ingest cdrApp 2018-06-13T20:49:26.906Z 51cd2fe2-3fd7-401f-a923-a97bc3db68a2 modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T22:17:15.532Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2018-06-13T22:17:27.232Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2018-06-13T22:17:50.347Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T22:18:13.328Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-11T02:27:33.792Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-15T18:58:02.810Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-21T19:19:40.078Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-26T22:32:06.909Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-11T23:11:08.855Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-20T16:54:03.271Z Phillip Clapp Author Curriculum in Toxicology School of Medicine MODIFICATION OF RESPIRATORY SYSTEM INNATE DEFENSE MECHANISMS BY FLAVORING AGENTS IN ELECTRONIC CIGARETTES Electronic cigarettes (e-cigarettes) have emerged as a potentially safer alternative to traditional cigarettes. Because e-cigarettes deliver nicotine without burning tobacco, their use likely confers a lower overall health risk than inhaling combustible tobacco products. However, e-cigarette emissions contain solvents (propylene glycol and glycerol), flavorings, and other additives, which have not been evaluated for inhalation toxicities. The inhalation of flavoring agents, which are frequently aldehydes, poses a significant unknown in regards to the potential health risks of e-cigarette use as many of these chemicals are structurally similar to toxic aldehydes in cigarette smoke. Furthermore, aldehyde flavoring agents are often used at exceedingly high concentrations in e-cigarettes which may lead to high exposure doses. The work presented in this dissertation focuses on evaluating the effects of flavored e-cigarettes, particularly those containing ⍺,β-unsaturated cinnamaldehyde, on respiratory innate defense mechanisms and assessing whether and how these flavorings may alter susceptibility to respiratory infections. In Chapter 2, we report that cinnamon-flavored e-cigarette refill liquids and cinnamaldehyde modify human respiratory innate immune cell defense functions, including neutrophil and alveolar macrophage phagocytosis, neutrophil extracellular trap formation, and natural killer (NK) cell-mediated killing of leukemia cells. Based on these observations we established the cinnamaldehyde exposure concentrations that inhibit normal defense functions (IC50) and induce cytotoxicity (LC50). In Chapter 3, we report that cinnamon-flavored e-liquids, cinnamon e-cigarette aerosols, and cinnamaldehyde temporarily suppress motile cilia on human bronchial epithelial cells (hBE) and that this response is driven by transient inhibition of mitochondrial respiration and glycolysis. In Chapter 4, we report that cinnamaldehyde, guaiacol, and eugenol elicit a dose-dependent bimodal effect on Nrf2-pathway activation in bronchial epithelial cells (Beas-2B) and cinnamaldehyde exposure significantly depletes cellular glutathione (GSH) levels at low micromolar concentrations. Taken together, the work presented in this dissertation demonstrates that flavoring agents, in the context of e-cigarette use, are capable of dysregulating essential respiratory defense responses, which may increase susceptibility of respiratory infections and lung disease in e-cigarette users. It is our hope that the information provided here will be useful in the development of health-protective policies aimed at reducing or eliminating harmful and potentially harmful chemicals from e-cigarettes. Spring 2018 2018 Toxicology cinnamaldehyde, e-cigarette, electronic cigarette, e-liquid, respiratory innate immunity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Toxicology Ilona Jaspers Thesis advisor Bernard Weissman Thesis advisor William Bennett Thesis advisor Beverly Koller Thesis advisor Mehdi Hazari Thesis advisor Terry Noah Thesis advisor text Phillip Clapp Author Curriculum in Toxicology School of Medicine MODIFICATION OF RESPIRATORY SYSTEM INNATE DEFENSE MECHANISMS BY FLAVORING AGENTS IN ELECTRONIC CIGARETTES Electronic cigarettes (e-cigarettes) have emerged as a potentially safer alternative to traditional cigarettes. Because e-cigarettes deliver nicotine without burning tobacco, their use likely confers a lower overall health risk than inhaling combustible tobacco products. However, e-cigarette emissions contain solvents (propylene glycol and glycerol), flavorings, and other additives, which have not been evaluated for inhalation toxicities. The inhalation of flavoring agents, which are frequently aldehydes, poses a significant unknown in regards to the potential health risks of e-cigarette use as many of these chemicals are structurally similar to toxic aldehydes in cigarette smoke. Furthermore, aldehyde flavoring agents are often used at exceedingly high concentrations in e-cigarettes which may lead to high exposure doses. The work presented in this dissertation focuses on evaluating the effects of flavored e-cigarettes, particularly those containing ⍺,β-unsaturated cinnamaldehyde, on respiratory innate defense mechanisms and assessing whether and how these flavorings may alter susceptibility to respiratory infections. In Chapter 2, we report that cinnamon-flavored e-cigarette refill liquids and cinnamaldehyde modify human respiratory innate immune cell defense functions, including neutrophil and alveolar macrophage phagocytosis, neutrophil extracellular trap formation, and natural killer (NK) cell-mediated killing of leukemia cells. Based on these observations we established the cinnamaldehyde exposure concentrations that inhibit normal defense functions (IC50) and induce cytotoxicity (LC50). In Chapter 3, we report that cinnamon-flavored e-liquids, cinnamon e-cigarette aerosols, and cinnamaldehyde temporarily suppress motile cilia on human bronchial epithelial cells (hBE) and that this response is driven by transient inhibition of mitochondrial respiration and glycolysis. In Chapter 4, we report that cinnamaldehyde, guaiacol, and eugenol elicit a dose-dependent bimodal effect on Nrf2-pathway activation in bronchial epithelial cells (Beas-2B) and cinnamaldehyde exposure significantly depletes cellular glutathione (GSH) levels at low micromolar concentrations. Taken together, the work presented in this dissertation demonstrates that flavoring agents, in the context of e-cigarette use, are capable of dysregulating essential respiratory defense responses, which may increase susceptibility of respiratory infections and lung disease in e-cigarette users. It is our hope that the information provided here will be useful in the development of health-protective policies aimed at reducing or eliminating harmful and potentially harmful chemicals from e-cigarettes. Spring 2018 2018 Toxicology cinnamaldehyde, e-cigarette, electronic cigarette, e-liquid, respiratory innate immunity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Toxicology Ilona Jaspers Thesis advisor Bernard Weissman Thesis advisor William Bennett Thesis advisor Beverly Koller Thesis advisor Mehdi Hazari Thesis advisor Terry Noah Thesis advisor text Phillip Clapp Author Curriculum in Toxicology School of Medicine MODIFICATION OF RESPIRATORY SYSTEM INNATE DEFENSE MECHANISMS BY FLAVORING AGENTS IN ELECTRONIC CIGARETTES Electronic cigarettes (e-cigarettes) have emerged as a potentially safer alternative to traditional cigarettes. Because e-cigarettes deliver nicotine without burning tobacco, their use likely confers a lower overall health risk than inhaling combustible tobacco products. However, e-cigarette emissions contain solvents (propylene glycol and glycerol), flavorings, and other additives, which have not been evaluated for inhalation toxicities. The inhalation of flavoring agents, which are frequently aldehydes, poses a significant unknown in regards to the potential health risks of e-cigarette use as many of these chemicals are structurally similar to toxic aldehydes in cigarette smoke. Furthermore, aldehyde flavoring agents are often used at exceedingly high concentrations in e-cigarettes which may lead to high exposure doses. The work presented in this dissertation focuses on evaluating the effects of flavored e-cigarettes, particularly those containing ⍺,β-unsaturated cinnamaldehyde, on respiratory innate defense mechanisms and assessing whether and how these flavorings may alter susceptibility to respiratory infections. In Chapter 2, we report that cinnamon-flavored e-cigarette refill liquids and cinnamaldehyde modify human respiratory innate immune cell defense functions, including neutrophil and alveolar macrophage phagocytosis, neutrophil extracellular trap formation, and natural killer (NK) cell-mediated killing of leukemia cells. Based on these observations we established the cinnamaldehyde exposure concentrations that inhibit normal defense functions (IC50) and induce cytotoxicity (LC50). In Chapter 3, we report that cinnamon-flavored e-liquids, cinnamon e-cigarette aerosols, and cinnamaldehyde temporarily suppress motile cilia on human bronchial epithelial cells (hBE) and that this response is driven by transient inhibition of mitochondrial respiration and glycolysis. In Chapter 4, we report that cinnamaldehyde, guaiacol, and eugenol elicit a dose-dependent bimodal effect on Nrf2-pathway activation in bronchial epithelial cells (Beas-2B) and cinnamaldehyde exposure significantly depletes cellular glutathione (GSH) levels at low micromolar concentrations. Taken together, the work presented in this dissertation demonstrates that flavoring agents, in the context of e-cigarette use, are capable of dysregulating essential respiratory defense responses, which may increase susceptibility of respiratory infections and lung disease in e-cigarette users. It is our hope that the information provided here will be useful in the development of health-protective policies aimed at reducing or eliminating harmful and potentially harmful chemicals from e-cigarettes. Spring 2018 2018 Toxicology cinnamaldehyde, e-cigarette, electronic cigarette, e-liquid, respiratory innate immunity eng Doctor of Philosophy Dissertation Toxicology Ilona Jaspers Thesis advisor Bernard Weissman Thesis advisor William Bennett Thesis advisor Beverly H. Koller Thesis advisor Mehdi Hazari Thesis advisor Terry Noah Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Phillip Clapp Author Curriculum in Toxicology School of Medicine MODIFICATION OF RESPIRATORY SYSTEM INNATE DEFENSE MECHANISMS BY FLAVORING AGENTS IN ELECTRONIC CIGARETTES Electronic cigarettes (e-cigarettes) have emerged as a potentially safer alternative to traditional cigarettes. Because e-cigarettes deliver nicotine without burning tobacco, their use likely confers a lower overall health risk than inhaling combustible tobacco products. However, e-cigarette emissions contain solvents (propylene glycol and glycerol), flavorings, and other additives, which have not been evaluated for inhalation toxicities. The inhalation of flavoring agents, which are frequently aldehydes, poses a significant unknown in regards to the potential health risks of e-cigarette use as many of these chemicals are structurally similar to toxic aldehydes in cigarette smoke. Furthermore, aldehyde flavoring agents are often used at exceedingly high concentrations in e-cigarettes which may lead to high exposure doses. The work presented in this dissertation focuses on evaluating the effects of flavored e-cigarettes, particularly those containing ⍺,β-unsaturated cinnamaldehyde, on respiratory innate defense mechanisms and assessing whether and how these flavorings may alter susceptibility to respiratory infections. In Chapter 2, we report that cinnamon-flavored e-cigarette refill liquids and cinnamaldehyde modify human respiratory innate immune cell defense functions, including neutrophil and alveolar macrophage phagocytosis, neutrophil extracellular trap formation, and natural killer (NK) cell-mediated killing of leukemia cells. Based on these observations we established the cinnamaldehyde exposure concentrations that inhibit normal defense functions (IC50) and induce cytotoxicity (LC50). In Chapter 3, we report that cinnamon-flavored e-liquids, cinnamon e-cigarette aerosols, and cinnamaldehyde temporarily suppress motile cilia on human bronchial epithelial cells (hBE) and that this response is driven by transient inhibition of mitochondrial respiration and glycolysis. In Chapter 4, we report that cinnamaldehyde, guaiacol, and eugenol elicit a dose-dependent bimodal effect on Nrf2-pathway activation in bronchial epithelial cells (Beas-2B) and cinnamaldehyde exposure significantly depletes cellular glutathione (GSH) levels at low micromolar concentrations. Taken together, the work presented in this dissertation demonstrates that flavoring agents, in the context of e-cigarette use, are capable of dysregulating essential respiratory defense responses, which may increase susceptibility of respiratory infections and lung disease in e-cigarette users. It is our hope that the information provided here will be useful in the development of health-protective policies aimed at reducing or eliminating harmful and potentially harmful chemicals from e-cigarettes. Spring 2018 2018 Toxicology cinnamaldehyde, e-cigarette, electronic cigarette, e-liquid, respiratory innate immunity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Toxicology Ilona Jaspers Thesis advisor Bernard Weissman Thesis advisor William Bennett Thesis advisor Beverly Koller Thesis advisor Mehdi Hazari Thesis advisor Terry Noah Thesis advisor text Phillip Clapp Creator Curriculum in Toxicology School of Medicine MODIFICATION OF RESPIRATORY SYSTEM INNATE DEFENSE MECHANISMS BY FLAVORING AGENTS IN ELECTRONIC CIGARETTES Electronic cigarettes (e-cigarettes) have emerged as a potentially safer alternative to traditional cigarettes. Because e-cigarettes deliver nicotine without burning tobacco, their use likely confers a lower overall health risk than inhaling combustible tobacco products. However, e-cigarette emissions contain solvents (propylene glycol and glycerol), flavorings, and other additives, which have not been evaluated for inhalation toxicities. The inhalation of flavoring agents, which are frequently aldehydes, poses a significant unknown in regards to the potential health risks of e-cigarette use as many of these chemicals are structurally similar to toxic aldehydes in cigarette smoke. Furthermore, aldehyde flavoring agents are often used at exceedingly high concentrations in e-cigarettes which may lead to high exposure doses. The work presented in this dissertation focuses on evaluating the effects of flavored e-cigarettes, particularly those containing ⍺,β-unsaturated cinnamaldehyde, on respiratory innate defense mechanisms and assessing whether and how these flavorings may alter susceptibility to respiratory infections. In Chapter 2, we report that cinnamon-flavored e-cigarette refill liquids and cinnamaldehyde modify human respiratory innate immune cell defense functions, including neutrophil and alveolar macrophage phagocytosis, neutrophil extracellular trap formation, and natural killer (NK) cell-mediated killing of leukemia cells. Based on these observations we established the cinnamaldehyde exposure concentrations that inhibit normal defense functions (IC50) and induce cytotoxicity (LC50). In Chapter 3, we report that cinnamon-flavored e-liquids, cinnamon e-cigarette aerosols, and cinnamaldehyde temporarily suppress motile cilia on human bronchial epithelial cells (hBE) and that this response is driven by transient inhibition of mitochondrial respiration and glycolysis. In Chapter 4, we report that cinnamaldehyde, guaiacol, and eugenol elicit a dose-dependent bimodal effect on Nrf2-pathway activation in bronchial epithelial cells (Beas-2B) and cinnamaldehyde exposure significantly depletes cellular glutathione (GSH) levels at low micromolar concentrations. Taken together, the work presented in this dissertation demonstrates that flavoring agents, in the context of e-cigarette use, are capable of dysregulating essential respiratory defense responses, which may increase susceptibility of respiratory infections and lung disease in e-cigarette users. It is our hope that the information provided here will be useful in the development of health-protective policies aimed at reducing or eliminating harmful and potentially harmful chemicals from e-cigarettes. Toxicology cinnamaldehyde; e-cigarette; electronic cigarette; e-liquid; respiratory innate immunity eng Doctor of Philosophy Dissertation Toxicology Ilona Jaspers Thesis advisor Bernard Weissman Thesis advisor William Bennett Thesis advisor Beverly H. Koller Thesis advisor Mehdi Hazari Thesis advisor Terry Noah Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution 2018 2018-05 Phillip Clapp Author Curriculum in Toxicology School of Medicine MODIFICATION OF RESPIRATORY SYSTEM INNATE DEFENSE MECHANISMS BY FLAVORING AGENTS IN ELECTRONIC CIGARETTES Electronic cigarettes (e-cigarettes) have emerged as a potentially safer alternative to traditional cigarettes. Because e-cigarettes deliver nicotine without burning tobacco, their use likely confers a lower overall health risk than inhaling combustible tobacco products. However, e-cigarette emissions contain solvents (propylene glycol and glycerol), flavorings, and other additives, which have not been evaluated for inhalation toxicities. The inhalation of flavoring agents, which are frequently aldehydes, poses a significant unknown in regards to the potential health risks of e-cigarette use as many of these chemicals are structurally similar to toxic aldehydes in cigarette smoke. Furthermore, aldehyde flavoring agents are often used at exceedingly high concentrations in e-cigarettes which may lead to high exposure doses. The work presented in this dissertation focuses on evaluating the effects of flavored e-cigarettes, particularly those containing ⍺,β-unsaturated cinnamaldehyde, on respiratory innate defense mechanisms and assessing whether and how these flavorings may alter susceptibility to respiratory infections. In Chapter 2, we report that cinnamon-flavored e-cigarette refill liquids and cinnamaldehyde modify human respiratory innate immune cell defense functions, including neutrophil and alveolar macrophage phagocytosis, neutrophil extracellular trap formation, and natural killer (NK) cell-mediated killing of leukemia cells. Based on these observations we established the cinnamaldehyde exposure concentrations that inhibit normal defense functions (IC50) and induce cytotoxicity (LC50). In Chapter 3, we report that cinnamon-flavored e-liquids, cinnamon e-cigarette aerosols, and cinnamaldehyde temporarily suppress motile cilia on human bronchial epithelial cells (hBE) and that this response is driven by transient inhibition of mitochondrial respiration and glycolysis. In Chapter 4, we report that cinnamaldehyde, guaiacol, and eugenol elicit a dose-dependent bimodal effect on Nrf2-pathway activation in bronchial epithelial cells (Beas-2B) and cinnamaldehyde exposure significantly depletes cellular glutathione (GSH) levels at low micromolar concentrations. Taken together, the work presented in this dissertation demonstrates that flavoring agents, in the context of e-cigarette use, are capable of dysregulating essential respiratory defense responses, which may increase susceptibility of respiratory infections and lung disease in e-cigarette users. It is our hope that the information provided here will be useful in the development of health-protective policies aimed at reducing or eliminating harmful and potentially harmful chemicals from e-cigarettes. Spring 2018 2018 Toxicology cinnamaldehyde, e-cigarette, electronic cigarette, e-liquid, respiratory innate immunity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Toxicology Ilona Jaspers Thesis advisor Bernard Weissman Thesis advisor William Bennett Thesis advisor Beverly H. Koller Thesis advisor Mehdi Hazari Thesis advisor Terry Noah Thesis advisor text Phillip Clapp Creator Curriculum in Toxicology School of Medicine Electronic cigarettes (e-cigarettes) have emerged as a potentially safer alternative to traditional cigarettes. Because e-cigarettes deliver nicotine without burning tobacco, their use likely confers a lower overall health risk than inhaling combustible tobacco products. However, e-cigarette emissions contain solvents (propylene glycol and glycerol), flavorings, and other additives, which have not been evaluated for inhalation toxicities. The inhalation of flavoring agents, which are frequently aldehydes, poses a significant unknown in regards to the potential health risks of e-cigarette use as many of these chemicals are structurally similar to toxic aldehydes in cigarette smoke. Furthermore, aldehyde flavoring agents are often used at exceedingly high concentrations in e-cigarettes which may lead to high exposure doses. The work presented in this dissertation focuses on evaluating the effects of flavored e-cigarettes, particularly those containing ⍺,β-unsaturated cinnamaldehyde, on respiratory innate defense mechanisms and assessing whether and how these flavorings may alter susceptibility to respiratory infections. In Chapter 2, we report that cinnamon-flavored e-cigarette refill liquids and cinnamaldehyde modify human respiratory innate immune cell defense functions, including neutrophil and alveolar macrophage phagocytosis, neutrophil extracellular trap formation, and natural killer (NK) cell-mediated killing of leukemia cells. Based on these observations we established the cinnamaldehyde exposure concentrations that inhibit normal defense functions (IC50) and induce cytotoxicity (LC50). In Chapter 3, we report that cinnamon-flavored e-liquids, cinnamon e-cigarette aerosols, and cinnamaldehyde temporarily suppress motile cilia on human bronchial epithelial cells (hBE) and that this response is driven by transient inhibition of mitochondrial respiration and glycolysis. In Chapter 4, we report that cinnamaldehyde, guaiacol, and eugenol elicit a dose-dependent bimodal effect on Nrf2-pathway activation in bronchial epithelial cells (Beas-2B) and cinnamaldehyde exposure significantly depletes cellular glutathione (GSH) levels at low micromolar concentrations. Taken together, the work presented in this dissertation demonstrates that flavoring agents, in the context of e-cigarette use, are capable of dysregulating essential respiratory defense responses, which may increase susceptibility of respiratory infections and lung disease in e-cigarette users. It is our hope that the information provided here will be useful in the development of health-protective policies aimed at reducing or eliminating harmful and potentially harmful chemicals from e-cigarettes. 2018-05 2018 Toxicology cinnamaldehyde; e-cigarette; electronic cigarette; e-liquid; respiratory innate immunity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Ilona Jaspers Thesis advisor Bernard Weissman Thesis advisor William Bennett Thesis advisor Beverly H. Koller Thesis advisor Mehdi Hazari Thesis advisor Terry Noah Thesis advisor text Clapp_unc_0153D_17801.pdf uuid:8f42f3cc-1818-4cdb-b1e3-476f9ca845ac 2020-06-13T00:00:00 2018-04-13T18:33:10Z proquest application/pdf 32338158