Alveolar macrophages form the first line of defense against inhaled droplets containing Mycobacte... more Alveolar macrophages form the first line of defense against inhaled droplets containing Mycobacterium tuberculosis by controlling mycobacterial growth and regulating T cell responses. CD4+ and gamma delta T cells, two major T cell subsets activated by M. tuberculosis, require accessory cells for activation. However, the ability of alveolar macrophages to function as accessory cells for T cell activation remains controversial. We sought to determine the ability of alveolar macrophages to serve as accessory cells for resting (HLA-DR-, IL-2R-) and activated (HLA-DR+, IL-2R+) gamma delta T cells in response to M. tuberculosis and its Ag, and to compare accessory cell function for gamma delta T cells of alveolar macrophages and blood monocytes obtained from the same donor. Alveolar macrophages were found to serve as accessory cells for both resting and activated gamma delta T cells in response to M. tuberculosis Ag. At high alveolar macrophage to T cell ratios (> 3:1), however, expans...
Nicotine is one of the major components of electronic cigarette (e-cigarette) emissions. Nicotyri... more Nicotine is one of the major components of electronic cigarette (e-cigarette) emissions. Nicotyrine is a product of nicotine dehydrogenation in e-vapor and is a known inhibitor of human cytochrome P450 enzyme, which mediates nicotine metabolism. However, the emission of nicotine and especially nicotyrine from e-cigarettes has not been studied under real-world vaping patterns. This study examined the impact of e-liquid composition, e-cigarette device power output, and vaping topography on nicotine and nicotyrine concentrations under real-world vaping patterns. The amount of nicotine emitted from e-cigarettes vaped at high e-liquid nicotine levels, high device power, and large puff volumes ranged from 0.365 μg/puff to 236 μg/puff and was comparable to the amount of nicotine emitted from regular cigarettes. E-cigarette coil temperatures (200-300 °C) favored the formation of nicotyrine: E-cigarette vaping generated 2- to 63-fold more nicotyrine per unit nicotine emission than convention...
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 1996
The aim of the study was to describe the epidemiology of AIDS dementia complex (ADC) in Europe an... more The aim of the study was to describe the epidemiology of AIDS dementia complex (ADC) in Europe and to assess the possible role of zidovudine therapy in preventing or delaying its occurrence. We used an inception cohort, with data collected retrospectively from patients' clinical records from 52 clinical centers in 17 countries across Europe. The subjects were 6,548 adult people with AIDS consecutively diagnosed from 1979 to 1989. The main outcome measures were codiagnosis of ADC at the time of AIDS diagnosis and ADC-free time after AIDS diagnosis. ADC was reported in 295 patients (4.5%) at the time of AIDS diagnosis and during follow-up in a further 402 of the 5,160 patients (7.8%) who were diagnosed with AIDS based on diseases other than ADC. Whether at the time of AIDS diagnosis or later, the occurrence of ADC was significantly associated with age, transmission category, and CD4+ cell counts. The risk was greater in older patients (14 and 19% greater, at AIDS diagnosis and after, respectively, for a 5-year difference in age), in i.v. drug users than in homosexual and bisexual men (89 and 60% greater, at AIDS diagnosis and after, respectively), and for people with lower CD4+ cell counts (14 and 30% greater for a reduction of 1 on the natural log scale). Risk was almost double for women than for men. A significant reduction, of approximately 40%, was found in the risk of developing ADC after AIDS diagnosis for patients receiving zidovudine therapy, but this effect was present only during the first 18 months of treatment, irrespective of whether treatment began before or after AIDS diagnosis. In conclusion, an increase in the risk of developing ADC either at the time of AIDS diagnosis or thereafter is associated with increasing age, i.v. drug use, and decreased CD4+ cell count. Women tend to have a higher risk of ADC at the time of AIDS diagnosis. Zidovudine therapy appears to have a definite, but time-limited, effect of protecting patients against ADC development after AIDS diagnosis.
International Journal of Environmental Research and Public Health, 2019
Tuberculosis (TB) and air pollution both contribute significantly to the global burden of disease... more Tuberculosis (TB) and air pollution both contribute significantly to the global burden of disease. Epidemiological studies show that exposure to household and urban air pollution increase the risk of new infections with Mycobacterium tuberculosis (M.tb) and the development of TB in persons infected with M.tb and alter treatment outcomes. There is increasing evidence that particulate matter (PM) exposure weakens protective antimycobacterial host immunity. Mechanisms by which exposure to urban PM may adversely affect M.tb-specific human T cell functions have not been studied. We, therefore, explored the effects of urban air pollution PM2.5 (aerodynamic diameters ≤2.5µm) on M.tb-specific T cell functions in human peripheral blood mononuclear cells (PBMC). PM2.5 exposure decreased the capacity of PBMC to control the growth of M.tb and the M.tb-induced expression of CD69, an early surface activation marker expressed on CD3+ T cells. PM2.5 exposure also decreased the production of IFN-γ i...
To assess biological risks of nanoparticle (NP) exposures, we examined the effects of silver (Ag)... more To assess biological risks of nanoparticle (NP) exposures, we examined the effects of silver (Ag) core Ag20-citrate (Ag20) and carbon black (CB) on human host innate immune responses to M.tb , a respiratory pathogen that causes tuberculosis. Human peripheral blood monocyte-derived macrophages (MDMs) were exposed to 1, 10, 25 and 50 μg/mL of Ag20 and CB for 4 and 24 h. At 4 h no significant cytotoxicity was observed with neither of the NPs at none of the concentrations examined relative to unexposed MDMs. At 24 h, viability of the MDMs was reduced by 60–70% and 20% following Ag20 and CB exposure, respectively, at doses ≥25 μg/mL. M.tb -induced host immune responses are mediated by the activation of TLR signalling pathways that culminate in NF-κB activation. Effects of Ag20 and CB (10μg/mL for 4 h, a nontoxic dose) on TLR signalling in M.tb -infected and uninfected MDMs were compared using a human TLR signaling pathway-specific profiler array. Ag20 exposure suppressed the M.tb -induce...
Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M... more Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M.tb infection and Tuberculosis (TB) development. Recently, we demonstrated that diesel exhaust particles and urban air pollution particulate matter (PM) impair human peripheral blood mononuclear cell (PBMC) and respiratory epithelial cell (A549) innate immune responses to M.tb via downregulation of TLR-dependent cytokines (IFN-γ, IL-1β IL-6, TNF-α), and antimicrobial peptides, respectively. Here we examined effects of real-world-derived air pollution PM from Iztapalapa, a municipality with high prevalence of air pollution and TB in Mexico City on innate and adaptive human immune responses to M.tb . Cytotoxic and inflammatory PBMC responses were examined upon exposure to PM2.5 (<2.5μm diameter) and PM10 (<10μm) from rainy, cold-dry and warm-dry weather seasons. PBMC from IGRA+ (immunodiagnostic evidence of M.tb exposure) and IGRA- donors were exposed for 20 hours to PM at 0.1, 1 and...
Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M... more Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M.tb infection and Tuberculosis (TB) development. Recently, we demonstrated that diesel exhaust particles and urban air pollution particulate matter (PM) impair human peripheral blood mononuclear cell (PBMC) and respiratory epithelial cell (A549) innate immune responses to M.tb via downregulation of TLR-dependent cytokines (IFN-γ, IL-1β IL-6, TNF-α), and antimicrobial peptides, respectively. Here we examined effects of real-world-derived air pollution PM from Iztapalapa, a municipality with high prevalence of air pollution and TB in Mexico City on innate and adaptive human immune responses to M.tb . Cytotoxic and inflammatory PBMC responses were examined upon exposure to PM2.5 (<2.5μm diameter) and PM10 (<10μm) from rainy, cold-dry and warm-dry weather seasons. PBMC from IGRA+ (immunodiagnostic evidence of M.tb exposure) and IGRA- donors were exposed for 20 hours to PM at 0.1, 1 and...
In this paper, we assessed the association (relative risk, RR) between the exposure to PM10 and P... more In this paper, we assessed the association (relative risk, RR) between the exposure to PM10 and PM2.5 (as a continuous variable and as categories of low or high pollution exposure) on the incidence of pulmonary tuberculosis (PTB) in Mexicali, Baja California, Mexico. We used a weekly, lagged multiple Poisson regression model. We observed a 10-week delayed effect for PM10 and PM2.5 in all PTB cases and in male cases with PTB. An 11-week delayed effect occurred in the female PTB cases. For all the PTB cases, the RR rose by 2.4% (95% CI: 2.1, 2.6, p<0.10) for each 10 µg/m3 increase of PM10 in the continuous exposure and by 3.6% (CI: 3.3, 4.0, p<0.05) in the high pollution exposure category, and by 3.2% (CI: 2.9, 3.4, p<0.05) for each 10 µg/m3 increase of PM2.5 in the continuous exposure and by 3.9% (CI: 3.6, 4.3, p<0.05) in the high pollution exposure category. In men, the RR rose by 2.8% (CI: 2.5, 3.1, p<0.10) for each 10 µg/m3 increase of PM10 in the continuous exposur...
International Journal of Environmental Research and Public Health, 2020
Health impacts of electronic cigarette (e-cigarette) vaping are associated with the harmful chemi... more Health impacts of electronic cigarette (e-cigarette) vaping are associated with the harmful chemicals emitted from e-cigarettes such as carbonyls. However, the levels of various carbonyl compounds under real-world vaping conditions have been understudied. This study evaluated the levels of carbonyl compounds (e.g., formaldehyde, acetaldehyde, glyoxal, and diacetyl, etc.) under various device settings (i.e., power output), vaping topographies, and e-liquid compositions (i.e., base liquid, flavor types). The results showed that e-vapor carbonyl levels were the highest under higher power outputs. The propylene glycol (PG)-based e-liquids generated higher formaldehyde and acetaldehyde than vegetable glycerin (VG)-based e-liquids. In addition, fruit flavored e-liquids (i.e., strawberry and dragon fruit) generated higher formaldehyde emissions than mint/menthol and creamy/sweet flavored e-liquids. While single-top coils formed 3.5-fold more formaldehyde per puff than conventional cigarett...
The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorpora... more The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorporating them, may lead to increased health risks from occupational and public exposures. There is currently limited information about the putative toxicity of AgNWs upon inhalation, and incomplete understanding of the properties that control their bioreactivity. The lung lining fluid (LLF), which contains phospholipids and surfactant proteins, represents a first contact site with the respiratory system. In this work, the impact of Dipalmitoylphosphatidylcholine (DPPC), Curosurf® and murine LLF on the stability of AgNWs was examined. Both the phospholipid and protein components of the LLF modified the dissolution kinetics of AgNWs, due to the formation of a lipid corona or aggregation of the AgNWs. Moreover, the hydrophilic, but neither the hydrophobic surfactant proteins nor the phospholipids, induced agglomeration of the AgNWs. Finally, the generation of a secondary population of nano-silv...
Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various c... more Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various cell types.In vitrocell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systemsin vitro, to develop a mechanistic mathematical model that can support analysis and prediction ofin vivoeffects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized usingin vitromeasurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includesin vitrocellular dosim...
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, Jan 5, 2015
The alveolar respiratory unit constitutes one of the main targets of inhaled nanoparticles; the e... more The alveolar respiratory unit constitutes one of the main targets of inhaled nanoparticles; the effect of engineered nanomaterials (NMs) on human health is largely unknown. Surfactant protein D (SP-D) is synthesized by alveolar type II epithelial cells and released into respiratory secretions; its main function is in immune defence, notably against inhaled microbes. SP-D also plays an important role in modulating an appropriate inflammatory response in the lung, and reduced SP-D is associated with a number of inflammatory lung diseases. Adsorption of SP-D to inhaled NMs may facilitate their removal via macrophage phagocytosis. This study addresses the hypothesis that the chemistry, size and surface modification of engineered NMs will impact on their interaction with, and adsorption of, SP-D. To this purpose, we have examined the interactions between SP-D in human lung lavage and two NMs, carbon nanotubes and polystyrene nanoparticles, with different surface functionalization. We hav...
ABSTRACTA major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysreg... more ABSTRACTA major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysregulation, thought to be reflected in upregulated proinflammatory cytokines leading to the symptoms that are characteristic of this illness. Because the symptoms worsen with physical exertion or sleep loss, we hypothesized that we could use these stressors to magnify the underlying potential pathogenic abnormalities in the cytokine systems of people with CFS. We conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines. These data do not support an important role of immune dysregulation in the genesis of stress-induced wor...
RationaleAssociations between urban (outdoor) airborne particulate matter (PM) exposure and TB an... more RationaleAssociations between urban (outdoor) airborne particulate matter (PM) exposure and TB and potential biological mechanisms are poorly explored.ObjectivesTo examine whether in vivo exposure to urban outdoor PM in Mexico City and in vitro exposure to urban outdoor PM2.5 (< 2.5 µm median aerodynamic diameter) alters human host immune cell responses to Mycobacterium tuberculosis.MethodsCellular toxicity (flow cytometry, proliferation assay (MTS assay)), M. tuberculosis and PM2.5 phagocytosis (microscopy), cytokine-producing cells (Enzyme-linked immune absorbent spot (ELISPOT)), and signalling pathway markers (western blot) were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from healthy, non-smoking, residents of Mexico City (n=35; 13 female, 22 male). In vivo-acquired PM burden in alveolar macrophages (AM) was measured by digital image analysis.Measurements and main resultsIn vitro exposure of AM to PM2.5 did not affect M. tuberculosis ...
Alveolar macrophages form the first line of defense against inhaled droplets containing Mycobacte... more Alveolar macrophages form the first line of defense against inhaled droplets containing Mycobacterium tuberculosis by controlling mycobacterial growth and regulating T cell responses. CD4+ and gamma delta T cells, two major T cell subsets activated by M. tuberculosis, require accessory cells for activation. However, the ability of alveolar macrophages to function as accessory cells for T cell activation remains controversial. We sought to determine the ability of alveolar macrophages to serve as accessory cells for resting (HLA-DR-, IL-2R-) and activated (HLA-DR+, IL-2R+) gamma delta T cells in response to M. tuberculosis and its Ag, and to compare accessory cell function for gamma delta T cells of alveolar macrophages and blood monocytes obtained from the same donor. Alveolar macrophages were found to serve as accessory cells for both resting and activated gamma delta T cells in response to M. tuberculosis Ag. At high alveolar macrophage to T cell ratios (> 3:1), however, expans...
Nicotine is one of the major components of electronic cigarette (e-cigarette) emissions. Nicotyri... more Nicotine is one of the major components of electronic cigarette (e-cigarette) emissions. Nicotyrine is a product of nicotine dehydrogenation in e-vapor and is a known inhibitor of human cytochrome P450 enzyme, which mediates nicotine metabolism. However, the emission of nicotine and especially nicotyrine from e-cigarettes has not been studied under real-world vaping patterns. This study examined the impact of e-liquid composition, e-cigarette device power output, and vaping topography on nicotine and nicotyrine concentrations under real-world vaping patterns. The amount of nicotine emitted from e-cigarettes vaped at high e-liquid nicotine levels, high device power, and large puff volumes ranged from 0.365 μg/puff to 236 μg/puff and was comparable to the amount of nicotine emitted from regular cigarettes. E-cigarette coil temperatures (200-300 °C) favored the formation of nicotyrine: E-cigarette vaping generated 2- to 63-fold more nicotyrine per unit nicotine emission than convention...
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 1996
The aim of the study was to describe the epidemiology of AIDS dementia complex (ADC) in Europe an... more The aim of the study was to describe the epidemiology of AIDS dementia complex (ADC) in Europe and to assess the possible role of zidovudine therapy in preventing or delaying its occurrence. We used an inception cohort, with data collected retrospectively from patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; clinical records from 52 clinical centers in 17 countries across Europe. The subjects were 6,548 adult people with AIDS consecutively diagnosed from 1979 to 1989. The main outcome measures were codiagnosis of ADC at the time of AIDS diagnosis and ADC-free time after AIDS diagnosis. ADC was reported in 295 patients (4.5%) at the time of AIDS diagnosis and during follow-up in a further 402 of the 5,160 patients (7.8%) who were diagnosed with AIDS based on diseases other than ADC. Whether at the time of AIDS diagnosis or later, the occurrence of ADC was significantly associated with age, transmission category, and CD4+ cell counts. The risk was greater in older patients (14 and 19% greater, at AIDS diagnosis and after, respectively, for a 5-year difference in age), in i.v. drug users than in homosexual and bisexual men (89 and 60% greater, at AIDS diagnosis and after, respectively), and for people with lower CD4+ cell counts (14 and 30% greater for a reduction of 1 on the natural log scale). Risk was almost double for women than for men. A significant reduction, of approximately 40%, was found in the risk of developing ADC after AIDS diagnosis for patients receiving zidovudine therapy, but this effect was present only during the first 18 months of treatment, irrespective of whether treatment began before or after AIDS diagnosis. In conclusion, an increase in the risk of developing ADC either at the time of AIDS diagnosis or thereafter is associated with increasing age, i.v. drug use, and decreased CD4+ cell count. Women tend to have a higher risk of ADC at the time of AIDS diagnosis. Zidovudine therapy appears to have a definite, but time-limited, effect of protecting patients against ADC development after AIDS diagnosis.
International Journal of Environmental Research and Public Health, 2019
Tuberculosis (TB) and air pollution both contribute significantly to the global burden of disease... more Tuberculosis (TB) and air pollution both contribute significantly to the global burden of disease. Epidemiological studies show that exposure to household and urban air pollution increase the risk of new infections with Mycobacterium tuberculosis (M.tb) and the development of TB in persons infected with M.tb and alter treatment outcomes. There is increasing evidence that particulate matter (PM) exposure weakens protective antimycobacterial host immunity. Mechanisms by which exposure to urban PM may adversely affect M.tb-specific human T cell functions have not been studied. We, therefore, explored the effects of urban air pollution PM2.5 (aerodynamic diameters ≤2.5µm) on M.tb-specific T cell functions in human peripheral blood mononuclear cells (PBMC). PM2.5 exposure decreased the capacity of PBMC to control the growth of M.tb and the M.tb-induced expression of CD69, an early surface activation marker expressed on CD3+ T cells. PM2.5 exposure also decreased the production of IFN-γ i...
To assess biological risks of nanoparticle (NP) exposures, we examined the effects of silver (Ag)... more To assess biological risks of nanoparticle (NP) exposures, we examined the effects of silver (Ag) core Ag20-citrate (Ag20) and carbon black (CB) on human host innate immune responses to M.tb , a respiratory pathogen that causes tuberculosis. Human peripheral blood monocyte-derived macrophages (MDMs) were exposed to 1, 10, 25 and 50 μg/mL of Ag20 and CB for 4 and 24 h. At 4 h no significant cytotoxicity was observed with neither of the NPs at none of the concentrations examined relative to unexposed MDMs. At 24 h, viability of the MDMs was reduced by 60–70% and 20% following Ag20 and CB exposure, respectively, at doses ≥25 μg/mL. M.tb -induced host immune responses are mediated by the activation of TLR signalling pathways that culminate in NF-κB activation. Effects of Ag20 and CB (10μg/mL for 4 h, a nontoxic dose) on TLR signalling in M.tb -infected and uninfected MDMs were compared using a human TLR signaling pathway-specific profiler array. Ag20 exposure suppressed the M.tb -induce...
Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M... more Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M.tb infection and Tuberculosis (TB) development. Recently, we demonstrated that diesel exhaust particles and urban air pollution particulate matter (PM) impair human peripheral blood mononuclear cell (PBMC) and respiratory epithelial cell (A549) innate immune responses to M.tb via downregulation of TLR-dependent cytokines (IFN-γ, IL-1β IL-6, TNF-α), and antimicrobial peptides, respectively. Here we examined effects of real-world-derived air pollution PM from Iztapalapa, a municipality with high prevalence of air pollution and TB in Mexico City on innate and adaptive human immune responses to M.tb . Cytotoxic and inflammatory PBMC responses were examined upon exposure to PM2.5 (<2.5μm diameter) and PM10 (<10μm) from rainy, cold-dry and warm-dry weather seasons. PBMC from IGRA+ (immunodiagnostic evidence of M.tb exposure) and IGRA- donors were exposed for 20 hours to PM at 0.1, 1 and...
Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M... more Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M.tb infection and Tuberculosis (TB) development. Recently, we demonstrated that diesel exhaust particles and urban air pollution particulate matter (PM) impair human peripheral blood mononuclear cell (PBMC) and respiratory epithelial cell (A549) innate immune responses to M.tb via downregulation of TLR-dependent cytokines (IFN-γ, IL-1β IL-6, TNF-α), and antimicrobial peptides, respectively. Here we examined effects of real-world-derived air pollution PM from Iztapalapa, a municipality with high prevalence of air pollution and TB in Mexico City on innate and adaptive human immune responses to M.tb . Cytotoxic and inflammatory PBMC responses were examined upon exposure to PM2.5 (<2.5μm diameter) and PM10 (<10μm) from rainy, cold-dry and warm-dry weather seasons. PBMC from IGRA+ (immunodiagnostic evidence of M.tb exposure) and IGRA- donors were exposed for 20 hours to PM at 0.1, 1 and...
In this paper, we assessed the association (relative risk, RR) between the exposure to PM10 and P... more In this paper, we assessed the association (relative risk, RR) between the exposure to PM10 and PM2.5 (as a continuous variable and as categories of low or high pollution exposure) on the incidence of pulmonary tuberculosis (PTB) in Mexicali, Baja California, Mexico. We used a weekly, lagged multiple Poisson regression model. We observed a 10-week delayed effect for PM10 and PM2.5 in all PTB cases and in male cases with PTB. An 11-week delayed effect occurred in the female PTB cases. For all the PTB cases, the RR rose by 2.4% (95% CI: 2.1, 2.6, p<0.10) for each 10 µg/m3 increase of PM10 in the continuous exposure and by 3.6% (CI: 3.3, 4.0, p<0.05) in the high pollution exposure category, and by 3.2% (CI: 2.9, 3.4, p<0.05) for each 10 µg/m3 increase of PM2.5 in the continuous exposure and by 3.9% (CI: 3.6, 4.3, p<0.05) in the high pollution exposure category. In men, the RR rose by 2.8% (CI: 2.5, 3.1, p<0.10) for each 10 µg/m3 increase of PM10 in the continuous exposur...
International Journal of Environmental Research and Public Health, 2020
Health impacts of electronic cigarette (e-cigarette) vaping are associated with the harmful chemi... more Health impacts of electronic cigarette (e-cigarette) vaping are associated with the harmful chemicals emitted from e-cigarettes such as carbonyls. However, the levels of various carbonyl compounds under real-world vaping conditions have been understudied. This study evaluated the levels of carbonyl compounds (e.g., formaldehyde, acetaldehyde, glyoxal, and diacetyl, etc.) under various device settings (i.e., power output), vaping topographies, and e-liquid compositions (i.e., base liquid, flavor types). The results showed that e-vapor carbonyl levels were the highest under higher power outputs. The propylene glycol (PG)-based e-liquids generated higher formaldehyde and acetaldehyde than vegetable glycerin (VG)-based e-liquids. In addition, fruit flavored e-liquids (i.e., strawberry and dragon fruit) generated higher formaldehyde emissions than mint/menthol and creamy/sweet flavored e-liquids. While single-top coils formed 3.5-fold more formaldehyde per puff than conventional cigarett...
The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorpora... more The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorporating them, may lead to increased health risks from occupational and public exposures. There is currently limited information about the putative toxicity of AgNWs upon inhalation, and incomplete understanding of the properties that control their bioreactivity. The lung lining fluid (LLF), which contains phospholipids and surfactant proteins, represents a first contact site with the respiratory system. In this work, the impact of Dipalmitoylphosphatidylcholine (DPPC), Curosurf® and murine LLF on the stability of AgNWs was examined. Both the phospholipid and protein components of the LLF modified the dissolution kinetics of AgNWs, due to the formation of a lipid corona or aggregation of the AgNWs. Moreover, the hydrophilic, but neither the hydrophobic surfactant proteins nor the phospholipids, induced agglomeration of the AgNWs. Finally, the generation of a secondary population of nano-silv...
Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various c... more Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various cell types.In vitrocell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systemsin vitro, to develop a mechanistic mathematical model that can support analysis and prediction ofin vivoeffects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized usingin vitromeasurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includesin vitrocellular dosim...
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, Jan 5, 2015
The alveolar respiratory unit constitutes one of the main targets of inhaled nanoparticles; the e... more The alveolar respiratory unit constitutes one of the main targets of inhaled nanoparticles; the effect of engineered nanomaterials (NMs) on human health is largely unknown. Surfactant protein D (SP-D) is synthesized by alveolar type II epithelial cells and released into respiratory secretions; its main function is in immune defence, notably against inhaled microbes. SP-D also plays an important role in modulating an appropriate inflammatory response in the lung, and reduced SP-D is associated with a number of inflammatory lung diseases. Adsorption of SP-D to inhaled NMs may facilitate their removal via macrophage phagocytosis. This study addresses the hypothesis that the chemistry, size and surface modification of engineered NMs will impact on their interaction with, and adsorption of, SP-D. To this purpose, we have examined the interactions between SP-D in human lung lavage and two NMs, carbon nanotubes and polystyrene nanoparticles, with different surface functionalization. We hav...
ABSTRACTA major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysreg... more ABSTRACTA major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysregulation, thought to be reflected in upregulated proinflammatory cytokines leading to the symptoms that are characteristic of this illness. Because the symptoms worsen with physical exertion or sleep loss, we hypothesized that we could use these stressors to magnify the underlying potential pathogenic abnormalities in the cytokine systems of people with CFS. We conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines. These data do not support an important role of immune dysregulation in the genesis of stress-induced wor...
RationaleAssociations between urban (outdoor) airborne particulate matter (PM) exposure and TB an... more RationaleAssociations between urban (outdoor) airborne particulate matter (PM) exposure and TB and potential biological mechanisms are poorly explored.ObjectivesTo examine whether in vivo exposure to urban outdoor PM in Mexico City and in vitro exposure to urban outdoor PM2.5 (< 2.5 µm median aerodynamic diameter) alters human host immune cell responses to Mycobacterium tuberculosis.MethodsCellular toxicity (flow cytometry, proliferation assay (MTS assay)), M. tuberculosis and PM2.5 phagocytosis (microscopy), cytokine-producing cells (Enzyme-linked immune absorbent spot (ELISPOT)), and signalling pathway markers (western blot) were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from healthy, non-smoking, residents of Mexico City (n=35; 13 female, 22 male). In vivo-acquired PM burden in alveolar macrophages (AM) was measured by digital image analysis.Measurements and main resultsIn vitro exposure of AM to PM2.5 did not affect M. tuberculosis ...
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