Grana, Rachel A.

    2014-01-01

    Background We examined electronic cigarette (EC) use, correlates of use, and associated changes in smoking behavior among smokers with serious mental illness in a clinical trial. Methods Adult smokers were recruited during acute psychiatric hospitalization (N = 956, 73% enrollment among approached smokers) in the San Francisco Bay Area between 2009–2013. At baseline, participants averaged 17 (SD = 10) cigarettes per day for 19 (SD = 14) years; 24% intended to quit smoking in the next month. Analyses examined frequency and correlates of EC use reported over the 18-month trial and changes in smoking behavior by EC use status. Findings EC use was 11% overall, and by year of enrollment, increased from 0% in 2009 to 25% in 2013. In multiple logistic regression, the likelihood of EC use was significantly greater with each additional year of recruitment, for those aged 18–26, and for those in the preparation versus precontemplation stage of change, and unlikely among Hispanic participants. EC use was unrelated to gender, psychiatric diagnosis, and measures of tobacco dependence at baseline. Further, over the 18-month trial, EC use was not associated with changes in smoking status or, among continued smokers, with reductions in cigarettes per day. Interpretation Within a clinical trial with smokers with serious mental illness, EC use increased over time, particularly among younger adults and those intending to quit tobacco. EC use was unrelated to changes in smoking. The findings are of clinical interest and warrant further study. PMID:25419703

  20. 19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S...; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and cigarette papers and tubes apply in accordance with the regulations of the Bureau of Alcohol, Tobacco,...

  1. 19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S...; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and cigarette papers and tubes apply in accordance with the regulations of the Bureau of Alcohol, Tobacco,...

  2. 19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S...; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and cigarette papers and tubes apply in accordance with the regulations of the Bureau of Alcohol, Tobacco,...

  3. 19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S...; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and cigarette papers and tubes apply in accordance with the regulations of the Bureau of Alcohol, Tobacco,...

  4. 19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S...; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and cigarette papers and tubes apply in accordance with the regulations of the Bureau of Alcohol, Tobacco,...

  5. Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress

    SciTech Connect

    Cheng, Ya-Hsin; Huang, Su-Chin; Lin, Chun-Ju; Cheng, Li-Chuan; Li, Lih-Ann

    2012-03-15

    Environmental cigarette smoke has been suggested to promote lung adenocarcinoma progression through aryl hydrocarbon receptor (AhR)-signaled metabolism. However, whether AhR facilitates metabolic activation or detoxification in exposed adenocarcinoma cells remains ambiguous. To address this question, we have modified the expression level of AhR in two human lung adenocarcinoma cell lines and examined their response to an extract of cigarette sidestream smoke particulates (CSSP). We found that overexpression of AhR in the CL1-5 cell line reduced CSSP-induced ROS production and oxidative DNA damage, whereas knockdown of AhR expression increased ROS level in CSSP-exposed H1355 cells. Oxidative stress sensor Nrf2 and its target gene NQO1 were insensitive to AhR expression level and CSSP treatment in human lung adenocarcinoma cells. In contrast, induction of AhR expression concurrently increased mRNA expression of xenobiotic-metabolizing genes CYP1B1, UGT1A8, and UGT1A10 in a ligand-independent manner. It appeared that AhR accelerated xenobiotic clearing and diminished associated oxidative stress by coordinate regulation of a set of phase I and II metabolizing genes. However, the AhR-signaled protection could not shield cells from constant oxidative stress. Prolonged exposure to high concentrations of CSSP induced G0/G1 cell cycle arrest via the p53–p21–Rb1 signaling pathway. Despite no effect on DNA repair rate, AhR facilitated the recovery of cells from growth arrest when CSSP exposure ended. AhR-overexpressing lung adenocarcinoma cells exhibited an increased anchorage-dependent and independent proliferation when recovery from exposure. In summary, our data demonstrated that AhR protected lung adenocarcinoma cells against CSSP-induced oxidative stress and promoted post-exposure clonogenicity. -- Highlights: ► AhR expression level influences cigarette sidestream smoke-induced ROS production. ► AhR reduces oxidative stress by coordinate regulation of

  6. [Electronic cigarette--a safe substitute for tobacco cigarette or a new threat?].

    PubMed

    Kośmider, Leon; Knysak, Jakub; Goniewicz, Maciej Łukasz; Sobczak, Andrzej

    2012-01-01

    The aim of this paper was to summarize up-to-date data on the new emerging nicotine containing product 'electronic cigarette', commonly referred as e-cigarette. We presented data on prevalence and popularity of various brands and models on domestic markets. Development of the new products with technical and chemical modifications was also described. We reviewed studies on chemical composition and efficacy of nicotine delivery from e-cigarettes and discussed its potential use as nicotine replacement for tobacco cigarettes. Regulatory policies on e-cigarette sale as nicotine containing product were also discussed. We concluded that e-cigarette might be an effective harm reduction tool but little is known about its safety, especially when used for a long time. Despite many positive findings from surveys among e-cigarettes users, there is need for comprehensive state-of-the-at clinical trials to show efficacy of e-cigarette as smoking cessation tool.

  7. Are E-cigarettes a safe and good alternative to cigarette smoking?

    PubMed

    Rom, Oren; Pecorelli, Alessandra; Valacchi, Giuseppe; Reznick, Abraham Z

    2015-03-01

    Electronic cigarettes (E-cigarettes) are devices that can vaporize a nicotine solution combined with liquid flavors instead of burning tobacco leaves. Since their emergence in 2004, E-cigarettes have become widely available, and their use has increased exponentially worldwide. E-cigarettes are aggressively advertised as a smoking cessation aid; as healthier, cheaper, and more socially acceptable than conventional cigarettes. In recent years, these claims have been evaluated in numerous studies. This review explores the development of the current E-cigarette and its market, prevalence of awareness, and use. The review also explores the beneficial and adverse effects of E-cigarettes in various aspects in accordance with recent research. The discussed aspects include smoking cessation or reduction and the health risks, social impact, and environmental consequences of E-cigarettes.

  8. Thermal injury patterns associated with electronic cigarettes

    PubMed Central

    Jiwani, Alisha Z; Williams, James F; Rizzo, Julie A; Chung, Kevin K; King, Booker T; Cancio, Leopoldo C

    2017-01-01

    E-cigarettes are typically lithium-ion battery-operated devices that simulate smoking by heating a nicotine-solution into a vapor that the user inhales. E-cigarette use is becoming rapidly popular as an alternative to traditional cigarette smoking. This report describes an emerging problem associated with e-cigarettes, consisting of 10 thermally injured patients seen at a single burn center over a 2-year period from 2014 to 2016. Our cohort was comprised mainly of young adults who sustained mixed partial and full thickness burns as a result of e-cigarette-related explosions. In many documented scenarios, a malfunctioning or over-heated battery is the cause. Our data support the need for increased awareness among healthcare providers and the general public of the potential harms of e-cigarette use, modification, storage, and charging. PMID:28123861

  9. Progress towards a fire-safe cigarette.

    PubMed

    Brigham, P A; McGuire, A

    1995-01-01

    About 1,000 deaths, 3,000 serious injuries, and several billion dollars in costs of property loss, health care and pain and suffering, result each year in the U.S. from fires started by dropped cigarettes. Efforts to prevent these losses have progressed from admonitory slogans to product-flammability standards to addressing the cigarette itself. Two recent federal studies have: a) concluded that it is technically feasible to produce a cigarette with a reduced likelihood of starting fires, and b) published a broadly validated method by which cigarette brands can be tested for this propensity. The long-term effort of scientists, legislators and public health activists to develop and implement a fire-safe cigarette standard also constitutes a legal liability challenge and a threat to the relative and absolute size of the cigarette market shares held by major U.S. tobacco companies.

  10. [E-Cigarettes – Friend or Foe?].

    PubMed

    Russi, Erich W

    2015-07-01

    Not nicotine, but an abundant amount of toxic chemicals produced by the combustion of tobacco are the cause of well-known health problems. E-cigarette vapor contains no or only minimal quantities of potentially harmful substances. Hence it can be assumed that vaping in adults is much less harmful than smoking of cigarettes. Furthermore, no data exist that e-cigarettes will encourage youngsters to become cigarette smokers. E-cigarette vaping has the potential to reduce the daily number of cigarettes smoked or facilitates cessation of smoking in heavily nicotine-dependent smokers, who keep on smoking despite a structured smoking cessation program. Health professionals should be aware of this type of nicotine substitution, since the controversial discussion is often emotional and not evidence-based.

  11. Parental Use of Electronic Cigarettes

    PubMed Central

    Garbutt, Jane M.; Miller, Whitney; Dodd, Sherry; Bobenhouse, Neil; Sterkel, Randall; Strunk, Robert C.

    2015-01-01

    Objective To describe parental use of electronic cigarettes (e-cigs) to better understand the safety risks posed to children. Methods Between June 24 and November 6, 2014, parents completed a self-administered paper survey during an office visit to 15 pediatric practices in a Mid-western practice based research network. Attitudes towards and use of e-cigs are reported for those aware of e-cigs before the survey. Results Ninety-five percent (628/658) of respondents were aware of e-cigs. Of these, 21.0% (130/622) had tried e-cigs at least once and 12.3% (77) reported e-cig use by ≥ 1 person in their household (4.0% exclusive e-cig use, 8.3% dual use with regular cigarettes). An additional 17.3% (109) reported regular cigarette use. Most respondents from e-cig using homes did not think e-cigs were addictive (36.9% minimally/not addictive, 25.0% did not know). While 73.7% believed that e-liquid was very dangerous for children if they ingested it, only 31.2% believed skin contact to be very dangerous. In 36.1% of e-cig using homes, neither childproof caps nor locks were used to prevent children's access to e-liquid. Only 15.3% reported their child's pediatrician was aware of e-cig use in the home. Conclusions E-cig use occurred in 1 in 8 homes, often concurrently with regular cigarettes. Many parents who used e-cigs were unaware of the potential health and safety hazards, including nicotine poisoning for children, and many did not store e-liquid safely. Pediatricians could provide education about e-cig associated safety hazards, but are unaware of e-cig use in their patient's homes. PMID:26306662

  12. Cigarette price minimization strategies used by adults.

    PubMed

    Pesko, Michael F; Kruger, Judy; Hyland, Andrew

    2012-09-01

    We used multivariate logistic regressions to analyze data from the 2006 to 2007 Tobacco Use Supplement of the Current Population Survey, a nationally representative sample of adults. We explored use of cigarette price minimization strategies, such as purchasing cartons of cigarettes, purchasing in states with lower after-tax cigarette prices, and purchasing on the Internet. Racial/ethnic minorities and persons with low socioeconomic status used these strategies less frequently at last purchase than did White and high-socioeconomic-status respondents.

  13. An Analysis of Electronic Cigarette and Cigarette Advertising in US Women's Magazines

    PubMed Central

    Basch, Corey Hannah; Mongiovi, Jennifer; Hillyer, Grace Clarke; Ethan, Danna; Hammond, Rodney

    2016-01-01

    Background: Traditional cigarette advertising has existed in the US for over 200 years. Studies suggest that advertising has an impact on the initiation and maintenance of smoking behaviors. In recent years, electronic cigarettes (e-cigarettes) emerged on the market as an alternative to the traditional tobacco cigarette. The purpose of this study was to describe advertisements in popular US magazines marketed to women for cigarettes and e-cigarettes. Methods: This study involved analyzing 99 issues of 14 popular US magazines marketed to women. Results: Compared to advertisements for traditional cigarettes, advertisements for e-cigarettes were more often found in magazines geared toward the 31–40-year-old audience (76.5% vs. 53.1%, P = 0.011) whereas traditional cigarette advertisements were nearly equally distributed among women 31–40 and ≥40 years. More than three-quarters of the e-cigarette advertisements presented in magazines aimed at the higher median income households compared to a balanced distribution by income for traditional cigarettes (P = 0.033). Conclusions: Future studies should focus on specific marketing tactics used to promote e-cigarette use as this product increases in popularity, especially among young women smokers. PMID:27688867

  14. Using Alcohol to Sell Cigarettes to Young Adults: A Content Analysis of Cigarette Advertisements

    ERIC Educational Resources Information Center

    Belstock, Sarah A.; Connolly, Gregory N.; Carpenter, Carrie M.; Tucker, Lindsey

    2008-01-01

    Objective: Advertising influences the health-related behaviors of college-aged individuals. Cigarette manufacturers aggressively market to young adults and may exploit their affinity for alcohol when creating advertisements designed to increase cigarettes' appeal. Internal tobacco industry documents reveal that cigarette manufacturers understood…

  15. Tiotropium bromide exerts anti-inflammatory activity in a cigarette smoke mouse model of COPD.

    PubMed

    Wollin, L; Pieper, M P

    2010-08-01

    Tiotropium bromide is a long acting muscarinic antagonist (LAMA), marketed under the brand name Spiriva, for the treatment of chronic obstructive pulmonary disease (COPD). Besides its proven direct bronchodilatory activity, recent clinical studies demonstrated that tiotropium is able to reduce the exacerbation rate and impact the clinical course of COPD. One significant pathological feature believed to be causative for the progressive nature of COPD is chronic pulmonary inflammation. The aim of the present study was to investigate the anti-inflammatory activity of tiotropium on cigarette smoke-induced pulmonary inflammation in mice. C57Bl/6 mice were exposed to cigarette smoke (CS) for four days with increasing exposure time for up to 6h per day to elicit pulmonary inflammation and mediator release. One hour before smoke exposure, animals were treated with tiotropium by inhalation (0.01-0.3mg/mL) for 5 min; 18h after the last CS exposure a bronchoalveolar lavage was performed. Tiotropium concentration-dependently inhibited pulmonary neutrophilic inflammation with an IC(50) of 0.058 mg/mL and a maximum inhibition of 60% at 0.3mg/mL. Furthermore, the CS-induced pulmonary release of leukotriene B(4), interleukin-6, keratinocyte-derived chemokine, monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha and -2, and tumor necrosis factor alpha was dose-dependently reduced. The bronchodilatory activity of tiotropium against acetycholine-induced bronchoconstriction was found to be in the same dose range as the anti-inflammatory activity with an IC(50) of 0.045 mg/mL and a maximum bronchodilation of 90% at 0.3mg/mL. Our data suggest that the beneficial effects of tiotropium on the course of COPD shown in patients may be associated with an anti-inflammatory activity.

  16. Hazardous waste status of discarded electronic cigarettes.

    PubMed

    Krause, Max J; Townsend, Timothy G

    2015-05-01

    The potential for disposable electronic cigarettes (e-cigarettes) to be classified as hazardous waste was investigated. The Toxicity Characteristic Leaching Procedure (TCLP) was performed on 23 disposable e-cigarettes in a preliminary survey of metal leaching. Based on these results, four e-cigarette products were selected for replicate analysis by TCLP and the California Waste Extraction Test (WET). Lead was measured in leachate as high as 50mg/L by WET and 40mg/L by TCLP. Regulatory thresholds were exceeded by two of 15 products tested in total. Therefore, some e-cigarettes would be toxicity characteristic (TC) hazardous waste but a majority would not. When disposed in the unused form, e-cigarettes containing nicotine juice would be commercial chemical products (CCP) and would, in the United States (US), be considered a listed hazardous waste (P075). While household waste is exempt from hazardous waste regulation, there are many instances in which such waste would be subject to regulation. Manufactures and retailers with unused or expired e-cigarettes or nicotine juice solution would be required to manage these as hazardous waste upon disposal. Current regulations and policies regarding the availability of nicotine-containing e-cigarettes worldwide were reviewed. Despite their small size, disposable e-cigarettes are consumed and discarded much more quickly than typical electronics, which may become a growing concern for waste managers.

  17. Price and cigarette consumption in Europe

    PubMed Central

    Gallus, S; Schiaffino, A; Vecchia, C La; Townsend, J; Fernandez, E

    2006-01-01

    Objective To analyse the variation in demand for tobacco according to price of cigarettes across the European region. Design Cross‐sectional study. Setting All the 52 countries of the European region. Participants For each European country, data were collected on annual per adult cigarette consumption (2000), smoking prevalence (most recent), retail price of a pack of local and foreign brand cigarettes (around 2000), the gross domestic product adjusted by purchasing power parities, and the adult population (2000). Main outcome measure Price elasticity of demand for cigarettes (that is, the change in cigarette consumption according to a change in tobacco price) across all the European countries, estimated by double‐log multiple linear regression. Results Controlling for male to female prevalence ratio, price elasticities for consumption were −0.46 (95% confidence interval (CI) −0.74 to −0.17) and −0.74 (95% CI −1.13 to −0.35) for local and foreign brand, respectively. The inverse relation between cigarette price and consumption was stronger in countries not in the European Union (price elasticity for foreign brand cigarettes of −0.8) as compared to European Union countries (price elasticity of −0.4). Conclusions The result that, on average, in Europe smoking consumption decreases 5–7% for a 10% increase in the real price of cigarettes strongly supports an inverse association between price and cigarette smoking. PMID:16565459

  18. 75 FR 75936 - Required Warnings for Cigarette Packages and Advertisements; Research Report

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... Cigarette Packages and Advertisements; Research Report AGENCY: Food and Drug Administration, HHS. ACTION... warnings and accompanying graphics to be displayed on cigarette packages and in cigarette advertisements... health warning statements appear on cigarette packages and in cigarette advertisements. Section 201...

  19. Cigarette smoke extract-induced proliferation of normal human urothelial cells via the MAPK/AP-1 pathway

    PubMed Central

    Geng, Hao; Zhao, Li; Liang, Zhaofeng; Zhang, Zhiqiang; Xie, Dongdong; Bi, Liangkuan; Wang, Yi; Zhang, Tao; Cheng, Lei; Yu, Dexin; Zhong, Caiyun

    2017-01-01

    Bladder cancer (BC) is universally acknowledged as a significant public health issue, worldwide. Numerous studies have demonstrated that cigarette smoke is the primary risk factor for BC. However, the mechanism of cigarette smoke-induced BC has not been fully elucidated. Sustained epithelial cell hyperplasia has been identified as a preneoplastic lesion during the formation of BC. The aim of the present study was to investigate whether exposure to cigarette smoke extract (CSE) induced proliferation in normal human urothelial SV-HUC-1 cells. Furthermore, the role of the mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) pathway in the CSE-induced proliferation of SV-HUC-1 cells was also investigated. The present study revealed that the expression of phosphorylated-extracellular signal regulated protein kinase (ERK)1/2, Jun N-terminal kinase (JNK) and p38 was significantly increased following exposure to CSE in SV-HUC-1 cells. Furthermore, CSE increased the expression of the proliferation markers, cyclin D1 and proliferating cell nuclear antigen. By contrast, CSE attenuated the expression of p21. In addition, the inhibitors of ERK1/2 and JNK reversed the aforementioned effects of CSE. However, p38 inhibition did not reverse CSE-induced proliferation. In conclusion, the results of the present study demonstrated that exposure to CSE induced proliferation in normal human urothelial cells. Furthermore, the results also indicated that the ERK1/2 and JNK pathways are important for the regulation of proliferation via the AP-1 proteins. PMID:28123584

  20. Cigarette litter: smokers' attitudes and behaviors.

    PubMed

    Rath, Jessica M; Rubenstein, Rebecca A; Curry, Laurel E; Shank, Sarah E; Cartwright, Julia C

    2012-06-01

    Cigarette butts are consistently the most collected items in litter clean-up efforts, which are a costly burden to local economies. In addition, tobacco waste may be detrimental to our natural environment. The tobacco industry has conducted or funded numerous studies on smokers' littering knowledge and behavior, however, non-industry sponsored research is rare. We sought to examine whether demographics and smokers' knowledge and beliefs toward cigarette waste as litter predicts littering behavior. Smokers aged 18 and older (n = 1,000) were interviewed about their knowledge and beliefs towards cigarette waste as litter. Respondents were members of the Research Now panel, an online panel of over three million respondents in the United States. Multivariate logistic regressions were conducted to determine factors significantly predictive of ever having littered cigarette butts or having littered cigarette butts within the past month (p-value < 0.05). The majority (74.1%) of smokers reported having littered cigarette butts at least once in their life, by disposing of them on the ground or throwing them out of a car window. Over half (55.7%) reported disposing of cigarette butts on the ground, in a sewer/gutter, or down a drain in the past month. Those who did not consider cigarette butts to be litter were over three and half times as likely to report having ever littered cigarette butts (OR = 3.68, 95%CI = 2.04, 6.66) and four times as likely to have littered cigarette butts in the past month (OR = 4.00, 95%CI = 2.53, 6.32). Males were significantly more likely to have littered cigarette butts in the past month compared to females (OR = 1.49, 95%CI = 1.14, 1.94). Holding the belief that cigarette butts are not litter was the only belief in this study that predicted ever or past-month littering of cigarette waste. Messages in anti-cigarette-litter campaigns should emphasize that cigarette butts are not just litter but are toxic waste and are harmful when disposed of

  1. Cigarette Litter: Smokers’ Attitudes and Behaviors

    PubMed Central

    Rath, Jessica M.; Rubenstein, Rebecca A.; Curry, Laurel E.; Shank, Sarah E.; Cartwright, Julia C.

    2012-01-01

    Cigarette butts are consistently the most collected items in litter clean-up efforts, which are a costly burden to local economies. In addition, tobacco waste may be detrimental to our natural environment. The tobacco industry has conducted or funded numerous studies on smokers’ littering knowledge and behavior, however, non-industry sponsored research is rare. We sought to examine whether demographics and smokers’ knowledge and beliefs toward cigarette waste as litter predicts littering behavior. Smokers aged 18 and older (n = 1,000) were interviewed about their knowledge and beliefs towards cigarette waste as litter. Respondents were members of the Research Now panel, an online panel of over three million respondents in the United States. Multivariate logistic regressions were conducted to determine factors significantly predictive of ever having littered cigarette butts or having littered cigarette butts within the past month (p-value < 0.05). The majority (74.1%) of smokers reported having littered cigarette butts at least once in their life, by disposing of them on the ground or throwing them out of a car window. Over half (55.7%) reported disposing of cigarette butts on the ground, in a sewer/gutter, or down a drain in the past month. Those who did not consider cigarette butts to be litter were over three and half times as likely to report having ever littered cigarette butts (OR = 3.68, 95%CI = 2.04, 6.66) and four times as likely to have littered cigarette butts in the past month (OR = 4.00, 95%CI = 2.53, 6.32). Males were significantly more likely to have littered cigarette butts in the past month compared to females (OR = 1.49, 95%CI = 1.14, 1.94). Holding the belief that cigarette butts are not litter was the only belief in this study that predicted ever or past-month littering of cigarette waste. Messages in anti-cigarette-litter campaigns should emphasize that cigarette butts are not just litter but are toxic waste and are harmful when disposed of

  2. Narrative review of genes, environment, and cigarettes.

    PubMed

    Do, Elizabeth; Maes, Hermine

    2016-08-01

    Tobacco use remains the leading cause of preventable death in the US, emphasizing the need to understand which genes and environments are involved in the establishment of cigarette use behaviors. However, to date, no comprehensive review of the influence of genes, the environment, and their interaction on cigarette use exists. This narrative review provides a description of gene variants and environmental factors associated with cigarette use, as well as an overview of studies investigating gene-environment interaction (GxE) in cigarette use. GxE studies of cigarette use have been useful in demonstrating that the influence of genes changes as a function of both the phenotype being measured and the environment. However, it is difficult to determine how the effect of genes contributing to different phenotypes of cigarette use changes as a function of the environment. This suggests the need for more studies of GxE, to parse out the effects of genes and the environment across the development of cigarette use phenotypes, which may help to inform potential prevention and intervention efforts aimed at reducing the prevalence of cigarette use. Key Messages No comprehensive reviews of the influence of genes, the environment, and their interaction on cigarette use exist currently. The influence of genes may change as a function of the environment and the phenotype being measured. It is difficult to determine how the effect of genes contributing to different phenotypes of cigarette use changes according to environmental context, suggesting the need for more studies of gene-environment interaction related to cigarette use to parse out effects.

  3. Hazardous waste status of discarded electronic cigarettes

    SciTech Connect

    Krause, Max J.; Townsend, Timothy G.

    2015-05-15

    Highlights: • Electronic cigarettes were tested using TCLP and WET. • Several electronic cigarette products leached lead at hazardous waste levels. • Lead was the only element that exceeded hazardous waste concentration thresholds. • Nicotine solution may cause hazardous waste classification when discarded unused. - Abstract: The potential for disposable electronic cigarettes (e-cigarettes) to be classified as hazardous waste was investigated. The Toxicity Characteristic Leaching Procedure (TCLP) was performed on 23 disposable e-cigarettes in a preliminary survey of metal leaching. Based on these results, four e-cigarette products were selected for replicate analysis by TCLP and the California Waste Extraction Test (WET). Lead was measured in leachate as high as 50 mg/L by WET and 40 mg/L by TCLP. Regulatory thresholds were exceeded by two of 15 products tested in total. Therefore, some e-cigarettes would be toxicity characteristic (TC) hazardous waste but a majority would not. When disposed in the unused form, e-cigarettes containing nicotine juice would be commercial chemical products (CCP) and would, in the United States (US), be considered a listed hazardous waste (P075). While household waste is exempt from hazardous waste regulation, there are many instances in which such waste would be subject to regulation. Manufactures and retailers with unused or expired e-cigarettes or nicotine juice solution would be required to manage these as hazardous waste upon disposal. Current regulations and policies regarding the availability of nicotine-containing e-cigarettes worldwide were reviewed. Despite their small size, disposable e-cigarettes are consumed and discarded much more quickly than typical electronics, which may become a growing concern for waste managers.

  4. HIF-1α Plays a Critical Role in the Gestational Sidestream Smoke-Induced Bronchopulmonary Dysplasia in Mice

    PubMed Central

    Singh, Shashi P.; Chand, Hitendra S.; Gundavarapu, Sravanthi; Saeed, Ali Imran; Langley, Raymond J.; Tesfaigzi, Yohannes; Mishra, Neerad C.; Sopori, Mohan L.

    2015-01-01

    Rationale Smoking during pregnancy increases the risk of bronchopulmonary dysplasia (BPD) and, in mice, gestational exposure to sidestream cigarette smoke (SS) induces BPD-like condition characterized by alveolar simplification, impaired angiogenesis, and suppressed surfactant protein production. Normal fetal development occurs in a hypoxic environment and nicotinic acetylcholine receptors (nAChRs) regulate the hypoxia-inducible factor (HIF)-1α that controls apoptosis and angiogenesis. To understand SS-induced BPD, we hypothesized that gestational SS affected alveolar development through HIF-1α. Methods Pregnant BALB/c mice were exposed to air (control) or SS throughout the gestational period and the 7-day-old lungs of the progeny were examined. Results Gestational SS increased apoptosis of alveolar and airway epithelial cells. This response was associated with increased alveolar volumes, higher levels of proapoptotic factors (FOXO3a, HIPK2, p53, BIM, BIK, and BAX) and the antiangiogenic factor (GAX), and lower levels of antiapoptotic factors (Akt-PI3K, NF-κB, HIF-1α, and Bcl-2) in the lung. Although gestational SS increased the cells containing the proangiogenic bombesin-like-peptide, it markedly decreased the expression of its receptor GRPR in the lung. The effects of SS on apoptosis were attenuated by the nAChR antagonist mecamylamine. Conclusions Gestational SS-induced BPD is potentially regulated by nAChRs and associated with downregulation of HIF-1α, increased apoptosis of epithelial cells, and increased alveolar volumes. Thus, in mice, exposure to sidestream tobacco smoke during pregnancy promotes BPD-like condition that is potentially mediated through the nAChR/HIF-1α pathway. PMID:26361040

  5. Protection of erdosteine on smoke-induced peripheral neutrophil dysfunction both in healthy and in bronchitic smokers.

    PubMed

    Ciaccia, A; Papi, A; Tschirky, B; Fregnan, B

    1992-01-01

    The purpose of the present study was to determine whether erdosteine and its metabolites (substances containing thiol groups) can prevent the alteration of the chemotactic function of polymorphonuclear cells (PMN) from peripheral blood induced by cigarette smoke of eight healthy non-smoking volunteers, when incubated in vitro before smoke exposure, and whether oral treatment with erdosteine (900 mg/day) for two weeks might restore the chemotaxis of PMN, either from eight healthy or from 16 chronic bronchitic smokers. The chemotactic stimuli in vitro were casein, lipopolysaccharides (LPS), and formyl-methionyl-leucyl-phenyalanine (FMLP). The results of the study in vitro have confirmed that PMN from non-smoking volunteers shows a reduced chemotactic responsiveness when exposed in vitro to smoke. This can be partially prevented in a dose-related manner by pre-incubation with erdosteine, its metabolites, cysteine, and glutathione (metabolites I and II being at least 10 times more active than the intact substance and the known biological standards also containing thiol groups). The experiment on PMN from healthy smokers (in a double-blind crossover design versus placebo) has indicated that the chemotaxis can be improved only after treatment with erdosteine. The same observation has been made in the experiment on PMN from smokers affected by chronic bronchitis (in a double-blind design versus placebo with two distinct groups). In these patients the phagocytic and bactericidal activities of PMN were not affected by the smoke and therefore, neither one was influenced by erdosteine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Smokers' and E-Cigarette Users' Perceptions about E-Cigarette Warning Statements.

    PubMed

    Wackowski, Olivia A; Hammond, David; O'Connor, Richard J; Strasser, Andrew A; Delnevo, Cristine D

    2016-06-30

    Cigarette warning labels are important sources of risk information, but warning research for other tobacco products is limited. This study aimed to gauge perceptions about warnings that may be used for e-cigarettes. We conducted six small focus groups in late 2014/early 2015 with adult current e-cigarette users and cigarette-only smokers. Participants rated and discussed their perceptions of six e-cigarette warning statements, and warnings in two existing Vuse and MarkTen e-cigarette ads. Participants were open to e-cigarette warnings and provided the strongest reactions to statements warning that e-liquid/e-vapor or e-cigarettes can be poisonous, contain toxins, or are "not a safe alternative to smoking". However, many also noted that these statements were exaggerated, potentially misleading, and could scare smokers away from reducing their harm by switching to e-cigarettes. Opinions on the Food and Drug Administration's proposed nicotine addiction warning and warnings that e-cigarettes had not been approved for smoking cessation or had unknown health effects were mixed. Participants perceived MarkTen's advertisement warning to be stronger and more noticeable than Vuse's. Care should be taken in developing e-cigarette warnings given their relative recentness and potential for harm reduction compared to other tobacco products. Additional research, including with varied audiences, would be instructive.

  7. Smokers’ and E-Cigarette Users’ Perceptions about E-Cigarette Warning Statements

    PubMed Central

    Wackowski, Olivia A.; Hammond, David; O’Connor, Richard J.; Strasser, Andrew A.; Delnevo, Cristine D.

    2016-01-01

    Cigarette warning labels are important sources of risk information, but warning research for other tobacco products is limited. This study aimed to gauge perceptions about warnings that may be used for e-cigarettes. We conducted six small focus groups in late 2014/early 2015 with adult current e-cigarette users and cigarette-only smokers. Participants rated and discussed their perceptions of six e-cigarette warning statements, and warnings in two existing Vuse and MarkTen e-cigarette ads. Participants were open to e-cigarette warnings and provided the strongest reactions to statements warning that e-liquid/e-vapor or e-cigarettes can be poisonous, contain toxins, or are “not a safe alternative to smoking”. However, many also noted that these statements were exaggerated, potentially misleading, and could scare smokers away from reducing their harm by switching to e-cigarettes. Opinions on the Food and Drug Administration’s proposed nicotine addiction warning and warnings that e-cigarettes had not been approved for smoking cessation or had unknown health effects were mixed. Participants perceived MarkTen’s advertisement warning to be stronger and more noticeable than Vuse’s. Care should be taken in developing e-cigarette warnings given their relative recentness and potential for harm reduction compared to other tobacco products. Additional research, including with varied audiences, would be instructive. PMID:27376310

  8. A review on engineering of cellulosic cigarette paper to reduce carbon monoxide delivery of cigarettes.

    PubMed

    Shen, Jing; Li, Jinsong; Qian, Xueren; Ren, Wanshan; Fatehi, Pedram

    2014-01-30

    In cigarette production, the cellulosic paper essentially derived from flax fibers or other fiber materials is used as the wrapping material. During smoking of cigarettes, the highly toxic carbon monoxide is produced. To decrease the amount of carbon monoxide emission in the mainstream smoke, the engineering of all cigarette components including cellulosic cigarette paper and tobacco column is critical. This review summarizes the concepts related to engineering of cigarette paper. These mainly include permeability control, increased use of burn additives, optimization of fiber basis weight, engineering of calcium carbonate fillers, and incorporation of catalysts/oxidants. In particular, catalytic and/or oxidative conversion of carbon monoxide to carbon dioxide has been very widely reported. The control of permeability/diffusivity of cigarette paper is also of critical importance for enhanced diffusion of carbon monoxide out of the cigarette. The development of new concepts and combination of various concepts may lead to breakthroughs in this area.

  9. Cigarette ignition of soft furnishings: A literature review with commentary

    NASA Astrophysics Data System (ADS)

    Krasny, John F.

    1987-04-01

    Literature pertinent to the ignition by smoldering cigarettes of upholstered furniture and mattresses (soft furnishings) was searched through early 1986. This included literature on the smoldering behavior of cigarettes in air; their behavior on a variety of substrates simulating soft furnishings; mechanism of smoldering in substrates; relative cigarette ignition resistance of substrates; and relative propensity of commercial cigarette packings to ignite substrates. According to the reviewed literature, the smoldering behavior of cigarettes on substrates differs from that of cigarettes burning in air: on substrates, cigarette temperatures tend to be lower, and burning rates slower. These differences seem to be larger for substrates which ignite than for those which self-extinguish after the cigarette burns out. The characteristics of soft furnishings which insure resistance to cigarette ignition have been established, but those of cigarettes with low propensity to ignite furnishings have not. No mathematical model has been reported for the interaction of cigarette and substrate, but some empirical data do exist.

  10. 47 CFR 73.4055 - Cigarette advertising.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Cigarette advertising. 73.4055 Section 73.4055 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4055 Cigarette advertising. See 15 U.S.C. 1335....

  11. 47 CFR 73.4055 - Cigarette advertising.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Cigarette advertising. 73.4055 Section 73.4055 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4055 Cigarette advertising. See 15 U.S.C. 1335....

  12. 47 CFR 73.4055 - Cigarette advertising.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Cigarette advertising. 73.4055 Section 73.4055 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4055 Cigarette advertising. See 15 U.S.C. 1335....

  13. 47 CFR 73.4055 - Cigarette advertising.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Cigarette advertising. 73.4055 Section 73.4055 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4055 Cigarette advertising. See 15 U.S.C. 1335. [44...

  14. 47 CFR 73.4055 - Cigarette advertising.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Cigarette advertising. 73.4055 Section 73.4055 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4055 Cigarette advertising. See 15 U.S.C. 1335....

  15. Debate, Research on E-Cigarettes Continues

    Cancer.gov

    Since they first began to be sold in North America in the mid-2000s, electronic cigarettes have been the subject of intense debate. NCI's Dr. Michele Bloch recently presented an update on some of the issues surrounding e-cigarettes.

  16. Cigarette advertising and adolescent experimentation with smoking.

    PubMed

    Klitzner, M; Gruenewald, P J; Bamberger, E

    1991-03-01

    The extent to which cigarette advertising contributes to increases in smoking has been debated by public health professionals and the tobacco industry. One aspect of this debate has been the degree to which advertising influences smoking among adolescents. Previous research suggests that there are significant relationships between measures of advertising and smoking. However, potential simultaneous relationships between these measures have not been addressed. Observed correlations may arise from the effects of advertising on smoking or from smokers' selective exposure to advertisements. This study examined relationships between cigarette advertising and smoking experimentation. Using environmental and psychological measures of advertising exposure, it was demonstrated that adolescents who experimented with cigarettes were better able to recognize advertised products than those who had not, a selective exposure effect. Conversely, subjects who were better at recognizing advertised brands were more likely to have experimented with cigarettes, an effect due to their exposure to cigarette advertising.

  17. Electronic cigarettes: ambiguity and controversies of usage.

    PubMed

    Savant, Suyog; Shetty, Deeksha; Phansopkar, Sushil; Jamkhande, Amol

    2014-04-01

    Electronic cigarettes (EC), a proxy to conventional cigarettes, gained popularity on the basis of its own advocacy, marketing and large scale publicity. Sometimes marketed as an adjunct to quitting or a substitute for cigarettes, its popularity rose. However, its sale in the global markets was subjected to prejudice. Reasons cited by the regulatory bodies for its ouster were the toxic contents it contained. Some countries preferred to ban them while some have legalised them. However, the manufacturers have claimed that it does have the potential to help smokers quit or at least replace the conventional cigarettes which cause millions of death globally. Research is hence needed to prove the efficacy and utility of this device for welfare of people who are looking for better options than puffing cigarettes.

  18. Carbon monoxide kinetics following simulated cigarette smoking

    SciTech Connect

    Karnik, A.S.; Coin, E.J.

    1980-05-01

    Carbon monoxide kinetics were measured in the blood (% carboxyhemoglobin) and alveolar phase (ppM carbon monoxide) after simulated cigarette smoking. Cigarette smoking was siumlated using the same amount of carbon monoxide that 2R1F cigarettes manufactured by the Tobacco Research Institute would contain. Ten boluses of air containing carbon monoxide equivalent to smoking one cigarette were inhaled by six healthy nonsmoker volunteers. Carbon monoxide in the air phase was measured by an Ecolyzer and carboxyhemoglobin was measured by a CO-Oximeter. The mean rise in alveolar carbon monoxide immediately and 20 min after inhaling the last bolus was 3.3 and 3.1 ppM, respectively (p<.005). The mean rise in carboxyhemoglobin immediately and 20 min after inhalation of the last bolus was 0.8 and 0.5% respectively (P<.005). The changes in carboxyhemoglobin were found to be similar to changes that occur when one cigarette is actually smoked.

  19. Do electronic cigarettes help with smoking cessation?

    PubMed

    2014-11-01

    Smoking causes around 100,000 deaths each year in the UK, and is the leading cause of preventable disease and early mortality. Smoking cessation remains difficult and existing licensed treatments have limited success. Nicotine addiction is thought to be one of the primary reasons that smokers find it so hard to give up, and earlier this year DTB reviewed the effects of nicotine on health. Electronic cigarettes (e-cigarettes) are nicotine delivery devices that aim to mimic the process of smoking but avoid exposing the user to some of the harmful components of traditional cigarettes. However, the increase in the use of e-cigarettes and their potential use as an aid to smoking cessation has been subject to much debate. In this article we consider the regulatory and safety issues associated with the use of e-cigarettes, and their efficacy in smoking cessation and reduction.

  20. Tobacco Smoke-Induced Hepatic Injury with Steatosis, Inflammation, and Impairments in Insulin and Insulin-Like Growth Factor Signaling

    PubMed Central

    de la Monte, Suzanne M.; Tong, M; Agarwal, AR; Cadenas, E

    2016-01-01

    Background Alcoholic liver disease (ALD) is associated with impairments in hepatic insulin and insulin-like growth factor (IGF) signaling through cell growth, survival, and metabolic pathways. Since not all heavy drinkers develop ALD, co-factors may be important. Epidemiologic data indicate that most heavy drinkers smoke tobacco and experimental data revealed that low-level nitrosamine exposures, including those from tobacco, can cause steatohepatitis with hepatic insulin/IGF resistance and exacerbate ALD. We hypothesize that cigarette smoke (CS) exposures also cause liver injury with impaired hepatic insulin/IGF signaling, and thereby contribute to ALD. Methods Adult male A/J mice were exposed to air for 8 weeks (A8), CS for 4 (CS4) or 8 (CS8) weeks, or CS for 8 weeks with 2 weeks recovery (CS8+R). Results CS exposures caused progressive liver injury with disruption of the normal hepatic chord architecture, lobular inflammation, apoptosis or necrosis, micro-steatosis, sinusoidal dilatation, and nuclear pleomorphism. Histopathological liver injury scores increased significantly from A8 to CS4 and then further to CS8 (P<0.0001). The mean histological grade was also higher in CS8+R relative to A8 (P<0.0001) but lower than in CS4, reflecting partial resolution of injury by CS withdrawal. CS exposures impaired insulin and IGF-1 signaling through IRS-1, Akt, GSK-3β, and PRAS40. Livers from CS8+R mice had normalized or elevated levels of insulin receptor, pYpY-Insulin-R, 312S-IRS-1, 473S-Akt, S9-GSK-3β, and pT246-PRAS40 relative to A8, CS4, or CS8, reflecting partial recovery. Conclusion CS-mediated liver injury and steatohepatitis with impairments in insulin/IGF signalling are reminiscent of the findings in ALD. Therefore, CS exposures (either first or second-hand) may serve as a co-factor in ALD. The persistence of several abnormalities following CS exposure cessation suggests that some aspects of CS-mediated hepatic metabolic dysfunction are not readily reversible

  1. Heme oxygenase-1 gene expression in human alveolar epithelial cells (A549) following exposure to whole cigarette smoke on a direct in vitro exposure system.

    PubMed

    Fukano, Yasuo; Yoshimura, Hiroyuki; Yoshida, Takemi

    2006-07-01

    Many in vitro studies have employed cigarette smoke condensates or soluble smoke components to investigate the biological effects of cigarette smoke. However, neither of these methods evaluates the biological effects of fresh whole cigarette smoke. It is most desirable to conduct in vitro biological studies under conditions which accommodate the dynamic physicochemical character of fresh cigarette smoke. Previously we reported the development of a whole smoke exposure system to assess the biological effects of mainstream cigarette smoke. The exposure system design was based on a combination of the sedimentation procedure and the CULTEX cultivation technique, which includes a systemized air/liquid interface methodology and exposes the cells to fresh smoke at every puff. The aim of this study was to adopt the other biological endpoint to our whole smoke exposure system. We focused on heme oxygenase (HO)-1 mRNA gene expression, an enzyme which has recently been shown to be highly responsible for oxidative stress. In the present study, a dose-response relationship between the HO-1 mRNA expression based on the reverse transcription real-time PCR method and total exposure to cigarette smoke was observed. When a Cambridge filter pad was placed between the cigarette and exposure module, to ensure the cells were only exposed to the gas/vapor phase, the latter, as well as the whole smoke, induced HO-1 mRNA dose dependently. For the next step, acetate plain and charcoal filters with the same pressure drop were prepared to assess the potential ability of charcoal filters with regard to the vapor phase performance. The results revealed reduced HO-1 mRNA gene expression when a charcoal filter was used. Direct whole smoke exposure is a significant approach and may reflect the conditions of exposure essentially resulting from direct contact between cells and a dynamic mixture of gaseous and particulate constituents. We were able to adopt a gene expression assay for oxidative

  2. Cigarette smoking and breast cancer.

    PubMed

    Baron, J A; Newcomb, P A; Longnecker, M P; Mittendorf, R; Storer, B E; Clapp, R W; Bogdan, G; Yuen, J

    1996-05-01

    A priori hypotheses suggest that cigarette smoking could either increase or decrease breast cancer incidence. To clarify these competing hypotheses, we used data from a very large population-based breast cancer case-control study to investigate the impact of smoking on breast cancer risk. Breast cancer patients less than 75 years old were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire; controls were randomly selected from driver's license lists (age less than 65) or lists of Medicare beneficiaries (age 65-74). Information on reproductive history, medical history, and personal habits including cigarette smoking was obtained by telephone interview. A total of 6,888 cases and 9,529 controls were interviewed. There was virtually no relationship between current smoking and breast cancer risk (multivariate odds ratio, 1.00; 95% confidence interval, 0.92-1.09), and former smokers had a barely increased risk (odds ratio, 1.10; 95% confidence interval, 1.01-1.19). Similar results were observed among both premenopausal and postmenopausal women. There was no suggestion that heavy or long-term smoking increased or decreased risk, nor were there indications that women who began smoking at an early age were at increased risk, as has been hypothesized. The results of this large population-based study indicate that smoking does not influence the risk of breast cancer, even among heavy smokers who began smoking at an early age.

  3. Health Education and Cigarette Smoking

    PubMed Central

    Morison, James B.; Medovy, Herry; MacDonell, Gordon T.

    1964-01-01

    The smoking habits of Winnipeg school students were surveyed before and after a three-year program of health education on the hazards of smoking, directed to 8300 out of 48,000 students. The program consisted of informal approaches to students in elementary schools and a formal program of talks, lectures, films, and student participation for older students. There were fewer students at all ages who had never smoked a cigarette at the time of the second survey. There was a slight decrease in the number of regular smokers in high school, most marked in the school where the program was enthusiastically received and student participation was most active. A direct relationship between parental smoking and that of the student, and an inverse relationship between academic achievement and student smoking, were shown on both surveys. The majority of students believed that smoking caused lung cancer and other hazards to health, although this was less marked among smokers. The results indicated that an intensive program of health education directed to the teenagers in school was a potentially useful approach to the problem of cigarette smoking. PMID:14154295

  4. [Preliminary influence of 2015 cigarette excise tax up-regulation on cigarette retail price].

    PubMed

    Feng, G Z; Wang, C X; Yang, J Q; Jiang, Y

    2016-10-10

    Objective: To evaluate the impact of cigarette excise tax up-regulation on the retail price of cigarettes in 2015. Methods: Nominal and real price of selected cigarette varieties were calculated with data from Tobacco Retail Price Monitoring Project, which was conducted in 10 cities of China from 2013 to 2015. The trend of the cigarette prices changing was analyzed with annual data. Results: A total of 352 varieties of cigarettes were surveyed during the three years. The nominal price of these cigarettes did not change significantly from 2013 to 2014. Compared with nominal price of 2014, the price of 286 varieties increased and the price of 10 most popular varieties increased from 0.6% to 7.4% after cigarette excise tax increased, but the actual prices had both rise and fall compared with 2013. Conclusions: Cigarette excise tax raise in 2015 had influence on the retail price of cigarettes. But the increase in retail price was very limited, if factors including inflation and purchasing power are taken into consideration. Therefore, the influence of 2015 cigarette excise tax raise on tobacco control needs further evaluation.

  5. Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol.

    PubMed

    Neilson, Louise; Mankus, Courtney; Thorne, David; Jackson, George; DeBay, Jason; Meredith, Clive

    2015-10-01

    Development of physiologically relevant test methods to analyse potential irritant effects to the respiratory tract caused by e-cigarette aerosols is required. This paper reports the method development and optimisation of an acute in vitro MTT cytotoxicity assay using human 3D reconstructed airway tissues and an aerosol exposure system. The EpiAirway™ tissue is a highly differentiated in vitro human airway culture derived from primary human tracheal/bronchial epithelial cells grown at the air-liquid interface, which can be exposed to aerosols generated by the VITROCELL® smoking robot. Method development was supported by understanding the compatibility of these tissues within the VITROCELL® system, in terms of airflow (L/min), vacuum rate (mL/min) and exposure time. Dosimetry tools (QCM) were used to measure deposited mass, to confirm the provision of e-cigarette aerosol to the tissues. EpiAirway™ tissues were exposed to cigarette smoke and aerosol generated from two commercial e-cigarettes for up to 6 h. Cigarette smoke reduced cell viability in a time dependent manner to 12% at 6 h. E-cigarette aerosol showed no such decrease in cell viability and displayed similar results to that of the untreated air controls. Applicability of the EpiAirway™ model and exposure system was demonstrated, showing little cytotoxicity from e-cigarette aerosol and different aerosol formulations when compared directly with reference cigarette smoke, over the same exposure time.

  6. 27 CFR 40.23 - Cigarette tax rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Cigarette tax rates. 40.23... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes § 40.23 Cigarette tax rates. Cigarettes are taxed at the following rates under 26...

  7. 27 CFR 41.74 - Notice for cigarettes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Notice for cigarettes. 41..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Packages § 41.74 Notice for cigarettes. Every package of cigarettes, except...

  8. 27 CFR 40.23 - Cigarette tax rates.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Cigarette tax rates. 40.23... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes § 40.23 Cigarette tax rates. Cigarettes are taxed at the following rates under 26...

  9. 27 CFR 41.32 - Cigarette tax rates.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Cigarette tax rates. 41.32... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.32 Cigarette tax rates. Cigarettes are taxed at the following...

  10. 27 CFR 40.215 - Notice for cigarettes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Notice for cigarettes. 40..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES... cigarettes. Every package of cigarettes shall, before removal subject to tax, have adequately...

  11. 19 CFR 10.65 - Cigars and cigarettes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Cigars and cigarettes. 10.65 Section 10.65 Customs... Equipment for Vessels § 10.65 Cigars and cigarettes. (a) Imported cigars and cigarettes in bonded warehouse... cigarettes is made up of a number of units, each in a separate package, such units may be...

  12. 27 CFR 40.215 - Notice for cigarettes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Notice for cigarettes. 40..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES... cigarettes. Every package of cigarettes shall, before removal subject to tax, have adequately...

  13. 19 CFR 10.65 - Cigars and cigarettes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Cigars and cigarettes. 10.65 Section 10.65 Customs... Equipment for Vessels § 10.65 Cigars and cigarettes. (a) Imported cigars and cigarettes in bonded warehouse... cigarettes is made up of a number of units, each in a separate package, such units may be...

  14. 27 CFR 41.32 - Cigarette tax rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Cigarette tax rates. 41.32... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.32 Cigarette tax rates. Cigarettes are taxed at the following...

  15. 27 CFR 41.74 - Notice for cigarettes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Notice for cigarettes. 41..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Packages § 41.74 Notice for cigarettes. Every package of cigarettes, except...

  16. 19 CFR 10.65 - Cigars and cigarettes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Cigars and cigarettes. 10.65 Section 10.65 Customs... Equipment for Vessels § 10.65 Cigars and cigarettes. (a) Imported cigars and cigarettes in bonded warehouse... cigarettes is made up of a number of units, each in a separate package, such units may be...

  17. 27 CFR 41.32 - Cigarette tax rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Cigarette tax rates. 41.32... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.32 Cigarette tax rates. Cigarettes are taxed at the following...

  18. 27 CFR 40.215 - Notice for cigarettes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Notice for cigarettes. 40..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES... cigarettes. Every package of cigarettes shall, before removal subject to tax, have adequately...

  19. 27 CFR 40.23 - Cigarette tax rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Cigarette tax rates. 40.23... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes § 40.23 Cigarette tax rates. Cigarettes are taxed at the following rates under 26...

  20. Sources of Cigarettes among Adolescent Smokers: Free or Purchased?

    ERIC Educational Resources Information Center

    Jansen, Paul; Toomey, Traci L.; Nelson, Toben F.; Fabian, Lindsey E. A.; Lenk, Kathleen M.; Forster, Jean L.

    2011-01-01

    Few studies have described youth cigarette sources in terms of whether the cigarettes were free or purchased. Understanding the different ways youth obtain tobacco can guide development of interventions to more effectively reduce youth smoking. Purpose: To determine the propensity for youth to purchase cigarettes versus obtain cigarettes for free,…

  1. 27 CFR 41.74 - Notice for cigarettes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Notice for cigarettes. 41..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Packages § 41.74 Notice for cigarettes. Every package of cigarettes, except...

  2. 27 CFR 40.23 - Cigarette tax rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Cigarette tax rates. 40.23... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes § 40.23 Cigarette tax rates. Cigarettes are taxed at the following rates under 26...

  3. 27 CFR 41.32 - Cigarette tax rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Cigarette tax rates. 41.32... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.32 Cigarette tax rates. Cigarettes are taxed at the following...

  4. 27 CFR 41.32 - Cigarette tax rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Cigarette tax rates. 41.32... OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.32 Cigarette tax rates. Cigarettes are taxed at the following...

  5. 27 CFR 40.23 - Cigarette tax rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Cigarette tax rates. 40.23... OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes § 40.23 Cigarette tax rates. Cigarettes are taxed at the following rates under 26...

  6. 27 CFR 41.74 - Notice for cigarettes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Notice for cigarettes. 41..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Packages § 41.74 Notice for cigarettes. Every package of cigarettes, except...

  7. 19 CFR 10.65 - Cigars and cigarettes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Cigars and cigarettes. 10.65 Section 10.65 Customs... Equipment for Vessels § 10.65 Cigars and cigarettes. (a) Imported cigars and cigarettes in bonded warehouse... cigarettes is made up of a number of units, each in a separate package, such units may be...

  8. 27 CFR 40.215 - Notice for cigarettes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Notice for cigarettes. 40..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES... cigarettes. Every package of cigarettes shall, before removal subject to tax, have adequately...

  9. Patient–physician communication regarding electronic cigarettes

    PubMed Central

    Steinberg, Michael B.; Giovenco, Daniel P.; Delnevo, Cristine D.

    2015-01-01

    Introduction Smokers are likely asking their physicians about the safety of e-cigarettes and their potential role as a cessation tool; however, the research literature on this communication is scant. A pilot study of physicians in the United States was conducted to investigate physician–patient communication regarding e-cigarettes. Methods A total of 158 physicians were recruited from a direct marketing e-mail list and completed a short, web-based survey between January and April 2014. The survey addressed demographics, physician specialty, patient–provider e-cigarette communication, and attitudes towards tobacco harm reduction. Results Nearly two-thirds (65%) of physicians reported being asked about e-cigarettes by their patients, and almost a third (30%) reported that they have recommended e-cigarettes as a smoking cessation tool. Male physicians were significantly more likely to endorse a harm reduction approach. Discussion Physician communication about e-cigarettes may shape patients' perceptions about the products. More research is needed to explore the type of information that physicians share with their patients regarding e-cigarettes and harm reduction. PMID:26844056

  10. Young adult e-cigarette users’ reasons for liking and not liking e-cigarettes: A qualitative study

    PubMed Central

    Herzog, Thaddeus A.; Muranaka, Nicholas; Fagan, Pebbles

    2015-01-01

    Objective To gain an in-depth understanding of what young adult electronic- or e-cigarette users like or dislike about e-cigarettes. We aimed to determine the reasons that may encourage young adults to use e-cigarettes or discourage them from using e-cigarettes. Design Twelve focus group discussions were conducted with 62 current daily e-cigarette users (63% men) of mean age = 25.1 years (Standard Deviation = 5.5). Data were analyzed following principles of inductive content analysis. Results Results indicated 12 categories of reasons for liking e-cigarettes (e.g., recreation, smoking cessation) and 6 categories of reasons for not liking e-cigarettes (e.g., poor product quality, poor smoking experience). Conclusions Young adults’ motives for using or not using e-cigarettes appear to be varied and their relative importance in terms of predicting e-cigarette use initiation, dependence, and cigarette/e-cigarette dual use needs to be carefully studied in population-based, empirical studies. The current findings suggest that e-cigarettes may serve social, recreational, and sensory expectancies that are unique relative to cigarettes and not dependent on nicotine. Further, successful use of e-cigarettes in smoking cessation will likely need higher standards of product quality control, better nicotine delivery efficiency and a counseling component that would teach smokers how to manage e-cigarette devices while trying to quit smoking cigarettes. PMID:26074148

  11. Electronic cigarette aerosol particle size distribution measurements.

    PubMed

    Ingebrethsen, Bradley J; Cole, Stephen K; Alderman, Steven L

    2012-12-01

    The particle size distribution of aerosols produced by electronic cigarettes was measured in an undiluted state by a spectral transmission procedure and after high dilution with an electrical mobility analyzer. The undiluted e-cigarette aerosols were found to have particle diameters of average mass in the 250-450 nm range and particle number concentrations in the 10(9) particles/cm(3) range. These measurements are comparable to those observed for tobacco burning cigarette smoke in prior studies and also measured in the current study with the spectral transmission method and with the electrical mobility procedure. Total particulate mass for the e-cigarettes calculated from the size distribution parameters measured by spectral transmission were in good agreement with replicate determinations of total particulate mass by gravimetric filter collection. In contrast, average particle diameters determined for e-cigarettes by the electrical mobility method are in the 50 nm range and total particulate masses calculated based on the suggested diameters are orders of magnitude smaller than those determined gravimetrically. This latter discrepancy, and the very small particle diameters observed, are believed to result from almost complete e-cigarette aerosol particle evaporation at the dilution levels and conditions of the electrical mobility analysis. A much smaller degree, ~20% by mass, of apparent particle evaporation was observed for tobacco burning cigarette smoke. The spectral transmission method is validated in the current study against measurements on tobacco burning cigarette smoke, which has been well characterized in prior studies, and is supported as yielding an accurate characterization of the e-cigarette aerosol particle size distribution.

  12. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review

    PubMed Central

    Polosa, Riccardo

    2014-01-01

    Electronic cigarettes are a recent development in tobacco harm reduction. They are marketed as less harmful alternatives to smoking. Awareness and use of these devices has grown exponentially in recent years, with millions of people currently using them. This systematic review appraises existing laboratory and clinical research on the potential risks from electronic cigarette use, compared with the well-established devastating effects of smoking tobacco cigarettes. Currently available evidence indicates that electronic cigarettes are by far a less harmful alternative to smoking and significant health benefits are expected in smokers who switch from tobacco to electronic cigarettes. Research will help make electronic cigarettes more effective as smoking substitutes and will better define and further reduce residual risks from use to as low as possible, by establishing appropriate quality control and standards. PMID:25083263

  13. Chinese “Herbal” Cigarettes are as Carcinogenic and Addictive as Regular Cigarettes

    PubMed Central

    Gan, Quan; Yang, Jie; Yang, Gonghuan; Goniewicz, Maciej; Benowitz, Neal L.; Glantz, Stanton A.

    2009-01-01

    Objective To examine the Chinese tobacco industry's claim that herbal cigarettes are less harmful than regular cigarettes. Design Cross-sectional study. Participants 135 herbal cigarette smokers and 143 regular smokers from one city in China completed a questionnaire on smoking behavior and provided a urine sample. Main Outcome Measures Cotinine and trans-3′-hydroxycotinine in all samples and polycyclic aromatic hydrocarbon metabolites (PAHs) (1-hydroxypyrene, naphthols, hydroxyfluorenes and hydroxyphnanthrenes) and the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL) and NNAL-glucuronide in randomly selected 98 samples (47 from the herbal smokers' group and 51 from the regular smokers' group). Values were normalized by creatinine to correct for possible variability introduced by dilution or concentration of the urine. Results Health concern was among the main reasons that smokers switched to herbal cigarettes from regular cigarettes. Smokers reported increased consumption after switching to herbal cigarettes from regular cigarettes. For all the four markers analyzed (cotinine, trans-3′-hydroxycotinine, total NNAL, total PAHs), we observed no significant difference in the levels (p=0.169, p=0.146, p=0.171, p=0.554) between smokers of herbal cigarettes and smokers of regular cigarettes. Both total NNAL and total PAHs were significantly correlated with cotinine and trans-3′-hydroxycotinine (p<0.001 for all four correlations). Conclusions Our findings showed that herbal cigarettes did not deliver less carcinogens than regular cigarettes. The public needs to be aware of this fact and the Chinese tobacco industry should avoid misleading the public when promoting herbal cigarettes as safer products. PMID:19959701

  14. Reasons for quitting cigarette smoking and electronic cigarette use for cessation help

    PubMed Central

    Pokhrel, Pallav; Herzog, Thaddeus A.

    2015-01-01

    Despite the lack of clarity regarding their safety and efficacy as smoking cessation aids, electronic or e-cigarettes are commonly used to quit smoking. Currently little is understood about why smokers may use e-cigarettes for help with smoking cessation compared to other, proven cessation aids. This study aimed to determine the reasons for wanting to quit cigarettes that are associated with the use of e-cigarettes for cessation help versus the use of conventional Nicotine Replacement Therapy (NRT) products (e.g., gums). Cross-sectional, self-report data were obtained from multiethnic 1988 current daily smokers [M age = 45.1 (SD = 13.0); 51.3% Women] who had made an average lifetime quit attempts of 8.5 (SD = 18.7) but were not currently engaged in a cessation attempt. Reasons for wanting to quit smoking were assessed by using the Reasons for Quitting (RFQ) scale. Path analyses suggested that among reasons for quitting cigarettes, “immediate reinforcement,” a measure of wanting to quit cigarettes for extrinsic reasons such as bad smell, costliness and untidiness, was significantly associated with having tried e-cigarettes for cessation help, and “concerns about health” was associated with having tried NRT-only use. E-cigarettes appear to provide an alternative “smoking” experience to individuals who wish to quit cigarette smoking because of the immediate, undesirable consequences of tobacco smoking (e.g., smell, ash, litter) rather than concerns about health. Provided that the safety of e-cigarette use is ensured, e-cigarettes may be effectively used to reduce tobacco exposure among smokers who may not want to quit cigarettes for intrinsic motivation. PMID:25180551

  15. Evaluating nicotine dependence levels in e-cigarette users.

    PubMed

    González Roz, Alba; Secades Villa, Roberto; Weidberg, Sara

    2017-01-11

    Despite the fact that electronic cigarettes (e-cigarettes) are rapidly growing in popularity and use worldwide, there is scarce scientific data on abuse liability among e-cigarette users, and about whether e-cigarette use is related to nicotine dependence or not. The aim of this study is to explore nicotine dependence levels in a sample of experienced e-cigarette users (n= 39) and to compare them with current tobacco cigarette smokers (n=42). We conducted several face-to-face interviews in order to assess sociodemographic and dependence related characteristics in both e-cigarette users and in smokers. Adapted versions of both the Fagerström test for nicotine dependence (FTND) and the nicotine dependence syndrome scale (NDSS) were used to analyze nicotine dependence in each of the groups. Biochemical markers of carbon monoxide and urinary cotinine analysis were also collected. Results showed that e-cigarette users scored lower than cigarette smokers in both FTND and all NDSS subscales. Our findings extend previous research on e-cigarette use and nicotine addiction and suggest that e-cigarette users are less dependent on nicotine than current tobacco cigarette smokers. Further prospective studies are needed to better ascertain their addictiveness potential, comparing those smokers who switched to e-cigarettes from smoking cigarettes, and those who had never been tobacco cigarette smokers.

  16. Nicotine Replacement, Topography, and Smoking Phenotypes of E-cigarettes

    PubMed Central

    Strasser, Andrew A.; Souprountchouk, Valentina; Kaufmann, Amanda; Blazekovic, Sonja; Leone, Frank; Benowitz, Neal L.; Schnoll, Robert A.

    2016-01-01

    Objectives Little is known about the degree of nicotine replacement across first-generation e-cigarette brands, how e-cigarettes are used, and if there is variation across brands in relevant smoking phenotypes. The objective of this project was to collect data that are critical to better understanding, use, and exposure when using e-cigarettes, which may then inform clinical trials and tobacco regulatory policy. Methods Twenty-eight cigarette smokers were randomized to use one of 5 popular brands of e-cigarettes for a 10-day study. Day 1 (own cigarette brand) data established baseline levels for cotinine, carbon monoxide (CO), topography, cigarette liking, withdrawal, and craving. Participants returned on Days 5 and 10 to reassess these measures while exclusively using e-cigarettes. Results Compared to cigarette smoking, e-cigarettes provided significantly lower nicotine levels (25%-50%), reduced CO exposure, and lower ratings of liking (p < .05). Topography significantly differed between cigarette and e-cigarette sessions (p < .05). All brands significantly reduced withdrawal and craving (p < .05). There were no significant brand differences in outcome measures associated with exposure or use. Conclusions E-cigarettes are not liked as much as cigarettes, provide significantly lower nicotine replacement, reduce CO exposure, and mitigate withdrawal and craving. The patterns of use significantly differ compared to cigarette smoking. PMID:27942543

  17. [Cigarette prices, tobacco taxes and the proportion of contraband cigarettes in Germany].

    PubMed

    Effertz, T; Schlittgen, R

    2013-06-01

    Taxes on tobacco products are among the most efficient instruments against tobacco consumption and the arising cost of illness associated with them. The main argument of the tobacco industry against increases of excise taxes on cigarettes is a presumed substitution effect of smokers turning from consumption of legal cigarettes to smuggled ones. Besides deriving this proposition from the tobacco industry's own funded research, it has never been tested empirically. This article analyses the interdependence between contraband cigarettes and cigarette prices in Germany. Using VAR-modelling on the time-series of the variables of interest, we find no empirically valid correlation or causation between prices and untaxed contraband cigarettes. Furthermore, we find a positive relationship between contraband and legal taxed cigarettes, i. e., when the demand for legal cigarettes decreased in amount, so did the quantity of untaxed cigarettes. We conclude that the proposed relationship between prices and smuggled cigarettes as well as an overall substitution effect among smokers is non-existent. This has important implications for public health policy. The proposition that higher taxes on tobacco products incur social costs from increased smuggling activity cannot be corroborated empirically. Furthermore, this finding should encourage public health policy to keep using tobacco taxes as an instrument for prevention.

  18. Awareness of FDA-mandated cigarette packaging changes among smokers of 'light' cigarettes.

    PubMed

    Falcone, M; Bansal-Travers, M; Sanborn, P M; Tang, K Z; Strasser, A A

    2015-02-01

    Previous research has clearly demonstrated that smokers associate cigarette descriptors such as 'light', 'ultra-light' and 'low tar' with reduced health risks, despite evidence showing that cigarettes with these descriptor terms do not present lower health risk. In June 2010, regulations implemented by the US Food and Drug Administration went into effect to ban the use of 'light', 'mild' and 'low' on cigarette packaging. We surveyed smokers participating in human laboratory studies at our Center in Philadelphia, PA, USA shortly after the ban went into effect to determine the extent of awareness of recent cigarette packaging changes among smokers of light cigarettes. In our sample of 266 smokers, 76 reported smoking light cigarettes, but fewer than half of these smokers reported noticing changes to their cigarette packaging. Simple removal of a few misleading terms may be too subtle of a change to register with consumers of so-called 'low tar' cigarettes; more comprehensive regulation of cigarette packaging design may be necessary to gain smokers' attention and minimize misperceptions associated with tobacco pack design characteristics and color.

  19. Radiation Dose from Cigarette Tobacco

    NASA Astrophysics Data System (ADS)

    Papastefanou, C.

    2008-08-01

    The radioactivity in tobacco leaves collected from 15 different regions of Greece before cigarette production was studied in order to estimate the effective dose from cigarette tobacco due to the naturally occurring primordial radionuclides, such as 226Ra and 210Pb of the uranium series and 228Ra of the thorium series and/or man-made produced radionuclides, such as 137Cs of Chernobyl origin. Gamma-ray spectrometry was applied using Ge planar and coaxial type detectors of high resolution and high efficiency. It was concluded that the annual effective dose due to inhalation for adults (smokers) for 226Ra varied from 42.5 to 178.6 μSv y-1 (average 79.7 μSv y-1), while for 228Ra from 19.3 to 116.0 μSv y-1 (average 67.1 μSv y-1) and for 210Pb from 47.0 to 134.9 μSv y-1 (average 104.7 μSv y-1), that is the same order of magnitude for each radionuclide. The sum of the effective dose of the three natural radionuclides varied from 151.9 to 401.3 μSv y-1 (average 251.5 μSv y-1). The annual effective dose from 137Cs of Chernobyl origin was three orders of magnitude lower as it varied from 70.4 to 410.4 nSv y-1 (average 199.3 nSv y-1).

  20. Radiation dose from cigarette tobacco

    SciTech Connect

    Papastefanou, C.

    2008-08-07

    The radioactivity in tobacco leaves collected from 15 different regions of Greece before cigarette production was studied in order to estimate the effective dose from cigarette tobacco due to the naturally occurring primordial radionuclides, such as {sup 226}Ra and {sup 210}Pb of the uranium series and {sup 228}Ra of the thorium series and/or man-made produced radionuclides, such as {sup 137}Cs of Chernobyl origin. Gamma-ray spectrometry was applied using Ge planar and coaxial type detectors of high resolution and high efficiency. It was concluded that the annual effective dose due to inhalation for adults (smokers) for {sup 226}Ra varied from 42.5 to 178.6 {mu}Sv y{sup -1} (average 79.7 {mu}Sv y{sup -1}), while for {sup 228}Ra from 19.3 to 116.0 {mu}Sv y{sup -1} (average 67.1 {mu}Sv y{sup -1}) and for {sup 210}Pb from 47.0 to 134.9 {mu}Sv y{sup -1} (average 104.7 {mu}Sv y{sup -1}), that is the same order of magnitude for each radionuclide. The sum of the effective dose of the three natural radionuclides varied from 151.9 to 401.3 {mu}Sv y{sup -1} (average 251.5 {mu}Sv y{sup -1}). The annual effective dose from {sup 137}Cs of Chernobyl origin was three orders of magnitude lower as it varied from 70.4 to 410.4 nSv y{sup -1} (average 199.3 nSv y{sup -1})

  1. How hearing about harmful chemicals affects smokers' interest in dual use of cigarettes and e-cigarettes.

    PubMed

    Pepper, Jessica K; Byron, M Justin; Ribisl, Kurt M; Brewer, Noel T

    2017-03-01

    Substantial harm could result from concurrent cigarette and e-cigarette use (i.e., dual use) were it to undermine smoking cessation. Perceptions of chemical exposure and resulting harms may influence dual use. We conducted a probability-based phone survey of 1164 U.S. adult cigarette smokers in 2014-2015 and analyzed results in 2016. In a between-subjects experiment, smokers heard a hypothetical scenario in which cigarettes and e-cigarettes had the same amount of harmful chemicals or cigarettes had more chemicals than e-cigarettes (10× more, 100× more, or chemicals were present only in cigarettes). Smokers indicated how the scenario would change their interest in dual use and perceived health harms. Few smokers (7%) who heard that the products have the same amount of chemicals were interested in initiating or increasing dual use. However, more smokers were interested when told that cigarettes have 10× more chemicals than e-cigarettes (31%), 100× more chemicals than e-cigarettes (32%), or chemicals were present only in cigarettes (43%) (all p<.001). Individuals told that cigarettes have more chemicals were more likely than those in the "same amount" scenario to perceive that cigarettes would be more harmful than e-cigarettes (79% vs. 41%, OR=5.41, 95% CI=4.08-7.17). These harm perceptions partially explained the relationship between chemical scenario and dual use interest. Smokers associated higher chemical amounts in cigarettes versus e-cigarettes with greater health harms from cigarettes and thus expressed increased interest in dual use. The findings suggest that disclosing amounts of chemicals in cigarette smoke and e-cigarette aerosol could unintentionally encourage dual use.

  2. Cigarette smoke exposure exacerbates lung inflammation and compromises immunity to bacterial infection.

    PubMed

    Lugade, Amit A; Bogner, Paul N; Thatcher, Thomas H; Sime, Patricia J; Phipps, Richard P; Thanavala, Yasmin

    2014-06-01

    The detrimental impact of tobacco on human health is clearly recognized, and despite aggressive efforts to prevent smoking, close to one billion individuals worldwide continue to smoke. People with chronic obstructive pulmonary disease are susceptible to recurrent respiratory infections with pathogens, including nontypeable Haemophilus influenzae (NTHI), yet the reasons for this increased susceptibility are poorly understood. Because mortality rapidly increases with multiple exacerbations, development of protective immunity is critical to improving patient survival. Acute NTHI infection has been studied in the context of cigarette smoke exposure, but this is the first study, to our knowledge, to investigate chronic infection and the generation of adaptive immune responses to NTHI after chronic smoke exposure. After chronic NTHI infection, mice that had previously been exposed to cigarette smoke developed increased lung inflammation and compromised adaptive immunity relative to air-exposed controls. Importantly, NTHI-specific T cells from mice exposed to cigarette smoke produced lower levels of IFN-γ and IL-4, and B cells produced reduced levels of Abs against outer-membrane lipoprotein P6, with impaired IgG1, IgG2a, and IgA class switching. However, production of IL-17, which is associated with neutrophilic inflammation, was enhanced. Interestingly, cigarette smoke-exposed mice exhibited a similar defect in the generation of adaptive immunity after immunization with P6. Our study has conclusively demonstrated that cigarette smoke exposure has a profound suppressive effect on the generation of adaptive immune responses to NTHI and suggests the mechanism by which prior cigarette smoke exposure predisposes chronic obstructive pulmonary disease patients to recurrent infections, leading to exacerbations and contributing to mortality.

  3. Low-dose gamma-irradiation inhibits IL-6 secretion from human lung fibroblasts that promotes bronchial epithelial cell transformation by cigarette-smoke carcinogen.

    PubMed

    Chen, Wenshu; Xu, Xiuling; Bai, Lang; Padilla, Mabel T; Gott, Katherine M; Leng, Shuguang; Tellez, Carmen S; Wilder, Julie A; Belinsky, Steven A; Scott, Bobby R; Lin, Yong

    2012-07-01

    Despite decades of research in defining the health effects of low-dose (<100 mGy) ionizing photon radiation (LDR), the relationship between LDR and human cancer risk remains elusive. Because chemical carcinogens modify the tumor microenvironment, which is critical for cancer development, we investigated the role and mechanism of LDR in modulating the response of stromal cells to chemical carcinogen-induced lung cancer development. Secretion of proinflammatory cytokines such as interleukin-6 (IL-6), CXCL1 and CXCL5 from human lung fibroblasts was induced by cigarette-smoke carcinogen benzo[a]pyrene diol epoxide (BPDE), which was inhibited by a single dose of LDR. The activation of NF-κB, which is important for BPDE-induced IL-6 secretion, was also effectively suppressed by LDR. In addition, conditioned media from BPDE-treated fibroblasts activated STAT3 in the immortalized normal human bronchial epithelial cell line Beas-2B, which was blocked with an IL-6 neutralizing antibody. Conditioned medium from LDR-primed and BPDE-treated fibroblast showed diminished capacity in activating STAT3. Furthermore, IL-6 enhanced BPDE-induced Beas-2B cell transformation in vitro. These results suggest that LDR inhibits cigarette smoke-induced lung carcinogenesis by suppressing secretion of cytokines such as IL-6 from fibroblasts in lung tumor-prone microenvironment.

  4. Smoking behaviors and intentions among current e-cigarette users, cigarette smokers, and dual users: A national survey of U.S. high school seniors.

    PubMed

    McCabe, Sean Esteban; Veliz, Phil; McCabe, Vita V; Boyd, Carol J

    2017-03-01

    E-cigarette use among adolescents has increased significantly in recent years, but it remains unclear whether cigarette smoking behaviors and intentions for future cigarette smoking differ among current (i.e., 30-day) non-users, only e-cigarette users, only cigarette smokers, and dual users. A nationally representative sample of 4385 U.S. high school seniors were surveyed during the spring of their senior year via self-administered questionnaires in 2014. An estimated 9.6% of U.S. high school seniors reported current e-cigarette use only, 6.3% reported current cigarette smoking only, and 7.2% reported current dual use of e-cigarettes and cigarette smoking. There were no significant differences between current only cigarette smokers and dual users in the odds of early onset of cigarette smoking, daily cigarette smoking, intentions for future cigarette smoking, friends' cigarette smoking behaviors, attempts to quit cigarette smoking, or the inability to quit cigarette smoking. Adolescents who only used e-cigarettes had higher odds of intentions for future cigarette smoking in the next 5years (AOR=2.57, 95% CI: 1.21-5.24) than current non-users. Dual users and only cigarette smokers had higher odds of cigarette smoking behaviors and intentions for future cigarette smoking than non-users or only e-cigarette users. Adolescents who engage in current dual use have cigarette smoking behaviors and intentions for future cigarette smoking that more closely resemble cigarette smokers than e-cigarette users. Adolescents who only use e-cigarettes have higher intentions to engage in future cigarette smoking relative to their peers who do not engage in e-cigarette use or cigarette smoking.

  5. [Smoking and electronic cigarettes in France].

    PubMed

    Berlin, Ivan

    2016-12-01

    France is one of the developed countries where the prevalence of tobacco use is the highest. The reduction of incidence and prevalence of tobacco use in the near future would considerably decrease tobacco associated mortality and morbidity. The electronic cigarette, a consumer product that delivers pharmacologically active substances, is used by several millions of persons in France. The benefit-risk ratio of electronic cigarette use is unknown, as of today.

  6. Electronic cigarette solutions and resultant aerosol profiles.

    PubMed

    Herrington, Jason S; Myers, Colton

    2015-10-30

    Electronic cigarettes (e-cigarettes) are growing in popularity exponentially. Despite their ever-growing acceptance, their aerosol has not been fully characterized. The current study focused on evaluating e-cigarette solutions and their resultant aerosol for potential differences. A simple sampling device was developed to draw e-cigarette aerosol into a multi-sorbent thermal desorption (TD) tube, which was then thermally extracted and analyzed via a gas chromatography (GC) mass spectrometry (GC-MS) method. This novel application provided detectable levels of over one hundred fifteen volatile organic compounds (VOCs) and semivolatile organic compounds (SVOCs) from a single 40mL puff. The aerosol profiles from four commercially available e-cigarettes were compared to their respective solution profiles with the same GC-MS method. Solution profiles produced upwards of sixty four unidentified and identified (some only tentatively) constituents and aerosol profiles produced upwards of eighty two compounds. Results demonstrated distinct analyte profiles between liquid and aerosol samples. Most notably, formaldehyde, acetaldehyde, acrolein, and siloxanes were found in the aerosol profiles; however, these compounds were never present in the solutions. These results implicate the aerosolization process in the formation of compounds not found in solutions; have potential implications for human health; and stress the need for an emphasis on electronic cigarette aerosol testing.

  7. E-cigarettes: a rapidly growing Internet phenomenon.

    PubMed

    Yamin, Cyrus K; Bitton, Asaf; Bates, David W

    2010-11-02

    Electronic cigarettes (e-cigarettes) aerosolize nicotine and produce a vapor that emulates that of cigarettes but purportedly has fewer traditional toxins than secondhand smoke. Although e-cigarettes are widely sold online and by retailers, new research suggests that they may contain unexpected toxins and may provide unreliable nicotine delivery. Many countries have already banned or strictly regulated e-cigarettes. Currently in the United States, e-cigarettes are exempt from regulation as drug-delivery devices. Meanwhile, the presence of e-cigarettes on the Internet, including in Web searches, virtual user communities, and online stores where people sell e-cigarettes on commission, is increasing rapidly. Physicians should be aware of the popularity, questionable efficacy claims, and safety concerns of e-cigarettes so that they may counsel patients against use and advocate for research to inform an evidence-based regulatory approach.

  8. Public health challenges of electronic cigarettes in South Korea.

    PubMed

    Lee, Sungkyu; Kimm, Heejin; Yun, Ji Eun; Jee, Sun Ha

    2011-11-01

    Electronic cigarettes (e-cigarrettes) were recently introduced and advertised as a smoking cession device in South Korea. As the social norm to quit smoking has gained hold in the country, the number of e-cigarette users is growing rapidly. This phenomenon should be urgently considered, because of the lack of research that has been conducted to examine the safety of e-cigarettes and its efficacy as a smoking cessation aid. This paper raises several public health concerns on e-cigarettes in South Korea. Uncertain regulations of the government on e-cigarettes are contributing to an increase of e-cigarette users and allowing the e-cigarette industry to circumvent existing regulations. The aggressive marketing activity of this industry is also a core factor that is responsible for the rapid increase of e-cigarette use, in particular among the youth. Following the enforcement of tobacco control, some cigarette smokers may be encouraged to purchase e-cigarettes in order to circumvent the regulations, even though the dual use of e-cigarette and cigarette may be more harmful. Until there is clear evidence of the e-cigarette's safety, it is recommended that the industry's marketing and promotional activities be banned and closely monitored, and public campaigns be initiated to educate the public regarding e-cigarettes.

  9. Corneoscleral Laceration and Ocular Burns Caused by Electronic Cigarette Explosions

    PubMed Central

    Paley, Grace L.; Echalier, Elizabeth; Eck, Thomas W.; Hong, Augustine R.; Gregory, Darren G.; Lubniewski, Anthony J.

    2016-01-01

    Purpose: To report cases of acute globe rupture and bilateral corneal burns from electronic cigarette (EC) explosions. Methods: Case series. Results: We describe a series of patients with corneal injury caused by EC explosions. Both patients suffered bilateral corneal burns and decreased visual acuity, and one patient sustained a unilateral corneoscleral laceration with prolapsed iris tissue and hyphema. A review of the scientific literature revealed no prior reported cases of ocular injury secondary to EC explosions; however, multiple media and government agency articles describe fires and explosions involving ECs, including at least 4 with ocular injuries. Conclusions: Given these cases and the number of recent media reports, ECs pose a significant public health risk. Users should be warned regarding the possibility of severe injury, including sight-threatening ocular injuries ranging from corneal burns to full-thickness corneoscleral laceration. PMID:27191672

  10. 78 FR 52679 - Safety Standard for Cigarette Lighters; Adjusted Customs Value for Cigarette Lighters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... 1210 Safety Standard for Cigarette Lighters; Adjusted Customs Value for Cigarette Lighters AGENCY: Consumer Product Safety Commission. ACTION: Final rule. SUMMARY: The Commission has a safety standard... standard defines ``disposable lighters,'' in part, as refillable lighters that use butane or similar...

  11. Awareness of FDA-Mandated Cigarette Packaging Changes among Smokers of "Light" Cigarettes

    ERIC Educational Resources Information Center

    Falcone, M.; Bansal-Travers, M.; Sanborn, P. M.; Tang, K. Z.; Strasser, A. A.

    2015-01-01

    Previous research has clearly demonstrated that smokers associate cigarette descriptors such as "light", "ultra-light" and "low tar" with reduced health risks, despite evidence showing that cigarettes with these descriptor terms do not present lower health risk. In June 2010, regulations implemented by the US Food and…

  12. Social Influences on Use of Cigarettes, E-Cigarettes, and Hookah by College Students

    ERIC Educational Resources Information Center

    Noland, Melody; Ickes, Melinda J.; Rayens, Mary Kay; Butler, Karen; Wiggins, Amanda T.; Hahn, Ellen J.

    2016-01-01

    Objectives: (1) Compare social norms and perceived peer use between college student cigarette, e-cigarette, and/or hookah users and nonusers; and (2) determine variables associated with social influences. Participants: Undergraduate students attending a large university in the Southeast United States (N = 511). Methods: An April 2013 online survey…

  13. E-cigarette specialty retailers: Data to assess the association between retail environment and student e-cigarette use.

    PubMed

    Bostean, Georgiana; Crespi, Catherine M; Vorapharuek, Patsornkarn; McCarthy, William J

    2017-04-01

    The retail environment is a major social determinant of health, yet little is known about the e-cigarette specialty retailer environment. The e-cigarette specialty retail environment may be associated with e-cigarette use by middle and high school students, an issue that was addressed in a recent article entitled, "E-cigarette use among students and e-cigarette specialty retailer presence near schools," by Bostean and colleagues (G. Bostean, C.M. Crespi, P. Vorapharuek, W.J. McCarthy, 2016 [1]). We present data relating to e-cigarette specialty retailers in Orange County, California. We describe the data collection method (including the search methodology to identify e-cigarette specialty retailers), present descriptive retailer data including school proximity, and provide data from multi-level regressions predicting individual-level student use of e-cigarettes based on presence of an e-cigarette specialty retailer in proximity to schools.

  14. Smoking induces epithelial-to-mesenchymal transition in non-small cell lung cancer through HDAC-mediated downregulation of E-cadherin.

    PubMed

    Nagathihalli, Nagaraj S; Massion, Pierre P; Gonzalez, Adriana L; Lu, Pengcheng; Datta, Pran K

    2012-11-01

    Epidemiological studies have shown that most cases of lung cancers (85%-90%) are directly attributable to tobacco smoking. Although association between cigarette smoking and lung cancer is well documented, surprisingly little is known about the molecular mechanisms of how smoking is involved in epithelial-to-mesenchymal transition (EMT) through epigenetic changes. Here, we show that lung cancer patients with a smoking history have low E-cadherin levels and loss of E-cadherin is a poor prognostic factor in smokers. Moreover, the downregulation of E-cadherin correlates with the number of pack years. In an attempt to determine the role of long-term cigarette smoking on EMT, we observed that treatment of lung cell lines with cigarette smoke condensate (CSC) induces EMT through downregulation of epithelial markers, including E-cadherin and upregulation of mesenchymal markers. CSC decreases E-cadherin expression at the transcriptional level through upregulation of LEF1 and Slug, and knockdown of these two proteins increases E-cadherin expression. Importantly, chromatin immunoprecipitation assays suggest that LEF-1 and Slug binding to E-cadherin promoter is important for CSC-mediated downregulation of E-cadherin. The histone deacetylase (HDAC) inhibitor MS-275 reverses CSC-induced EMT, migration, and invasion through the restoration of E-cadherin expression. These results suggest that recruitment of HDACs by transcriptional repressors LEF-1 and Slug is responsible for E-cadherin suppression and EMT in cigarette smokers and provide a potential drug target toward the treatment of lung cancer.

  15. Impaired Transcriptional Response of the Murine Heart to Cigarette Smoke in the Setting of High Fat Diet and Obesity

    SciTech Connect

    Tilton, Susan C.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Mikheev, Vladimir B.; Lee, K. M.; Corley, Richard A.; Pounds, Joel G.; Bigelow, Diana J.

    2013-07-01

    Smoking and obesity are each well-established risk factors for cardiovascular heart disease, which together impose earlier onset and greater severity of disease. To identify early signaling events in the response of the heart to cigarette smoke exposure within the setting of obesity, we exposed normal weight and high fat diet-induced obese (DIO) C57BL/6 mice to repeated inhaled doses of mainstream (MS) or sidestream (SS) cigarette smoke administered over a two week period, monitoring effects on both cardiac and pulmonary transcriptomes. MS smoke (250 μg wet total particulate matter (WTPM)/L, 5 h/day) exposures elicited robust cellular and molecular inflammatory responses in the lung with 1466 differentially expressed pulmonary genes (p < 0.01) in normal weight animals and a much-attenuated response (463 genes) in the hearts of the same animals. In contrast, exposures to SS smoke (85 μg WTPM/L) with a CO concentration equivalent to that of MS smoke (250 CO ppm) induced a weak pulmonary response (328 genes) but an extensive cardiac response (1590 genes). SS smoke and to a lesser extent MS smoke preferentially elicited hypoxia- and stress-responsive genes as well as genes predicting early changes of vascular smooth muscle and endothelium, precursors of cardiovascular disease. The most sensitive smoke-induced cardiac transcriptional changes of normal weight mice were largely absent in DIO mice after smoke exposure, while genes involved in fatty acid utilization were unaffected. At the same time, smoke exposure suppressed multiple proteome maintenance genes induced in the hearts of DIO mice. Together, these results underscore the sensitivity of the heart to SS smoke and reveal adaptive responses in healthy individuals that are absent in the setting of high fat diet and obesity.

  16. Comparison of Biological Responses in Rats Under Various Cigarette Smoke Exposure Conditions

    PubMed Central

    Tsuji, Hiroyuki; Fujimoto, Hitoshi; Matsuura, Daiki; Nishino, Tomoki; Lee, K Monica; Yoshimura, Hiroyuki

    2013-01-01

    A variety of exposure regimens of cigarette smoke have been used in animal models of lung diseases. In this study, we compared biological responses of smoke exposure in rats, using different smoke concentrations (wet total particulate matter [WTPM]), daily exposure durations, and total days of exposure. As a range-finding acute study, we first compared pulmonary responses between SD and F344 strains after a single nose-only exposure to mainstream cigarette smoke or LPS. Secondly, F344 rats were exposed to cigarette smoke for 2 or 13 weeks under the comparable daily exposure dose (WTPM concentration x daily exposure duration; according to Haber’s rule) but at a different WTPM concentration or daily exposure duration. Blood carboxylhemoglobin was increased linearly to the WTPM concentration, while urinary nicotine plus cotinine value was higher for the longer daily exposure than the corresponding shorter exposure groups. Gamma glutamyl transferase activity in bronchoalveolar lavage fluid (BALF) was increased dose dependently after 2 and 13 weeks of cigarette smoke exposure, while the neutrophil content in BALF was not increased notably. Smoke-exposed groups showed reduced body weight gain and increased relative lung and heart weights. While BALF parameters and the relative lung weights suggest pulmonary responses, histopathological examination showed epithelial lesions mainly in the upper respiratory organs (nose and larynx). Collectively, the results indicate that, under the employed study design, the equivalent daily exposure dose (exposure concentration x duration) induces equivalent pulmonary responses in rats. PMID:23914058

  17. Use of the Zebrafish Larvae as a Model to Study Cigarette Smoke Condensate Toxicity

    PubMed Central

    Ellis, Lee D.; Soo, Evelyn C.; Achenbach, John C.; Morash, Michael G.; Soanes, Kelly H.

    2014-01-01

    The smoking of tobacco continues to be the leading cause of premature death worldwide and is linked to the development of a number of serious illnesses including heart disease, respiratory diseases, stroke and cancer. Currently, cell line based toxicity assays are typically used to gain information on the general toxicity of cigarettes and other tobacco products. However, they provide little information regarding the complex disease-related changes that have been linked to smoking. The ethical concerns and high cost associated with mammalian studies have limited their widespread use for in vivo toxicological studies of tobacco. The zebrafish has emerged as a low-cost, high-throughput, in vivo model in the study of toxicology. In this study, smoke condensates from 2 reference cigarettes and 6 Canadian brands of cigarettes with different design features were assessed for acute, developmental, cardiac, and behavioural toxicity (neurotoxicity) in zebrafish larvae. By making use of this multifaceted approach we have developed an in vivo model with which to compare the toxicity profiles of smoke condensates from cigarettes with different design features. This model system may provide insights into the development of smoking related disease and could provide a cost-effective, high-throughput platform for the future evaluation of tobacco products. PMID:25526262

  18. Attitudes toward E-Cigarettes, Reasons for Initiating E-Cigarette Use, and Changes in Smoking Behavior after Initiation: A Pilot Longitudinal Study of Regular Cigarette Smokers

    PubMed Central

    Barr, Dana Boyd; Stratton, Erin; Escoffery, Cam; Kegler, Michelle

    2015-01-01

    Objectives We examined 1) changes in smoking and vaping behavior and associated cotinine levels and health status among regular smokers who were first-time e-cigarette purchasers and 2) attitudes, intentions, and restrictions regarding e-cigarettes. Methods We conducted a pilot longitudinal study with assessments of the aforementioned factors and salivary cotinine at weeks 0, 4, and 8. Eligibility criteria included being ≥18 years old, smoking ≥25 of the last 30 days, smoking ≥5 cigarettes per day (cpd), smoking regularly ≥1 year, and not having started using e-cigarettes. Of 72 individuals screened, 40 consented, 36 completed the baseline survey, and 83.3% and 72.2% were retained at weeks 4 and 8, respectively. Results Participants reduced cigarette consumption from baseline to week 4 and 8 (p’s < 0.001); 23.1% reported no cigarette use in the past month at week 8. There was no significant decrease in cotinine from baseline to week 4 or 8 (p’s = ns). At week 8, the majority reported improved health (65.4%), reduced smoker’s cough (57.7%), and improved sense of smell (53.8%) and taste (50.0%). The majority believed that e-cigarettes versus regular cigarettes have fewer health risks (97.2%) and that e-cigarettes have been shown to help smokers quit (80.6%) and reduce cigarette consumption (97.2%). In addition, the majority intended to use e-cigarettes as a complete replacement for regular cigarettes (69.4%) and reported no restriction on e-cigarette use in the home (63.9%) or car (80.6%). Conclusions Future research is needed to document the long-term impact on smoking behavior and health among cigarette smokers who initiate use of e-cigarettes. PMID:25621193

  19. Does the availability of single cigarettes promote or inhibit cigarette consumption? Perceptions, prevalence and correlates of single cigarette use among adult Mexican smokers

    PubMed Central

    Thrasher, J F; Villalobos, V; Dorantes-Alonso, A; Arillo-Santillán, E; Cummings, K Michael; O’Connor, R; Fong, G T

    2009-01-01

    Background: Single cigarette use and its implications have rarely been studied among adults. Objective: To assess perceptions, prevalence and correlates of single cigarette purchase behaviour and its relation to harm reduction. Design: Focus group transcripts and cross-sectional data were analysed. Setting and participants: Focus groups among convenience samples of adult smokers in two Mexican cities and a population-based sample of 1079 adult smokers from the International Tobacco Control Policy Evaluation Project in four Mexican cities. Main outcome measures: Purchase of single cigarettes last time cigarettes were bought, frequency of purchasing single cigarettes in the previous month and intention to quit in the next 6 months. Results: Focus group data indicated that smokers bought single cigarettes as a harm reduction strategy. Survey data indicated that 38% of participants purchased single cigarettes in the last month and 10% purchased them the last time they bought cigarettes, with more frequent consumption among young adults and those with lower income. Purchasing single cigarettes was independently associated with the frequency of using single cigarettes to reduce consumption and, less consistently, with the frequency of being cued to smoke after seeing single cigarettes for sale. Using single cigarettes to reduce consumption was positively associated with quit intention, whereas being cued to smoke by single cigarettes was negatively associated with quit intention. Conclusions: Study results suggest that some adult Mexican smokers purchase single cigarettes as a method to limit, cut down on and even quit smoking. Nevertheless, promotion of the availability of single cigarettes as a harm reduction strategy could provide additional smoking cues that undermine quit attempts and promote youth smoking. PMID:19671535

  20. Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner

    PubMed Central

    Daijo, Hiroki; Hoshino, Yuma; Kai, Shinichi; Suzuki, Kengo; Nishi, Kenichiro; Matsuo, Yoshiyuki; Harada, Hiroshi; Hirota, Kiichi

    2016-01-01

    Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF-1α protein in human lung epithelial-like cells under non-hypoxic conditions. Genes upregulated by HIF-1, including vascular endothelial growth factor and regulated in development and DNA damage response 1, both of which are involved in smoking-induced emphysematous changes, were increased by CSE treatment under non-hypoxic conditions in vitro and in vivo. Further investigation revealed that reactive oxygen species were generated in cells exposed to CSE and were required for CSE-mediated induction of HIF-1α protein, as was activation of phosphoinositide 3-kinase and mitogen-activated protein kinase pathways. In conclusion, we demonstrated that CSE and CS induced HIF-1 activation in vitro and in vivo, respectively. The evidence warrants further investigation to indicate that HIF-1 plays an important role in CS-induced gene expression, which is deeply involved in pulmonary cellular stress and small airway remodelling. PMID:27680676

  1. Smoker reactions to a "radio message" that Light cigarettes are as dangerous as Regular cigarettes.

    PubMed

    Kozlowski, L T; Goldberg, M E; Sweeney, C T; Palmer, R F; Pillitteri, J L; Yost, B A; White, E L; Stine, M M

    1999-03-01

    The purpose of this study was to examine in a systematic, controlled fashion the reactions of smokers to scientifically correct information about the risks of smoking Light cigarettes (about 6-15 mg tar by the FTC method). Random-digit dialing, computer-assisted telephone interviews were used to locate daily smokers of Light cigarettes. In an experimental design, smokers were randomly assigned to listen (n = 293) or not (n = 275) to a persuasive simulated radio message on the risks of Light cigarettes; 108 of those who did not listen to the message in the first part of the interview were played the message in the second part, to evaluate some repeated-measures effects. Those who heard the message were more likely to report that one Light cigarette could give a smoker the same amount of tar as one Regular cigarette and that Light cigarettes were more dangerous: 55% said the message made them think more about quitting and 46% said the message increased the amount they wanted to quit; 42% said that after hearing the message they thought Light cigarettes were more dangerous. Using the Theory of Planned Behavior, structural equation modeling analysis indicated that the message acted to increase intention to quit smoking by increasing the desire to quit smoking. Seventy-three per cent of the smokers agreed that it was important to play such messages widely on the radio; 77% agreed that there should be a warning on packs that vent blocking increases tar; 61% agreed that the location of filter vents should be marked. The majority of smokers of Light cigarettes seem to value being informed that Light cigarettes are as dangerous for them as Regular cigarettes, and this information increases their intentions to quit smoking.

  2. Does environmental cigarette smoke affect breastfeeding behavior?

    PubMed Central

    Firouzbakht, Mozhgan; Hajian-Tilaki, Karimallah; Nikpour, Maryam; Banihosseini, Zahra

    2017-01-01

    BACKGROUND: Exposure of lactating women to environmental cigarette smoke may increase cotinine in breast milk, which in turn may reduce the volume of milk and the duration of breastfeeding. OBJECTIVES: To assess the relationship between exposure to environmental cigarette smoke and breastfeeding behavior. MATERIALS AND METHODS: This prospective cohort study was conducted on 290 mothers in Babol - Iran, who had been breastfeeding for 3–5 days after delivery. The lactating mothers were divided into two groups: those exposed to environmental cigarette smoke, and those free from smoke exposure. The study questionnaire included demographic data, information on environmental cigarette smoke, and breastfeeding behavior. Data was collected through telephone interviews at 2, 4, and 6 months of follow-up. Statistical analysis included descriptive statistics, and test of significance using Chi-square test, t-test, log-rank test, and Cox proportional hazards model. RESULTS: The continuation of breastfeeding for the group of exposed mothers and the unexposed group was (mean ± standard deviation) 5.57 ± 0.098 and 5.58 ± 0.109, respectively in 6 months of follow-up. There was no significant difference between the two groups (P = 0.93). The percentage of exclusive breastfeeding at 6 months in the group exposed to cigarette smoke was 65% compared to 76% of the nonexposed group. However, the difference was not statistically significant (P = 0.149). CONCLUSIONS: In this study, no significant association was observed between the group exposed to environmental cigarette smoke and the nonexposed group in breastfeeding behavior, although the percentage of exclusive breastfeeding at 6 months was less in the group exposed to environmental cigarette smoke. Further exploratory studies are needed. PMID:28163575

  3. The Relation between Frequency of E-Cigarette Use and Frequency and Intensity of Cigarette Smoking among South Korean Adolescents

    PubMed Central

    Lee, Jung Ah; Lee, Sungkyu; Cho, Hong-Jun

    2017-01-01

    Introduction: The prevalence of adolescent electronic cigarette (e-cigarette) use has increased in most countries. This study aims to determine the relation between the frequency of e-cigarette use and the frequency and intensity of cigarette smoking. Additionally, the study evaluates the association between the reasons for e-cigarette use and the frequency of its use. Materials and Methods: Using the 2015 Korean Youth Risk Behavior Web-Based Survey, we included 6655 adolescents with an experience of e-cigarette use who were middle and high school students aged 13–18 years. We compared smoking experience, the frequency and intensity of cigarette smoking, and the relation between the reasons for e-cigarette uses and the frequency of e-cigarette use. Results: The prevalence of e-cigarette ever and current (past 30 days) users were 10.1% and 3.9%, respectively. Of the ever users, approximately 60% used e-cigarettes not within 1 month. On the other hand, 8.1% used e-cigarettes daily. The frequent and intensive cigarette smoking was associated with frequent e-cigarette uses. The percentage of frequent e-cigarette users (≥10 days/month) was 3.5% in adolescents who did not smoke within a month, but 28.7% among daily smokers. Additionally, it was 9.1% in smokers who smoked less than 1 cigarette/month, but 55.1% in smokers who smoked ≥20 cigarettes/day. The most common reason for e-cigarette use was curiosity (22.9%), followed by the belief that they are less harmful than conventional cigarettes (18.9%), the desire to quit smoking (13.1%), and the capacity for indoor use (10.7%). Curiosity was the most common reason among less frequent e-cigarette users; however, the desire to quit smoking and the capacity for indoor use were the most common reasons among more frequent users. Conclusions: Results showed a positive relation between frequency or intensity of conventional cigarette smoking and the frequency of e-cigarette use among Korean adolescents, and frequency of e-cigarette

  4. Psychiatric comorbidity in adolescent electronic and conventional cigarette use.

    PubMed

    Leventhal, Adam M; Strong, David R; Sussman, Steve; Kirkpatrick, Matthew G; Unger, Jennifer B; Barrington-Trimis, Jessica L; Audrain-McGovern, Janet

    2016-02-01

    The popularity of electronic (e-) cigarettes has greatly increased recently, particularly in adolescents. However, the extent of psychiatric comorbidity with adolescent e-cigarette use and dual use of conventional (combustible) and e-cigarettes is unknown. This study characterized psychiatric comorbidity in adolescent conventional and e-cigarette use. Ninth grade students attending high schools in Los Angeles, CA (M age = 14) completed self-report measures of conventional/e-cigarette use, emotional disorders, substance use/problems, and transdiagnostic psychiatric phenotypes consistent with the NIMH-Research Domain Criteria Initiative. Outcomes were compared by lifetime use of: (1) neither conventional nor e-cigarettes (non-use; N = 2557, 77.3%); (2) e-cigarettes only (N = 412, 12.4%); (3) conventional cigarettes only (N = 152, 4.6%); and (4) conventional and e-cigarettes (dual use; N = 189, 5.6%). In comparison to adolescents who used conventional cigarettes only, e-cigarette only users reported lower levels of internalizing syndromes (depression, generalized anxiety, panic, social phobia, and obsessive-compulsive disorder) and transdiagnostic phenotypes (i.e., distress intolerance, anxiety sensitivity, rash action during negative affect). Depression, panic disorder, and anhedonia were higher in e-cigarette only vs. non-users. For several externalizing outcomes (mania, rash action during positive affect, alcohol drug use/abuse) and anhedonia, an ordered pattern was observed, whereby comorbidity was lowest in non-users, moderate in single product users (conventional or e-cigarette), and highest in dual users. These findings: (1) raise question of whether emotionally-healthier ('lower-risk') adolescents who are not interested in conventional cigarettes are being attracted to e-cigarettes; (2) indicate that research, intervention, and policy dedicated to adolescent tobacco-psychiatric comorbidity should distinguish conventional cigarette, e-cigarette, and dual use.

  5. Perceptions of Secondhand E-Cigarette Aerosol Among Twitter Users

    PubMed Central

    Unger, Jennifer B.; Escobedo, Patricia; Allem, Jon-Patrick; Soto, Daniel W.; Chu, Kar-Hai; Cruz, Tess

    2016-01-01

    Objectives There is considerable debate among the public health community about the health risks of secondhand exposure to the aerosol from electronic cigarettes (e-cigarettes). Despite mounting scientific evidence on the chemical content of e-cigarette aerosol, public perceptions of the relative safety of secondhand e-cigarette aerosol have not been well characterized. Method This study collected tweets, or messages sent using Twitter, about exposure to secondhand e-cigarette aerosol over a 6-week period in 2015. Tweets were coded on sentiment about e-cigarettes (pro-, anti-, or neutral/unknown) and topic (health, social, advertisement, or unknown). Results The 1519 tweets included 531 pro-e-cigarette tweets, 392 anti-e-cigarette tweets, and 596 neutral tweets. Social tweets far outnumbered health tweets (747 vs. 182, respectively). Social-focused tweets were predominantly pro-e-cigarette, whereas health-focused tweets were predominantly anti-e-cigarette. Discussion Twitter discussions about secondhand vaping are dominated by pro-e-cigarette social tweets, although there is a presence of anti-e-cigarette social tweets and tweets about negative and positive health effects. Public health and regulatory agencies could use social media and traditional media to disseminate the message that e-cigarette aerosol contains potentially harmful chemicals and could be perceived as offensive. This study identifies the prevalent topics and opinions that could be incorporated into health education messages. PMID:28090560

  6. Cigarette smoking following a prolonged mental task exaggerates vasoconstriction in glabrous skin in habitual smokers.

    PubMed

    Uehara, Kouhei; Sone, Ryoko; Yamazaki, Fumio

    2010-12-01

    In the present study, to test the hypothesis that cigarette smoking and physical exercise induce different influences on peripheral vasomotor control after mental stress, we examined the physiological responses, including skin vasomotor responses, to smoking and exercise in six healthy smokers. The smokers performed 2 hr of mental arithmetic tasks (MT) followed by smoking or bicycle exercise (108 +/- 7W) for 10 min or a time control (i.e., rest without smoking) under thermally comfortable conditions (25 degrees C). Skin blood flow (laser-Doppler flowmetry) was monitored at glabrous (palm) and nonglabrous (forearm, forehead) sites. Cutaneous vascular conductance (CVC) was evaluated from the ratio of blood flow to mean arterial pressure (MAP). The prolonged MT increased MAP from 77.7 +/- 2.7 mmHg to 86.0 +/- 3.0 mmHg and reduced CVC in the palm by 27.4 +/- 5.6%, but did not change those in the forearm and forehead. Smoking after MT further decreased CVC in the palm, and the smoking-induced reduction in CVC persisted until 20 min after smoking. Meanwhile, CVC in the forearm and forehead transiently and minimally decreased during smoking. Exercise after MT increased CVC at the three sites, and the exercise-induced elevation of CVC in the palm persisted until 30 min after exercise. In the time control experiments, each variable remained unchanged throughout the recovery period of MT. It was suggested that smoking causes additional vasoconstriction in glabrous skin after prolonged MT, while the exercise-associated vasodilator effect counteracts the vasoconstrictor action of MT. We speculate that long-term mental stress and smoking behavior may synergistically develop chronic stress-induced vascular dysfunction, and the stress-related disorders may be reduced by habitual enforcement of moderate exercise.

  7. DNA methylation alterations in response to prenatal exposure of maternal cigarette smoking: A persistent epigenetic impact on health from maternal lifestyle?

    PubMed

    Nielsen, Christina H; Larsen, Agnete; Nielsen, Anders L

    2016-02-01

    Despite increased awareness, maternal cigarette smoking during pregnancy continues to be a common habit causing risk for numerous documented negative health consequences in the exposed children. It has been proposed that epigenetic mechanisms constitute the link between prenatal exposure to maternal cigarette smoking (PEMCS) and the diverse pathologies arising in later life. We here review the current literature, focusing on DNA methylation. Alterations in the global DNA methylation patterns were observed after exposure to maternal smoking during pregnancy in placenta, cord blood and buccal epithelium tissue. Further, a number of specific genes exemplified by CYP1A1, AhRR, FOXP3, TSLP, IGF2, AXL, PTPRO, C11orf52, FRMD4A and BDNF are shown to have altered DNA methylation patterns in at least one of these tissue types due to PEMCS. Investigations showing persistence and indications of trans-generational inheritance of DNA methylation alterations induced by smoking exposure are also described. Further, smoking-induced epigenetic manifestations can be both tissue-dependent and gender-specific which show the importance of addressing the relevant sex, tissue and cell types in the future studies linking specific epigenetic alterations to disease development. Moreover, the effect of paternal cigarette smoking and second-hand smoke exposure is documented and accordingly not to be neglected in future investigations and data evaluations. We also outline possible directions for the future research to address how DNA methylation alterations induced by maternal lifestyle, exemplified by smoking, have direct consequences for fetal development and later in life health and behavior of the child.

  8. Risk Factors for Exclusive E-Cigarette Use and Dual E-Cigarette Use and Tobacco Use in Adolescents

    PubMed Central

    Knight, Rebecca; Williams, Rebecca J.; Pagano, Ian; Sargent, James D.

    2015-01-01

    OBJECTIVE: To describe electronic cigarette (e-cigarette) use and cigarette use among adolescents and determine whether established risk factors for smoking discriminate user categories. METHODS: School-based survey of 1941 high school students (mean age 14.6 years) in Hawaii; data collected in 2013. The survey assessed e-cigarette use and cigarette use, alcohol and marijuana use, and psychosocial risk and protective variables (eg, parental support, academic involvement, smoking expectancies, peer smoking, sensation seeking). Analysis of variance and multinomial regression examined variation in risk and protective variables across the following categories of ever-use: e-cigarette only, cigarette only, dual use (use of both products), and nonuser (never used either product). RESULTS: Prevalence for the categories was 17% (e-cigarettes only), 12% (dual use), 3% (cigarettes only), and 68% (nonusers). Dual users and cigarette-only users were highest on risk status (elevated on risk factors and lower on protective factors) compared with other groups. E-cigarette only users were higher on risk status than nonusers but lower than dual users. E-cigarette only users and dual users more often perceived e-cigarettes as healthier than cigarettes compared with nonusers. CONCLUSIONS: This study reports a US adolescent sample with one of the largest prevalence rates of e-cigarette only use in the existing literature. Dual use also had a substantial prevalence. The fact that e-cigarette only users were intermediate in risk status between nonusers and dual users raises the possibility that e-cigarettes are recruiting medium-risk adolescents, who otherwise would be less susceptible to tobacco product use. PMID:25511118

  9. Development of a commercial cigarette "market map" comparison methodology for evaluating new or non-conventional cigarettes.

    PubMed

    Counts, M E; Hsu, F S; Tewes, F J

    2006-12-01

    A "market map" comparison methodology for cigarette smoke chemistry yields is presented. Federal Trade Commission machine-method smoke chemistry was determined for a range of filtered cigarettes from the US marketplace. These data were used to develop illustrative market maps for each smoke constituent as analytical tools for comparing new or non-conventional cigarettes to a sampling of the broader range of marketplace cigarettes. Each market map contained best-estimate "market-means," showing the relationship between commercial cigarette constituent and tar yields, and yield "market ranges" defined by prediction intervals. These market map means and ranges are the basis for comparing new cigarette smoke yields to those of conventional cigarettes. The potential utility of market maps for evaluating differences in smoke chemistry was demonstrated with 1R4F and 2R4F Kentucky reference cigarettes, an Accord cigarette, and an Advance cigarette. Conventional cigarette tobacco nicotine, nitrate, soluble ammonia, and tobacco specific nitrosamine levels are reported. Differences among conventional cigarette constituent yields at similar tar levels were explained in part by the chemical composition range of those cigarette tobaccos. The study also included a comparison of smoke constituent yields and in vitro smoke cytotoxicity and mutagenicity assay results for the 1R4F Kentucky reference cigarette and its replacement 2R4F. Significant smoke yield differences were noted for lead, NNK, and NNN. The majority of their smoke constituent yields were within the market range developed from the sampled conventional cigarettes. Within the sensitivity and specificity of the in vitro bioassays used, smoke toxic activity differences for the two reference cigarettes were not statistically significant. These results add to the limited information available for the 2R4F reference cigarette.

  10. Cigarette smoking and leukocyte subpopulations in men.

    PubMed

    Freedman, D S; Flanders, W D; Barboriak, J J; Malarcher, A M; Gates, L

    1996-07-01

    Because of previously reported associations among the total leukocyte count, cigarette smoking, and risk of cardiovascular disease, we examined the relation of cigarette smoking to various leukocyte subpopulations among 3467 men aged 31 to 45 years. The median total leukocyte count was 36% higher (7840 vs. 5760 cells/mL) among current cigarette smokers than among men who had never smoked, and both stratification and regression analyses were used to examine independent associations with leukocyte subpopulations. At equivalent counts of other subpopulations, CD4+ lymphocytes and neutrophils were the cell types most strongly associated with cigarette smoking; each standard deviation change in counts of these subpopulations increased the odds of current (vs. never) smoking by approximately threefold. Furthermore, whereas 15% of the 238 men with relatively low (< 25 percentile) counts of both neutrophils and CD4+ lymphocytes were cigarette smokers, 96% of the 249 men with relatively high counts of both subpopulations were current smokers. Counts of T lymphocytes also tended to be higher among the 32 men with self-reported ischemic heart disease than among other men. These results, along with previous reports of immunologically active T lymphocytes in atherosclerotic plaques, suggest that this subpopulation may be of particular interest in studies examining the relation of leukocytes to cardiovascular disease.

  11. Achieving appropriate regulations for electronic cigarettes

    PubMed Central

    Saitta, Daniela; Ferro, Giancarlo Antonio

    2014-01-01

    A growing body of scientific studies show that e-cigarettes may serve as an acceptable substitute for smoking tobacco cigarettes, thereby reducing or eliminating exposure to harmful elements in smoke. The success of e-cigarettes is such that sales of these products are rapidly gaining on traditional cigarettes. The rapidly evolving phenomenon is raising concerns for the health community, pharmaceutical industry, health regulators and state governments. Obviously, these products need to be adequately regulated, primarily to protect users. Depending on the form and intended scope, certain regulatory decisions may have diverse unintended consequences on public health and may face many different challenges. Ideally, before any regulations are enacted, the regulatory body will require sufficient scientific research to verify that a problem does exist, quantify the problem, explore all potential solutions including making no change at all, determine the possible consequences of each, and then select the solution that is best for public health. Here we present an overview on the existing and deeming regulatory decisions for electronic cigarettes. We challenge them, based on the mounting scientific evidence with the ultimate goal of proposing appropriate recommendations while minimizing potential unintended consequences of ill-informed regulation. PMID:24587890

  12. Electronic Cigarette and Traditional Cigarette Use among Middle and High School Students in Florida, 2011-2014.

    PubMed

    Porter, Lauren; Duke, Jennifer; Hennon, Meredith; Dekevich, David; Crankshaw, Erik; Homsi, Ghada; Farrelly, Matthew

    2015-01-01

    Recent youth trends in the prevalence of e-cigarette and traditional cigarette use in Florida were examined in a cross-sectional, representative state sample from 2011 to 2014. Traditional cigarette use among youth declined during the study period. Experimentation with and past 30-day use of e-cigarettes among Florida youth tripled over 4 years. Past 30-day e-cigarette use exceeded traditional cigarette use in 2014; 10.8% of high school and 4.0% of middle school students reported recent e-cigarette use, compared with 8.7% of high school and 2.9% of middle school students for traditional cigarettes (P<0.001). By 2014, 20.5% of high school and 8.5% of middle school students reported ever use of e-cigarettes. Among ever e-cigarette users in 2014, 30.3% of high school and 42.2% of middle school students had never smoked traditional cigarettes. Given the concern that significant rates of e-cigarette use by U.S. adolescents may have a negative effect on public health, further review of e-cigarette advertising, marketing, sales, and use among U.S. youth is warranted.

  13. FDA to Weigh Dangers of Exploding E-Cigarettes

    MedlinePlus

    ... FDA had identified 66 instances of e-cigarette explosions in 2015 and early 2016. The batteries overheated, ... that e-cigarettes pose no more fire or explosion risk than other devices that rely on lithium- ...

  14. Just 1 Cigarette a Day Can Be Deadly

    MedlinePlus

    ... news/fullstory_162365.html Just 1 Cigarette a Day Can Be Deadly: Study Light smokers still faced ... HealthDay News) -- Think smoking just one cigarette a day is harmless? Think again, a new study says. ...

  15. Most Americans Favor Larger Health Warnings on Cigarette Packs

    MedlinePlus

    ... html Most Americans Favor Larger Health Warnings on Cigarette Packs Even many smokers think these warnings should ... 31, 2017 FRIDAY, March 31, 2017 (HealthDay News) -- Cigarette packs carry health warnings, but many Americans think ...

  16. Lung injury after cigarette smoking is particle-related

    EPA Science Inventory

    That specific component responsible and the mechanistic pathway for increased human morbidity and mortality after cigarette smoking have yet to be delineated. We propose that 1) injury and disease following cigarette smoking are associated with exposure and retention of particles...

  17. More Americans Questioning Safety of E-Cigarettes

    MedlinePlus

    ... cigarettes, new research finds. Public perception about these battery-operated devices is changing, even though studies investigating ... in April to examine the dangers of exploding batteries in e-cigarettes. The agency identified 66 instances ...

  18. Protein phosphatase Mg2+/Mn2+ dependent 1F promotes smoking-induced breast cancer by inactivating phosphorylated-p53-induced signals

    PubMed Central

    Tu, Shih-Hsin; Lin, Yin-Ching; Huang, Chi-Cheng; Yang, Po-Sheng; Chang, Hui-Wen; Chang, Chien-Hsi; Wu, Chih-Hsiung; Chen, Li-Ching; Ho, Yuan-Soon

    2016-01-01

    We previously demonstrated that the activation of α9-nicotinic acetylcholine receptor (α9-nAchR) signaling by smoking promotes breast cancer formation. To investigate the downstream signaling molecules involved in α9-nAChR-induced breast tumorigenesis, we used real-time polymerase chain reactions and Western blotting to assess expression of protein phosphatase Mg2+/Mn2+ dependent 1F (PPM1F), a Ser/Thr protein phosphatase, in human breast cancer samples (n=167). Additionally, stable PPM1F-knockdown and -overexpressing cell lines were established to evaluate the function of PPM1F. The phosphatase activity of PPM1F in nicotine-treated cells was assessed through Western blotting, confocal microscopy, and fluorescence resonance energy transfer. Higher levels of PPM1F were detected in the breast cancer tissues of heavy smokers (n=7, 12.8-fold) greater than of non-smokers (n= 28, 6.3-fold) (**p=0.01). In vitro, nicotine induced PPM1F expression, whereas α9-nAChR knockdown reduced the protein expression of PPM1F. A series of biochemical experiments using nicotine-treated cells suggested that the dephosphorylation of p53 (Ser-20) and BAX (Ser-184) by PPM1F is a critical posttranslational modification, as observed in breast cancer patients who were heavy smokers. These observations indicate that PPM1F may be a mediator downstream of α9-nAChR that activates smoking-induced carcinogenic signals. Thus, PPM1F expression could be used for prognostic diagnosis or inhibited for cancer prevention and therapy. PMID:27769050

  19. Association between Peer Cigarette Smoking and Electronic Cigarette Smoking among Adolescent Nonsmokers: A National Representative Survey

    PubMed Central

    Hwang, Jun Hyun; Park, Soon-Woo

    2016-01-01

    We assessed the association between electronic cigarette (e-cigarette) use and peer cigarette smoking, a major risk factor for the initiation of cigarette smoking in adolescents. Data from the 2013 Korea Youth Risk Behavior Web-based Survey of 65,753 nonsmokers aged 13–18 years were analyzed using multiple logistic regression. A total of 3.8% of the Korean adolescents were ‘ever e-cigarette’ users and 1.2% were current users. Adjusted odds ratios (ORs) for current and ever e-cigarette use compared to those whose closest friends were non-smokers ranged from 2.05 (95% confidence interval [CI], 1.82–2.30) to 5.50 (95% CI, 4.77–6.34), and from 2.23 (95% CI, 1.77–2.81) to 7.82 (95% CI, 5.97–10.25) for those who had ‘some’ close friends to ‘most/all’ friends who smoked, respectively. The slopes of the adjusted ORs for e-cigarette use in ‘never smokers’ were more than twice as steep as those in ‘former smokers’, showing a significant interaction effect between the proportion of smoking closest friends and cigarette smoking status (never or former smokers) (p<0.001 for interaction). Peer cigarette smoking had a significant association with e-cigarette use in adolescent nonsmokers, and this association was greater on never smokers than former smokers. PMID:27695093

  20. Cigarette advertising to counter New Year's resolutions.

    PubMed

    Basil, M D; Basil, D Z; Schooler, C

    2000-01-01

    One process through which tobacco advertising may work is by reducing rates of quitting. Theories of addiction support the notion that relapse can be prompted by environmental cues. Further, because withdrawal symptoms occur over a predictable time frame, and because the most popular time to quit smoking is the beginning of the year, as a New Year's resolution, tobacco companies can make use of advertising to remind quitters of their need to smoke. Study 1 examined advertising in 10 popular magazines. It found a higher number of ads in January and February than the rest of the year after 1984. Study 2 examined cigarette advertising on the back cover of 10 other popular magazines. This study also found a higher rate of cigarette advertisements in January and February than for the rest of the year. The results suggest that cigarette marketers may be attempting to preempt quitting by cuing smoking behavior.

  1. Cigarette smoking and invasive cervical cancer

    SciTech Connect

    Brinton, L.A.; Schairer, C.; Haenszel, W.; Stolley, P.; Lehman, H.F.; Levine, R.; Savitz, D.A.

    1986-06-20

    A case-control study of 480 patients with invasive cervical cancer and 797 population controls, conducted in five geographic areas in the United States, included an evaluation of the relationship of several cigarette smoking variables to cervical cancer risk. Although smoking was correlated with both age at first intercourse and number of sexual partners, a significant smoking-related risk persisted for squamous cell carcinoma after adjustment for these factors (relative risk, 1.5). Twofold excess risks were seen for those smoking 40 or more cigarettes per day and those smoking for 40 or more years. Increased risks, however, were observed only among recent and continuous smokers. In contrast to squamous cell cancer, no relationship was observed between smoking and risk of adenocarcinoma or adenosquamous carcinoma. These results suggest a causal relationship between cigarette smoking and invasive squamous cell cervical cancer, perhaps through a late-stage or promotional event, although the mechanisms of action require further elucidation.

  2. Women, smoking, cigarette advertising and cancer.

    PubMed

    Ernster, V L

    1986-01-01

    Cigarette smoking is a major cause of cancer in women, accounting for about one-fourth of their estimated 219,000 cancer deaths per year. Cigarette smoking specifically increases a woman's risk of developing cancer of the lung, larynx, esophagus, oral cavity, pancreas, kidney, bladder, and possibly uterine cervix. During the past twenty years, concerted efforts have been made by the tobacco industry to increase sales to women. Strategies have included development of "feminine" brands such as Virginia Slims, slick media campaigns portraying smoking as elegant and glamorous, and sponsorship of fashion, women's sports events, and even medical programs. Reversal of these alarming trends requires that women as well as men recognize the role of cigarette smoking in cancer causation, and support programs which promote non-smoking as well as combat the influence of the tobacco industry on women's smoking behavior.

  3. Where Manitoba children obtain their cigarettes.

    PubMed Central

    Stanwick, R S; Fish, D G; Manfreda, J; Gelskey, D; Skuba, A

    1987-01-01

    People who start to smoke as children put themselves at greater risk of dying prematurely or being disabled by tobacco-induced disease. One solution is to restrict children's access to cigarettes, thereby reducing consumption of the product and, ultimately, damage to health. This study found that in 1985 the majority of Manitoba public school children 8 to 15 years of age who smoked "regularly" (defined as usually every day) obtained their cigarettes from stores. This source could be reduced, if not eliminated, were a federal regulation passed in 1908 enforced. Under Canada's Tobacco Restraint Act it is illegal for merchants to sell tobacco to anyone under the age of 16 years. By implementing this existing law, authorities would not only be keeping the profit from almost a million dollars in cigarette sales in Manitoba alone out of tobacco company coffers but also be having an impact on the leading cause of preventable premature death and disability in Canada. PMID:3621098

  4. Triple Quad-ICP-MS Measurement of Toxic Metals in Mainstream Cigarette Smoke from Spectrum Research Cigarettes.

    PubMed

    Pappas, R Steven; Gray, Naudia; Gonzalez-Jimenez, Nathalie; Fresquez, Mark; Watson, Clifford H

    2016-01-01

    We previously reported toxic metal concentrations in the mainstream smoke from 50 varieties of commercial cigarettes available in the USA using quadrupole inductively coupled plasma-mass spectrometry (ICP-MS). However, efforts to continue producing high quality data on select mainstream cigarette smoke constituents demand continued improvements in instrumentation and methodology and application of the methodology to cigarettes that differ in design or construction. Here we report a new application of 'triple quad'-ICP-MS instrumentation to analyze seven toxic metals in mainstream cigarette smoke from the Spectrum variable nicotine research cigarettes. The Spectrum cigarettes are available for research purposes in different configurations of low or conventional levels of nicotine, mentholated or nonmentholated, and tar delivery ranges described as 'low tar' or 'high tar'. Detailed characterizations of specific harmful or potentially harmful constituents delivered by these research cigarettes will help inform researchers using these cigarettes in exposure studies, cessation studies and studies related to nicotine addiction or compensation.

  5. Changes in Adolescent Cigarette-Brand Preference, 1989 to 1996

    ERIC Educational Resources Information Center

    Kaufman, Nancy J.; Castrucci, Brian C.; Mowery, Paul; Gerlach, Karen K.; Emont, Seth; Orleans, C. Tracy

    2004-01-01

    Objective: To understand changes in cigarette-brand choice by adolescents in the context of demographic differences and advertising. Methods: Data from 3 nationally representative cross-sectional surveys of adolescents were analyzed. Results: Marlboro, Camel, and Newport brand cigarettes accounted for over 80% of the cigarettes usually bought by…

  6. CDC Vital Signs: E-cigarette Ads and Youth

    MedlinePlus

    ... en Español [PDF - 2.7 MB] CDC Digital Press Kit Read the MMWR Science Clips E-cigarette Ads and ... 2.4 million middle and high school students were current (past 30-day) users of electronic cigarettes, or e-cigarettes, in 2014. Most e- ...

  7. Cigarette staining and cleaning of a maxillofacial silicone

    SciTech Connect

    Yu, R.; Koran, A.; Raptis, C.N.; Craig, R.G.

    1983-07-01

    In this study, a maxillofacial silicone elastomer was stained with cigarette smoke. The stain was then removed by solvent extraction using 1,1,1-trichloroethane. The cigarette smoke produced large color changes in the elastomer as measured from spectrophotometric reflectance curves. The solvent was totally effective in removing the cigarette stain without changing the color of the silicone base.

  8. 27 CFR 40.24 - Classification of cigarettes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cigarettes. 40.24 Section 40.24 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes § 40.24 Classification of cigarettes. For tax purposes,...

  9. 27 CFR 40.24 - Classification of cigarettes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cigarettes. 40.24 Section 40.24 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes § 40.24 Classification of cigarettes. For tax purposes,...

  10. 27 CFR 40.24 - Classification of cigarettes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... cigarettes. 40.24 Section 40.24 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes § 40.24 Classification of cigarettes. For tax purposes,...

  11. 16 CFR 1210.3 - Requirements for cigarette lighters.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Requirements for cigarette lighters. 1210.3... REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.3 Requirements for cigarette lighters. (a) A lighter subject to this part 1210 shall be resistant to successful operation by...

  12. Food and Drug Administration Evaluation and Cigarette Smoking Risk Perceptions

    ERIC Educational Resources Information Center

    Kaufman, Annette R.; Waters, Erika A.; Parascandola, Mark; Augustson, Erik M.; Bansal-Travers, Maansi; Hyland, Andrew; Cummings, K. Michael

    2011-01-01

    Objectives: To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…

  13. 21 CFR 1141.14 - Misbranding of cigarettes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Misbranding of cigarettes. 1141.14 Section 1141.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) TOBACCO PRODUCTS CIGARETTE PACKAGE AND ADVERTISING WARNINGS Cigarette Package and Advertising...

  14. 21 CFR 1141.14 - Misbranding of cigarettes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Misbranding of cigarettes. 1141.14 Section 1141.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) TOBACCO PRODUCTS CIGARETTE PACKAGE AND ADVERTISING WARNINGS Cigarette Package and Advertising...

  15. 27 CFR 41.74 - Notice for cigarettes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... product contained therein; and the classification for tax purposes, i.e., for small cigarettes either... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Notice for cigarettes. 41..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND...

  16. 27 CFR 40.215 - Notice for cigarettes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... product contained therein, and the classification for tax purposes, i.e., for small cigarettes, either... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Notice for cigarettes. 40..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND...

  17. 27 CFR 45.45 - Notice for cigarettes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... contained therein, and the classification for tax purposes, i.e., for small cigarettes, either “small” or... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Notice for cigarettes. 45..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO REMOVAL OF TOBACCO PRODUCTS AND CIGARETTE PAPERS AND...

  18. 27 CFR 40.24 - Classification of cigarettes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cigarettes. 40.24 Section 40.24 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTME