High Concentrations Of Nicotine Research Articles

Improving the Quality of Low-grade Tobacco by Enzymatic Treatment and Co-fermentation with Yeast and Lactic Acid Bacteria.

Enzymatic treatment is a promising method to modulate the chemical composition, flavoring substances and to enhance the sensory quality of cigarettes. This study investigates the feasibility of enzymatic treatment in conjunction with co-fermentation with yeast and lactic acid bacteria to improve the quality of low-quality cigarettes. Amylase, flavourzyme, glucoamylase, protease, and their combinations were used for the enzymatic treatment of tobacco-sorghum by using the liquid-state fermentation method. The biochemical components and flavor substances of the fermented products were analyzed. The findings show that amylase and glucoamylase can effectively degrade starch into fermentable reducing sugars, facilitate microbial growth and proliferation, and significantly enhance the levels of flavoring alcohols and esters. Flavourzyme and glucoamylase, either individually or combined with amylase, achieved a more balanced distribution of flavor substances in the products. Additionally, flavourzyme was capable of increasing the content of guaiacol, solanesol, and 2-acetylpyrrole in the fermented products, thereby improving the richness and depth of the cigarette flavor. While the protease treatment group showed fewer flavor substances and higher nicotine content, which was detrimental to the quality of cigarettes. When integrating the fermentation products into low-quality cigarettes, flavourzyme and glucoamylase combined with amylase treatment received higher scores in sensory quality evaluations. This study provides a beneficial strategy for effectively improving the quality of low-quality cigarettes.

Cotinine influences the effect of high and low nicotine concentrations on planarian motility differently

Previous work from our laboratory showed that cotinine, a nicotine metabolite, reverses three nicotine-induced behavioral effects in freshwater planarians: motility decrease, seizure-like movements, and withdrawal-like behaviors. The present work explored whether cotinine, a nicotine metabolite, antagonized the nicotine-induced effects on planarian motility in a concentration-dependent manner. We found that nicotine decreased planarian motility at nicotine concentrations above 60 μM but increased planarian velocity at concentrations equal to or below 50 μM, in agreement with previous data. Cotinine did not affect planarian motility at a concentration range between 250 and 2750 μM. Furthermore, we found that cotinine alleviated the 100 μM nicotine-induced motility decrease in a concentration-dependent manner and reversed the low nicotine concentration motility increase, albeit in a concentration-independent manner. The apparent concentration-dependent alleviation of >60 μM nicotine-induced motility decrease by cotinine suggests an orthosteric relationship between nicotine and cotinine. On the other hand, the evident concentration-independent cotinine alleviation of the increase in motility induced by 50 μM nicotine suggests an allosteric relationship. Our data is consistent with the existing literature about the relationship between nicotine and cotinine in various models, reinforcing the case for the usefulness of the planarian model in pharmacological studies.

Ultrasonic Cigarettes: Chemicals and Cytotoxicity are Similar to Heated-Coil Pod-Style Electronic Cigarettes.

Our purpose was to test the hypothesis that ultrasonic cigarettes (u-cigarettes), which operate at relatively low temperatures, produce aerosols that are less harmful than heated-coil pod-style electronic cigarettes (e-cigarettes). The major chemicals in SURGE u-cigarette fluids and aerosols were quantified, their cytotoxicity and cellular effects were assessed, and a Margin of Exposure risk assessment was performed on chemicals in SURGE fluids. Four SURGE u-cigarette flavor variants ("Blueberry Ice," "Watermelon Ice," "Green Mint," and "Polar Mint") were evaluated. Flavor chemicals were quantified in fluids and aerosols using gas chromatography/mass spectrometry. Cytotoxicity and cell dynamics were assessed using the MTT assay, live-cell imaging, and fluorescence microscopy. WS-23 (a coolant) and total flavor chemical concentrations in SURGE were similar to e-cigarettes, while SURGE nicotine concentrations (13-19 mg/mL) were lower than many fourth generation e-cigarettes. Transfer efficiencies of dominant chemicals to aerosols in SURGE ranged from 44-100%. SURGE fluids and aerosols had four dominant flavor chemicals (>1 mg/mL). Toxic aldehydes were usually higher in SURGE aerosols than in SURGE fluids. SURGE fluids and aerosols had aldehyde concentrations significantly higher than pod-style e-cigarettes. Chemical constituents, solvent ratios, and aldehydes varied among SURGE flavor variants. SURGE fluids and aerosols inhibited cell growth and mitochondrial reductases, produced attenuated and round cells, and depolymerized actin filaments, effects that depended on pod flavor, chemical constituents, and concentration. The MOEs for nicotine, WS-23, and propylene glycol were <100 based on consumption of 1-2 SURGE u-cigarettes/day. Replacing the heating coil with a sonicator did not eliminate chemicals, including aldehydes, in aerosols or diminish toxicity in comparisons between SURGE and other e-cigarette pod products. The high concentrations of nicotine, WS-23, flavor chemicals, and aldehydes and the cytotoxicity of SURGE aerosols do not support the hypothesis that aerosols from u-cigarettes are less harmful than those from e-cigarettes.

Development and characterization of tobacco suspension cell chassis NBS-1

Plant synthetic biology has significant theoretical advantages in exploration and production of plant natural products. However, its contribution to the field of biosynthesis is currently limited due to the lack of efficient chassis systems and related enabling technologies. Synthetic biologists often avoid tobacco as a chassis system because of its long operation cycle, difficulties in genetic and metabolic modification, complex metabolism and purification background, nicotine toxicity, and challenges in accurately controlling for agricultural production. Nevertheless, the tobacco suspension cell chassis system offers a viable solution to these challenges. The objective of this research was to develop a tobacco suspension cell chassis with high scientific and industrial potential. This chassis should exhibit rapid growth, high biomass, excellent dispersion, high transformation efficiency, and minimal nicotine content. Nicotiana benthamiana, which has high applicability in molecular technology, was used to induce suspension cells. The induced suspension cells, named NBS-1, exhibited rapid growth, excellent dispersion, and high biomass, reaching a maximum biomass of 476.39 g/L (fresh weight), which was significantly higher than that of BY-2. The transformation efficiency of the widely utilized pEAQ-HT transient expression system in NBS-1 reached 81%, which was substantially elevated compared to BY-2. The metabolic characteristics and bias of BY-2 and NBS-1 were analyzed using transcriptome data. It was found that the gene expression of pathways related to biosynthesis of flavonoids and their derivatives in NBS-1 was significantly higher, while the pathways related to alkaloid biosynthesis were significantly lower compared to BY-2. These findings were further validated by the total content of flavonoid and alkaloid. In summary, our research demonstrates NBS-1 possesses minimal nicotine content and provides valuable guidance for selecting appropriate chassis for specific products. In conclusion, this study developed NBS-1, a tobacco suspension cell chassis with excellent growth and transformation, high flavonoid content and minimal nicotine content, which has important guiding significance for the development of tobacco suspension cell chassis.

Harm perceptions across vaping product features: An on-line cross-sectional survey of adults who smoke and/or vape in the United Kingdom.

Vaping products are diverse with a wide variety of features, and popular products change rapidly. This study examined the features and types of vaping products that people who smoke and/or vape perceive contribute to the health harms of vaping. This was a cross-sectional survey co-designed with adults who smoked/vaped and pre-registered. An on-line survey (November 2022) was used of a convenience sample of adults in the United Kingdom who smoked and/or vaped (n = 494). As primary outcomes, respondents were asked to select any of 15 vaping product features they perceived might have any effect on the health harms of vaping (for each: selected, not selected). Independent variables were smoking/vaping status (smoke and vape; vape, formerly smoked; vape, never regularly smoked; smoke, do not currently vape); relative vaping harm perceptions [less harmful than smoking (accurate), equally/more harmful than smoking or do not know/refused (other)]. Binary logistic regressions were used to compare outcomes by current vaping/smoking status and relative harm perceptions, adjusting for age and sex. Most people (54.7%) selected between one and three features. The most frequently selected were nicotine concentration (62.2%) and amount of e-liquid consumed (59.1%), followed by nicotine type (e.g. salt or freebase; 33.0%), source/purchase location (25.3%), flavours (24.7%), temperature to heat e-liquid (21.1%), heat produced by device (20.9%), e-liquid brand (20.9%), amount of emissions (18.6%), device type (e.g. disposable, pod, tank; 17.2%), material of tank (17.0%), power/wattage (13.0%), device brand (8.1%), device size (4.1%) and device weight (2.4%). Higher nicotine concentrations, more e-liquid and salt (versus freebase) nicotine were perceived to confer greater harms. Disposables were perceived as slightly more harmful than reusable devices. There were few differences by current vaping/smoking status and between those with accurate (versus other) harm perceptions of vaping relative to smoking (P > 0.05 for most contrasts, adjusting for age and sex). Certain features and types of vaping products [higher nicotine concentrations, more e-liquid consumed and salt (versus freebase) nicotine]were perceived to confer greater health harms among a sample of UK adults who smoked and/or vaped. Findings are consistent with pervasive misperceptions that nicotine is a major cause of harm, although e-liquid volume is likely to contribute to harms.

Dual Regulation of Nicotine on NLRP3 Inflammasome in Macrophages with the Involvement of Lysosomal Destabilization, ROS and α7nAChR.

Nicotine, the primary alkaloid in tobacco products, has been shown to have immunoregulatory function in at least 20 diseases. The biological mechanism of action of nicotine immunoregulation is complex, resulting in an improvement of some disease states and exacerbation of others. Given the central role of the NLRP3 inflammasome in macrophages among multiple inflammatory diseases, this study examined how nicotine alters NLRP3 inflammasome activation in macrophages. NLRP3 inflammasome activation was examined mechanistically in the context of different nicotine dosages. We show NLRP3 inflammasome activation, apoptosis-associated speck-like protein (ASC) expression, caspase-1 activity and subsequent IL-1β secretion were positively correlated with nicotine in a dose-dependent relationship, and destabilization of lysosomes and ROS production were also involved. At high concentrations of nicotine surpassing 0.25mM, NLRP3 inflammasome activity declined, along with increased expression of the anti-inflammatory Alpha7 nicotinic acetylcholine receptor (α7nAChR) and the inhibition of TLR4/NF-κB signaling. Consequently, high doses of nicotine also reduced ASC expression, caspase-1 activity and IL-1β secretion in macrophages. Collectively, these results suggest a dual regulatory function of nicotine on NLRP3 inflammasome activation in macrophages, that is involved with the pro-inflammatory effects of lysosomal destabilization and ROS production. We also show nicotine mediates anti-inflammatory effects by activating α7nAChR at high doses.

The impact of high nicotine concentrations on the viability and cardiac differentiation of mesenchymal stromal cells: a barrier to regenerative therapy for smokers.

Background: Current treatment methods are not successful in restoring the lost cardiomyocytes after injury. Stem cell-based strategies have attracted much attention in this regard. Smoking, as a strong cardiovascular risk factor, not only affects the cardiac cells adversely but also deteriorates the function of stem cells. Since mesenchymal stem cells (MSCs) are one of the popular candidates in cardiovascular disease (CVD) clinical trials, we investigated the impact of nicotine on the regenerative properties (viability and cardiac differentiation) of these cells. Methods: MSCs were isolated from rat bone marrow and characterized based on morphology, differentiation capability, and the expression of specific mesenchymal markers. The MTT assay was used to assess the viability of MSCs after being exposed to different concentrations of nicotine. Based on MTT findings and according to the concentration of nicotine in smokers' blood, the growth curve and population doubling time were investigated for eight consecutive days. Cells were treated with 5-azacytidine (an inducer of cardiac differentiation), and then the expressions of cardiac-specific markers were calculated by qPCR. Results: MSCs were spindle-shaped, capable of differentiating into adipocyte and osteocyte, and expressed CD73 and CD90. The viability of MSCs was reduced upon exposure to nicotine in a concentration- and time-dependent manner. The growth curve showed that nicotine reduced the proliferation of MSCs, and treated cells needed more time to double. In addition, the expressions of GATA4 and troponin were downregulated in nicotine-treated cells on day 3. However, these two cardiac markers were overexpressed on day 7. Conclusion: Nicotine decreased normal growth and reduced the expression of cardiac markers in MSCs. This aspect is of eminent importance to smokers with cardiovascular disease who are candidates for stem cell therapy.

Nicotine, Humectants, and Tobacco-Specific Nitrosamines (TSNAs) in IQOS Heated Tobacco Products (HTPs): A Cross-Country Study.

Heated Tobacco Products (HTPs) purport to reduce exposure to tobacco-related toxicants compared to combustible cigarettes. This cross-sectional study examined the content of nicotine, two humectants (propylene glycol (PG) and vegetable glycerin (VG)), and four tobacco-specific nitrosamines (TSNAs: NNN, NNK, NAT, and NAB) in the tobacco filler of a popular HTP brand (IQOS). Non-menthol and menthol IQOS sticks were purchased from nine countries between 2017 and 2020 and were classified into two versions ("Bold" and "Light") using Philip Morris's flavor descriptors. The average nicotine concentration was 4.7 ± 0.5 mg/stick, and the highest nicotine concentration was found in products from Japan (5.1 ± 0.2 mg/stick). VG was the dominant humectant found in all sticks, with an average concentration of (31.5 ± 2.3 mg/stick). NNN, NNK, and NAT were substantially higher in the "Bold" sticks than the "Light" sticks. Significant differences between countries for TSNAs were also observed: the NAT and NAB contents were the highest in the "Light" products from Canada (192.5 ± 24.1 and 22.9 ± 1.0 ng/stick, respectively); the NNK concentration was the highest in the "Bold" products from Poland (64.8 ± 7.9 ng/stick); and the highest NNN concentrations were observed in the "Bold" products from South Africa (488.9 ± 26.7 ng/stick). As NNN and NNK are known human carcinogens, and as humectants like PG and VG can degrade into toxic carbonyl compounds upon heating, monitoring the concentration of these chemicals in HTPs is important for protecting users' health and ensuring compliance with regulations.

Correlates of using E-cigarettes with high nicotine concentrations among U.S. adults who exclusively vape E-cigarettes or dual use with cigarettes

BackgroundIdentifying the correlates of using e-cigarettes with high nicotine concentrations in exclusive and dual-using vapers can elucidate which subpopulations might be most impacted by e-cigarette regulatory activities related to nicotine concentration. MethodsData are drawn from Wave 5 (December 2018-November 2019) of the Population Assessment of Tobacco and Health (PATH) study. Self-reported nicotine concentration was grouped as high (5.0 %+), moderate (1.8–4.9 %), low (0.1–1.7 %), 0 %, and “I don’t know.” Multivariable logistic regressions estimated associations of sociodemographic factors, tobacco use status, and e-cigarette use patterns of high nicotine concentration vs. other nicotine levels, stratified by current exclusive e-cigarette use and dual use of e-cigarettes and cigarettes. ResultsIn the study samples (exclusive e-cigarette use [n = 1,755], dual-use [n = 1,200]), higher proportions of exclusive e-cigarette users reported using high nicotine concentrations than dual users (18.3 % vs. 8.6 %). Among exclusive e-cigarette users, never vs. former smokers and daily (vs. someday) e-cigarette users were more likely to use high vs. low nicotine. In both exclusive and dual users, younger (vs. older) adults were more likely to report using high nicotine concentration e-cigarettes than most other nicotine levels. Current dual users who did vs. did not report using e-cigarettes to quit smoking had higher odds of using high vs. 0 % nicotine concentrations. ConclusionsHigh-nicotine e-cigarette use might be elevated in subpopulations that face greater risks for vaping (e.g., never smokers, young adults) than groups who benefit from the potential harm reduction. Regulatory restrictions on high-nicotine products may selectively affect some subgroups adversely impacted by vaping.

Poisoning with e-cigarette liquid (VPG Power Smoke Baze) - case report

Introduction and purpose: E-cigarettes have emerged as an alternative to traditional tobacco smoking. Toxicological studies have investigated the composition and potential toxicity of e-cigarette liquid components. While they are generally considered less harmful than combustible cigarettes, cases of poisoning associated with e-cigarette liquid ingestion or exposure have been reported.&#x0D; Brief description of the state of knowledge: Nicotine intoxication resulting from e-cigarette liquid ingestion can lead to a range of symptoms and complications, including cardiovascular effects, neurological symptoms, gastrointestinal disturbances, respiratory issues, and even death. This report presents a case of a 58-year-old woman hospitalized in the Toxicology and Cardiology Department due to poisoning with e-cigarette liquid.&#x0D; Conclusions: Accidental or intentional ingestion and/or injection of e-liquid is becoming a new emerging challenge for Emergency Medicine, mainly because of the easy accessibility of advertisements and the sales of e-cigarettes online, and the high nicotine concentration in e-liquids. It is important to report instances of e-liquid-related nicotine intoxication in order to improve the legal restrictions on the sale of e-liquid.

Association of Smoke and Nicotine Product Consumption With Sensorineural Hearing Loss: A Population-Level Analysis.

To test the hypothesis that use of cigarettes or other products with either cigarette-like smoke profile or high nicotine content by young populations increases the odds of developing sensorineural hearing loss (SNHL). Retrospective cohort study. TriNetX US Collaborative Network (2003-2022). Approximately 3.6 million patients at least 18 years old. None. The primary outcome of interest was diagnosis of SNHL, defined using medical billing codes (International Classification of Diseases, Tenth Revision, Current Procedural Terminology, etc.). Cohort inclusion criteria included electronic health record entry after 2003, age 18 to 54 or 55+ years at index, and status of cigarette, noncigarette nicotine, or cannabis use. Covariates were controlled via 1:1 propensity score matching for SNHL-related conditions, including diabetes mellitus and ischemic diseases. Odds for developing SNHL were calculated against control subjects aged 18 to 54 years who have no record of nicotine/cannabis use. Odds for developing SNHL are higher for people 18 to 54 years old who use any nicotine product (odds ratio [95% confidence interval], 5.91 [5.71-6.13]), cigarettes only (4.00 [3.69-4.33]), chewing tobacco only (9.04 [7.09-11.63]), or cannabis only (3.99 [3.60-4.44]) compared with control. People 55+ years old who use no products also showed increased odds for SNHL (4.73 [4.63-4.85]). Both nicotine and smoke exposure seem to be strongly associated with increased odds for developing SNHL, with chewing tobacco having the strongest association.

Ovarian toxicity of e-cigarette liquids: Effects of components and high and low nicotine concentration e-cigarette liquid in vitro.

Electronic cigarette use has become increasingly popular, with potential consequences for reproductive health. We aimed to investigate the effects of different components of e-liquid on the ovary and compare the impact of low nicotine concentration e-liquids (LN e-liquids) and high nicotine concentration e-liquids (HN e-liquids) on ovarian toxicity. A total of 378 rat ovaries were divided into seven groups, including control (no intervention), nicotine (0.05 mg/mL), flavoring (0.25 μL/mL), propylene glycol (PG) (2.5 μL/mL), vegetable glycerin (VG) (2.0 μL/mL), LN e-liquid (0.05 mg nicotine + 0.25 μL flavoring + 2.5 μL PG + 2.0 μL VG + 0.25 μL distilled water/mL medium) and HN e-liquid groups (0.05 mg nicotine + 0.05 μL flavoring + 0.5 μL PG + 0.4 μL VG + 0.05 μL distilled water/mL medium). After three hours of in vitro culture, ovarian morphology, oxidation levels [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA)], and apoptosis levels [factor related apoptosis (Fas), Cyt-c, Caspase-9, Caspase-3] were analyzed. Our findings indicate that nicotine has limited impact on the ovary, while flavoring, PG, and VG all cause ovarian damage including morphological damage, disruption of oxidative balance and promotion of apoptosis, with VG having the most significant effect. Moreover, LN e-liquids may lead to more severe ovarian damage than HN e-liquids at an equal intake of total nicotine. Our study highlights that in e-liquid formula, nicotine has a limited effect on the ovaries, but flavoring, PG, and VG all cause damage to the ovaries, with VG the most damaging. At a consistent level of total nicotine intake, e-liquids with low nicotine concentrations cause more damage to the ovaries than those with high nicotine concentrations. These findings contribute to a better understanding of the impact of e-liquids on ovarian health and have important implications for public health policy.

Effects of E-Cigarette Vapor Smoke on Pulmonary Alveoli in Rattus norvegicus Lungs

Introduction: Vapor is considered a safer alternative to tobacco cigarettes because the high nicotine content is less. However, vapor still contains substances that are classified as toxic to humans. Short-term exposure to vapors from liquids can induce an inflammatory response in the lungs and cause oxidative stress. This study aimed to determine the effects of e-cigarette vapor smoke on pulmonary alveoli in Rattus norvegicus lungs. Methods: This was an experimental study on 32 adult male Rattus norvegicus rats. They were divided into two groups exposed to nicotine-containing vapor smoke two times a day for one and three months, respectively, and one group as control. After vapor exposure, the lung tissues of the rats were taken and then subjected to histopathological examination under a microscope. Results: After exposure for one month, epithelial and endothelial cells degenerated, characterized by a decrease in collagen and elastin fibers in the extracellular matrix. For three months, there were changes, the alveolar membrane had no nucleus, the surrounding endothelial cells were not visible due to damage to the extracellular matrix, the alveolar lumen had widened, causing edema in the lumen of the alveoli, and the alveoli wall was destroyed. Therefore, the connection between the alveoli was stretched. Conclusion: This study found that short-term exposure to nicotine vapor causes damage to the alveoli membrane.

Bigger, stronger and cheaper: growth in e-cigarette market driven by disposable devices with more e-liquid, higher nicotine concentration and declining prices

ObjectiveGiven the evolving changes in the disposable e-cigarette market, we explore patterns of sales in the USA by e-liquid volume capacity, nicotine strength and real sales-weighted average prices by both...

Evaluation of the Effects of e-Cigarette Aerosol Extracts and Tobacco Cigarette Smoke Extracts on RAW264.7 Cells.

With the advancement of society, electronic cigarettes (e-cigarettes) have gained popularity among a growing number of individuals. While numerous toxicological studies have suggested that e-cigarettes are a safer alternative to traditional cigarettes, there is also a body of literature presenting contrasting findings. This in vitro study aimed to compare the effects of e-cigarettes and tobacco cigarettes (t-cigarettes) on RAW264.7 cells by using four e-cigarette aerosol extracts (ECA) and cigarette smoking extracts (CS) containing different nicotine concentrations. The results revealed that low concentration of nicotine in CS as well as in ECA with grape, watermelon, and cola flavors could promote cell viability. Conversely, high nicotine concentration in CS and ECA with four flavors decreased cell viability. Furthermore, our study demonstrated that CS significantly reduced the phagocytic capability of RAW264.7 cells and increased the levels of inflammatory cytokines (IL-6, TNF-α, and IL-1β) and reactive oxygen species (ROS) compared to ECA. Overall, our findings indicate all four e-cigarettes induced less cytotoxicity to RAW264.7 cells and might be safer than t-cigarettes.

Effects of the multi-stress-resistant strain Zygosaccharomyces parabailii MC-5K3 bioaugmentation on microbial communities and metabolomics in tobacco waste extract.

Industrial tobacco waste was mainly treated via a reconstituted tobacco process using the paper-making method, which involves aqueous concentrated tobacco waste extract (cTWE) fermentation (aging). The fermentation was done to improve the quality of reconstituted tobacco. However, cTWE is a multi-stress environment that is characterized by low pH (about 4), as well as high sugar (above 150g/L) and nicotine (above 15g/L) content. In this study, a specific selection strategy was used to successfully isolate multi-stress-resistant bacterial or fungal strains, that exhibited positive effects on cTWE fermentation, thereby improving the quality of final products. A potential strain Zygosaccharomyces parabailii MC-5K3 was used for the bioaugmentation of cTWE fermentation and it significantly influenced the microbial diversity of the fermented cTWE. Zygosaccharomyces was observed to be the only dominant fungal genus instead of some pathogenic bacterial genera, with an abundance of over 95% after four days, and still more than 80% after a week. Meanwhile, metabolomics profiling showed significant concentration decrease with regard to some flavor-improving relative metabolites, such as 3-hydroxybenzoic acid (log2FC = -5.25) and sorbitol (log2FC = -5.54). This finding is extrapolated to be the key influence factor on the quality of the fermented cTWE. The correlation analysis also showed that the alterations in microbial diversity in the fermented cTWE led to some important differential metabolite changes, which finally improved various properties of tobacco products.

Chronic Inhalation of Pod-based e-cigarette Aerosols on Inflammatory Biomarkers in the Central Nervous and Peripheral Systems

Electronic cigarettes (e-cigs) use has been dramatically increased recently, especially among youths. In this study, we evaluated the effect of one- and three-months continuous exposure to e-cig vapor (JUUL pods), containing high nicotine concentration, on the expression of glutamate receptors and transporters and mainly the associated neuroinflammatory markers in drug reward brain regions such as nucleus accumbens (NAc) core (NAc-core), NAc shell (NAc-shell) and hippocampus (HIP) in female C57BL/6 mice. We revealed that three months’ exposure to mint or mango flavored-JUUL (containing 5% nicotine, 59 mg/ml) induced upregulation in metabotropic glutamate receptor 1 (mGluR1) and postsynaptic density protein 95 (phosphorylated and total PSD95) expression, and downregulation of mGluR5 and glutamate transporter 1 (GLT-1) in the NAc-shell. Three months’ exposure to JUUL induced upregulation of mGluR5 and GLT-1 expression in the HIPP. We further revealed that mice exposed to JUUL Mango and JUUL Mint for one month had significantly increased TNF-α expression in the NAc-core and NAc-shell, with elevation in IL-1β as well. NAc-shell also showed significantly increased levels of IL-6 and HMGB-1 for both flavors. There were significantly increased levels of TNF-α in the NAc-core and NAc-shell for both Mint- and Mango-exposed JUUL mice for three months. NAc-shell also showed significantly increased levels of IL-1β, IL-6, HMGB-1, and RAGE after three months of JULL exposure, while the hippocampus showed significantly decreased levels of HMGB-1 for both flavors. These findings demonstrated that exposure to e-cig vapor containing high nicotine concentrations induced differential effects on glutamatergic system as well as induction of proinflammatory markers in the brain.

Self-poisoning by E-cigarette and E-liquids: National Reports to French Poison Control Centers from July 2019 to December 2020: VIGIlance and VAPE: The VIGIVAPE Study.

Exposure to e-cigarette liquids, whether intentional or accidental, might lead to adverse events. This study aimed to describe the prevalence and characteristics of exposures to e-liquids reported to French Poison Control Centers. All e-liquids exposure cases reported to French Poison Control Centers from July 1, 2019, to December 31, 2020, were reviewed. Information was collected about the patient's characteristics, exposure circumstances, management and outcome. About 919 cases of exposure to e-liquids were reported. Ages ranged from one month to 89 years, with a mean age of 16.6 ± 18.6 years and a median age of 4 years. The highest number of exposures-50.7%-concerned infants (0-4 years), 3.1% children (5-11 years), 5.9% adolescents (12-17 years), and 40.1% of cases concerned adults. The majority of cases were accidental (95.0%). Intentional exposures (4.9%) were mainly observed in patients older than 12 years of age (P < 0.001). The route of exposure was ingestion in 73.7% of the cases. A total of 455 exposures showed no symptoms or signs related to poisoning. High nicotine concentration in e-liquids was associated with an increase in hospital management (Odds-ratio from 1.77 to 2.60). Involuntary exposures to e-liquids occurred more often in children under the age of five, mainly by ingestion. Unlike intentional ingestions, unintentional ingestions rarely resulted in severe adverse events. These findings highlight the importance of ongoing surveillance to prevent such exposures and associated injuries, emphasizing the need for effective regulation of these products.

E-cigarette Unit Sales by Product and Flavor Type, and Top-Selling Brands, United States, 2020-2022.

E-cigarette products, related policies, and use patterns change rapidly. In the United States, the prevalence of e-cigarette use is markedly higher among youths and young adults than it is among adults overall. In 2021, 4.5% of all adults aged ≥18 years (an estimated 11.1 million) and 11.0% of young adults aged 18-24 years (an estimated 3.1 million) currently (≥1 day during the previous 30 days) used e-cigarettes; during 2022, 14.1% of high school students (an estimated 2.14 million) currently used e-cigarettes (1,2). E-cigarettes often contain high concentrations of nicotine. Nicotine is highly addictive and can harm the adolescent brain, which continues to develop through approximately age 25 years (3). Since 2020, the availability of e-cigarette products has changed in response to multiple factors, including local and state policies to address flavored e-cigarette sales, actions undertaken by the Food and Drug Administration (FDA), COVID-19-related closures, and global supply chain disruptions. To assess trends in unit sales of e-cigarettes in the United States, by product and flavor, and top-selling brands, the CDC Foundation, Truth Initiative,* and CDC analyzed retail scanner data during January 26, 2020-December 25, 2022, from Information Resources, Inc. (IRI), a U.S. data analytics and market research company. Overall, unit sales increased by 46.6% during the study period. The unit share of menthol-flavored product sales remained relatively stable during this period, whereas nonmenthol flavor unit shares changed. During January 26, 2020-December 25, 2022, unit shares of tobacco-flavored and mint-flavored products decreased (from 28.4% to 20.1% and from 10.1% to 5.9%, respectively), whereas shares of other flavor sales increased (from 29.2% to 41.3%). In addition, during January 2020-December 2022, unit shares of prefilled cartridges decreased from 75.2% to 48.0%, and disposable e-cigarette unit share increased from 24.7% to 51.8% of total unit sales. The five top-selling e-cigarette brands for the 4-week period ending December 25, 2022, were Vuse, JUUL, Elf Bar, NJOY, and Breeze Smoke. Analysis of information on e-cigarette retail sales can guide strategies to prevent youth access to and use of e-cigarettes, including restrictions on flavored tobacco products (4).

Sensory appeal and puffing intensity of e-cigarette use: Influence of nicotine salts versus free-base nicotine in e-liquids

BackgroundIn the US, nicotine salts (with protonated nicotine instead of free-based nicotine) have been reported to lower the harshness and bitterness of e-cigarette aerosols, making it easier to inhale high levels of nicotine. This study aimed to determine whether nicotine salts also increase sensory appeal at lower concentrations (< 20mg/mL). Moreover, and novel, inhalation intensity of both types of e-liquids was compared. MethodsIn a randomized, double-blinded, within-participants design, healthy adults who use e-cigarettes (n=68) vaped tobacco-flavored e-liquids containing 12mg/mL of free-based nicotine or nicotine salt ad libitum, using their own device, during two online sessions (June-July 2021, Utrecht, The Netherlands). The sensory parameters perceived liking, nicotine intensity, harshness, and pleasantness were rated on a 100-unit visual analog scale. The intensity of use was determined by the recorded puff number, duration and interval. ResultsTest scores on appeal, harshness and puffing behavior parameters showed no significant differences between the nicotine salt and the free-base condition. The average inhalation time was 2.5seconds. Additional analyses found no significant effect of liquid order, age, gender, smoking status, vaping frequency and familiarity with nicotine salts. Significant positive correlations were found between the sensory parameters except for harshness. ConclusionsContrary to a previous study that used higher nicotine concentrations and standardized puffing conditions in a laboratory setting, we did not observe the effects of nicotine salts on sensory appeal in our real-life study paradigm. Moreover, we did not see effects on study parameters related to puffing intensity.