scholarly journals In vitro and in vivo cardiac toxicity of flavored electronic nicotine delivery systems

2021 ◽  
Vol 320 (1) ◽  
pp. H133-H143
Author(s):  
Obada Abouassali ◽  
Mengmeng Chang ◽  
Bojjibabu Chidipi ◽  
Jose Luis Martinez ◽  
Michelle Reiser ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Cardiac Electrophysiology ◽  
Cardiac Toxicity ◽  
Delivery Systems ◽  
Cardiac Safety ◽  
Electronic Nicotine Delivery Systems ◽  
Nicotine Delivery

The use of electronic nicotine delivery systems (ENDS) is not harm free. It is not known whether ENDS negatively affect cardiac electrophysiological function. Our study in cell lines and in mice shows that ENDS can compromise cardiac electrophysiology, leading to action potential instability and inducible ventricular arrhythmias. Further investigations are necessary to assess the long-term cardiac safety profile of ENDS products in humans and to better understand how individual components of ENDS affect cardiac toxicity.

scholarly journals Vaping Perpetuates Cardiac Electrical Instability

2019 ◽  
Author(s):  
Obada Abouassali ◽  
Mengmeng Chang ◽  
Michelle Reiser ◽  
Manasa Kanithi ◽  
Ravi Soni ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Cardiac Toxicity ◽  
Optical Mapping ◽  
Cellular Respiration ◽  
Electrode Arrays ◽  
Tobacco Cigarette ◽  
Nicotine Delivery ◽  
Beating Frequency

ABSTRACTBackgroundTobacco cigarette smoking is on the decline, but the usage of electronic nicotine delivery systems (ENDS) is gaining popularity, specifically in the teen and young adult age groups. While the cardiac toxicity of tobacco cigarette smoking has been widely studied and is well established, the possible cardiac toxicity of ENDS products and their design characteristics, such as added flavorings, are largely underexplored. Vaping, a form of electronic nicotine delivery, uses “e-liquid” to generate “e-vapor”, a smoke-like aerosolized mixture of nicotine and flavors. Here, we tested the hypothesis that vaping results in cardiac electrophysiological instability and arrhythmogenesis. We thus investigated how e-liquids with different flavors affect cardiac in-vitro and in-vivo toxicity, in cell culture and in animals.MethodsThree e-liquids with vanilla, cinnamon or fruit flavors were studied. We quantified apoptosis and oxygen consumption rate in HL-1 cells cultured with e-vapors extracts. In human iPSC derived ventricular cardiomyocytes (hiPSC-CM) cultured with e-vapor extract, beating frequency and repolarization duration were measured using multiple electrode arrays (MEA). Mass spectrometry (GC-MS) was used to analyze the composition of the e-vapors. Telemetric ECGs were obtained in freely moving C57BL/6J mice exposed to vanilla flavored e-vapor for 10 weeks and heart rate variability was analyzed (HRV). In-vivo inducibility of ventricular tachycardia as well as optical mapping of voltage in isolated Langendorff-perfused hearts were also carried out.ResultsE-vapor caused a dose dependent increase in toxicity in Hl-1 myocytes and e-vapors containing vanilla and cinnamon flavorings, as indicated by GC-MS, were more toxic, and inhibited cellular respiration more than the fruit flavored e-vapor. In hiPSC-CM cultured with 25% cinnamon flavored e-vapor for 24 hours, beating frequency increased, and the field potential duration significantly increased compared to air control. Inhalation exposure to vanilla flavored e-vapor for 10 weeks caused significant effects on HRV. Additionally, inducible VT was significantly longer, and in optical mapping, the magnitude of ventricular action potential duration alternans was significantly larger in the exposed mice compared to controlConclusionThe widely popular flavored ENDS are not harm free, and they show potential toxicity to the heart, in-vitro, and in vivo. Further studies are needed to further assess their cardiac safety profile, and long-term health effects.

scholarly journals A scoping review of studies on the health impact of electronic nicotine delivery systems

2021 ◽  
Author(s):  
Cother Hajat ◽  
Emma Stein ◽  
Saran Shantikumar ◽  
Raymond Niaura ◽  
Pietro Ferrara ◽  
...  
Keyword(s):  
Mental Health ◽  
Scoping Review ◽  
Controlled Trial ◽  
Health Impact ◽  
Delivery Systems ◽  
Chronic Obstructive ◽  
Cross Sectional ◽  
Electronic Nicotine Delivery Systems ◽  
Nicotine Delivery

AbstractWe conducted a scoping review of studies on health outcomes from electronic nicotine delivery systems (ENDS). The objective was to identify, narratively synthesize, assess the strength and quality of evidence and critically appraise studies that have reported disease end points associated with the use of ENDS. We included published literature on the health impact of ENDS from 01/01/2015 until 01/02/2020 following the PRISMA guidelines using PubMed, Embase, Scopus and Google Scholar. The database search identified 755 studies, and other sources 265; 37 studies met final eligibility criteria. Levels of evidence included 24(65%) cross-sectional, one (2.7%) case–control and six (16%) case studies, four (11%) cohort studies, one (2.7%) randomized controlled trial (RCT) and one (2.7%) meta-analysis; 27(73%) studies reported only on harms, eight (22%) reported on benefits, two (2%) on benefits and harms. Quality ratings were poor in 20 (54%), fair in 9(24%) and good in 8(22%) of studies. In our review, ENDS was not shown to be causative for harmful cardiovascular disease (CVD) outcomes and shown to be beneficial for hypertensive patients. Switching from cigarettes to e-cigarettes resulted in reduced exacerbations of chronic obstructive pulmonary disease (COPD), with no evidence of long-term deterioration in lung function. Mental Health, cancer and mortality were not adequately studied to form any consensus. Our review has not demonstrated ENDS to be causative of harmful CVD outcomes; furthermore switching from cigarettes to e-cigarettes was associated with improved hypertensive control and reduced exacerbations of COPD, with no evidence of increased asthma risk or long-term respiratory harm. Mental health, cancer and mortality outcomes have not been adequately studied to form a conclusion. Overall, the findings of our review did not provide evidence to counter the consensus held by many that ENDS use is safer than the risks posed from smoking cigarettes.

scholarly journals Electronic Nicotine Delivery Systems (ENDS) and Their Relevance in Oral Health

Toxics ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 61 ◽  
Author(s):  
Gozde Isik Andrikopoulos ◽  
Konstantinos Farsalinos ◽  
Konstantinos Poulas
Keyword(s):  
Oral Health ◽  
Periodontal Diseases ◽  
Delivery Systems ◽  
Long Term Effects ◽  
Periodontal Health ◽  
Electronic Nicotine Delivery Systems ◽  
Nicotine Delivery ◽  
Gingival Cells ◽  
Oral Cells

The number and popularity of electronic nicotine delivery systems (ENDS) and especially e-cigarettes (e-cigs) have been increasing in the last decade. Although ENDS owe their popularity to excluding the harmful chemicals that are present in tobacco smoke, there is a debate whether they are safe, regulated, and as harmless as they are assumed to be and have potential unknown long-term effects. Involvement of cigarette smoking to the progression of periodontal diseases, other adverse oral health outcomes, and its detrimental effects to oral health are well-described. ENDS producer companies claim that these products can improve oral health by providing alternatives to smoking. However, the effect of e-cigs on oral health is not fully understood and is still debated among many scientists and clinicians. The number of studies addressing the potential toxic effect of ENDS or e-cig aerosol on oral cells is limited along with the clinical studies which are still preliminary, and their sample size is limited. The long-term effects of inhaled aerosols and the potential synergistic effect of the e-cigs components are not known. It is essential and of utmost importance to determine whether exposure to ENDS aerosol contributes to the progression of periodontal diseases and how it affects periodontal ligament and gingival cells which are believed to be its first targets. This review briefly summarizes the available evidence about the effects of e-cigs on periodontal health including several pathophysiological events, such as oxidative stress, DNA damage, inflammation, cellular senescence, dysregulated repair, and periodontal diseases.

scholarly journals Beliefs and Self-reported Practices of Health Care Professionals Regarding Electronic Nicotine Delivery Systems: A Mixed-Methods Systematic Review and Synthesis

2019 ◽  
Vol 22 (5) ◽  
pp. 619-629 ◽  
Author(s):  
Daniel A Erku ◽  
Coral E Gartner ◽  
Kylie Morphett ◽  
Kathryn J Steadman
Keyword(s):  
Health Care ◽  
Mixed Methods ◽  
Health Care Professionals ◽  
Delivery Systems ◽  
Potential Health ◽  
Electronic Nicotine Delivery Systems ◽  
Nicotine Delivery ◽  
Patient Health ◽  
Training And Support

Abstract Aims This review explores the (1) beliefs and attitudes of health care professionals (HCPs) toward electronic nicotine delivery systems (ENDS) including use as a smoking cessation aid and/or harm reduction, safety and regulation, and (2) the extent and content of patient–HCP communication about ENDS. Methods PubMed, Embase, CINAHL, and PsycINFO were searched to identify articles published since 2003. The Mixed Methods Appraisal Tool and Strengthening the Reporting of Observational Studies in Epidemiology checklists were used to assess the quality of studies. Thematic synthesis was used to analyze qualitative data. Results A total of 45 articles (32 quantitative, 12 qualitative, and 1 mixed) were included. There was wide variation regarding beliefs about the efficacy of ENDS as a cessation aid. Although the majority of HCPs believes that ENDS are safer than combustible cigarettes, they also have concern about the short and long-term safety of ENDS, uptake by adolescents, and the potential for ENDS to act as a “gateway” to smoking cigarettes. Beliefs about ENDS are influenced by media stories and experiences provided by patients. Although most HCPs do not proactively recommend ENDS, they are more likely to support ENDS use among patients with smoking related comorbidities, heavy smokers with previous unsuccessful quit attempts, or patients who express interest in trying them. Conclusions Overall, HCPs hold diverse views about the efficacy of ENDS and expressed wariness over their potential health effects. HCP endorsement of ENDS use seems to depend largely on patient health status, the presence of other competing risk factors and patient preferences. Implication Although evidence on safety and efficacy of ENDS is emerging, HCPs should be honest with their clients, stating that the long-term safety is not yet established but what is known is that they appear to be a lower risk alternative to cigarettes. Our review highlights a need for further training and support for HCPs regarding ENDS use, which would enable them to guide their clients in making evidence-based decisions.

scholarly journals Stealth-vaping: a new era of illicit substance misuse? a systematic review and meta-analysis of the prevalence of electronic nicotine delivery systems for the consumption of illicit substances

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S256-S257
Author(s):  
Tim Hicks ◽  
Rebecca Arrowsmith ◽  
Susannah Keill ◽  
Eleni Papadakou
Keyword(s):  
Random Effects ◽  
Delivery Systems ◽  
Significant Heterogeneity ◽  
Random Effects Model ◽  
Total Study Population ◽  
Electronic Nicotine Delivery Systems ◽  
Nicotine Delivery ◽  
Study Population ◽  
Illicit Substances

AimsTo estimate the prevalence of using Electronic Nicotine Delivery Systems (ENDS) for the consumption of illicit Substances (illegal under UK Law). We hypothesised that this is an increasingly common mode of delivery.BackgroundUsing ENDS to consume nicotine is increasing in popularity worldwide with a prevalence in the UK of 6% and in the USA 4%-6%. Existing studies have reported that people are switching to vaping because it is felt to be safer than smoking.However there is also emerging evidence that this mode of consumption is increasingly being used as it is discreet and much less easy to detect, hence sometimes referred to as stealth-vaping. This appears to be driving a switch to vaping to administer substances other than nicotine, notably, but not exclusively cannabis, including concentrated forms of Tetrahydrocannabinol (THC) and synthetic cannabinoids. Anecdotally this practice is known to be occurring in psychiatric inpatient settings.This is against a backdrop of the uncertain long-term effects of vaping and the emergence of case reports of the death of otherwise healthy young persons after using ENDS to consume cannabis.MethodSearch strategy: MEDLINE , EMBASE, Cochrane Database of Systematic Reviews, Grey Literature using Medical Subject Headings (MeSH), text words relating to vaping of drugs and hand searching journals.Statistical methods: Synthesis of data was performed using inverse variance with double arcsine transformation in MetaXL. Heterogeneity was assessed with the Cochran's Q and I2.ResultFrom 970 abstracts, 61 papers were selected for full text review, 18 met the inclusion criteria. The total study population for the outcome of ENDS nicotine users who also use ENDS for the consumption of illicit substances was 9098. There was significant heterogeneity with a random effects model prevalence of 17% (95%CI 7%-32%). The total study population for the outcome of cannabis users who use ENDS to consume cannabis was 52708. There was significant heterogeneity with a random effects model prevalence of 23% (95%CI 12%-37%).ConclusionThe use of ENDS to consume illicit substances is concerning as it appears to be relatively common practice. This was most notable in studies of existing cannabis users, younger people and medical marijuana users.Given the uncertainty of long term health consequences and poor understanding of sudden death in some users, this study highlights an emerging and substantial public health concern.Currently there is a paucity of primary studies to elucidate the impact on health.

Electronic Nicotine Delivery Systems Rejection Measure

2020 ◽  
Author(s):  
Scott R. Weaver ◽  
J. Wesley Heath ◽  
David L. Ashley ◽  
Jidong Huang ◽  
Terry F. Pechacek ◽  
...  
Keyword(s):  
Delivery Systems ◽  
Electronic Nicotine Delivery Systems ◽  
Nicotine Delivery

The depressing (negative) effect of oestradiol benzoate on the in vitro secretion of LH and FSH by the pituitary gland of the LRH-pretreated long-term ovariectomized rat changes into the augmentative (positive) effect after discontinuation of the LRH-pretreatment

1985 ◽  
Vol 110 (3) ◽  
pp. 329-337 ◽  
Author(s):  
G. A. Schuiling ◽  
H. Moes ◽  
T. R. Koiter
Keyword(s):  
Depressing Effect ◽  
Ovx Rats ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Negative Effect ◽  
Positive Effect ◽  
Perifusion System

Abstract. The effect of pretreatment in vivo with oestradiol benzoate on in vitro secretion of LH and FSH was studied in long-term ovariectomized (OVX) rats both at the end of a 5-day continuous in vivo pretreatment with LRH and 4-days after cessation of such LRH pretreatment. Rats were on day 0 sc implanted with osmotic minipumps which released LRH at the rate of 250 ng/h. Control rats were implanted with a piece of silicone elastomer with the dimensions of a minipump. On days 2 and 4 the rats were injected with either 3 μg EB or with oil. On day 5 part of the rats were decapitated and the in vitro autonomous (i.e. non-LRH-stimulated) and 'supra-maximally' LRHstimulated release of LH and FSH was studied using a perifusion system. From other rats the minipumps were removed on day 5 and perifusion was performed on day 9. On the 5th day of the in vivo LRH pretreatment the pituitary LH/FSH stores were partially depleted; the pituitaries of the EB-treated rats more so than those of the oil-injected rats. EB alone had no significant effect on the content of the pituitary LH- and FSH stores. On day 9, i.e. 4 days after removal of the minipumps, the pituitary LH and FSH contents had increased in both the oil- and the EB injected rats, but had not yet recovered to control values. In rats not subjected to the 5-days pretreatment with LRH EB had a positive effect on the supra-maximally LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. EB had no effect on the non-stimulated secretion of FSH. After 5 days of in vivo pretreatment with LRH only, the in vitro non-stimulated and supra-maximally LRH-stimulated secretion of both LH and FSH were strongly impaired, the effect correlating well with the LRH-induced depletion of the pituitary LH/FSH stores. In such LRH-pretreated rats EB had on day 5 a negative effect on the (already depressed) LRH-stimulated secretion of LH (not on that of FSH). EB had no effect on the non-stimulated LH/FSH secretion. It could be demonstrated that the negative effect of the combined LRH/EB pretreatment was mainly due to the depressing effect of this treatment on the pituitary LH and FSH stores: the effect of oestradiol on the pituitary LRH-responsiveness (release as related to pituitary gonadotrophin content) remained positive. In LRH-pretreated rats, however, this positive effect of EB was smaller than in rats not pretreated with LRH. Four days after removal of the minipumps there was again a positive effect of EB on the LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. The positive effect of EB on the pituitary LRH-responsiveness was as strong as in rats which had not been exposed to exogenous LRH. The non-stimulated secretion of FSH was again not affected by EB. The results demonstrate that the effect of EB on the oestrogen-sensitive components of gonadotrophin secretion consists of two components: an effect on the pituitary LRH-responsiveness proper, and an effect on the pituitary LH/FSH stores. The magnitude of the effect of EB on the LRH-responsiveness is LRH dependent: it is very weak (almost zero) in LRH-pretreated rats, but strong in rats not exposed to LRH as well as in rats of which the LRH-pretreatment was stopped 4 days previously. Similarly, the effect of EB on the pituitary LH and FSH stores is LRH-dependent: in the absence of LRH, EB has no influence on the contents of these stores, but EB can potentiate the depleting effect of LRH on the LH/FSH-stores. Also this effect disappear after cessation of the LRH-pretreatment.

THE ROLE OF POLYETHYLENIMINE IN ENHANCING PERFORMANCE OF GLUTAMATE BIOSENSORS

2018 ◽  
Vol 8 (3) ◽  
pp. 36-41
Author(s):  
Diep Do Thi Hong ◽  
Duong Le Phuoc ◽  
Hoai Nguyen Thi ◽  
Serra Pier Andrea ◽  
Rocchitta Gaia
Keyword(s):  
First Generation ◽  
Good Reproducibility ◽  
Complex Matrices ◽  
Long Term Stability ◽  
In Vitro Characterization ◽  
Glutamate Oxidase

Background: The first biosensor was constructed more than fifty years ago. It was composed of the biorecognition element and transducer. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples Glutamate is important biochemicals involved in energetic metabolism and neurotransmission. Therefore, biosensors requires the development a new approach exhibiting high sensibility, good reproducibility and longterm stability. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples. The aims of this work: To find out which concentration of polyethylenimine (PEI) exhibiting the most high sensibility, good reproducibility and long-term stability. Methods: We designed and developed glutamate biosensor using different concentration of PEI ranging from 0% to 5% at Day 1 and Day 8. Results: After Glutamate biosensors in-vitro characterization, several PEI concentrations, ranging from 0.5% to 1% seem to be the best in terms of VMAX, the KM; while PEI content ranging from 0.5% to 1% resulted stable, PEI 1% displayed an excellent stability. Conclusions: In the result, PEI 1% perfomed high sensibility, good stability and blocking interference. Furthermore, we expect to develop and characterize an implantable biosensor capable of detecting glutamate, glucose in vivo. Key words: Glutamate biosensors, PEi (Polyethylenimine) enhances glutamate oxidase, glutamate oxidase biosensors

Strategies to Protect Hematopoietic Stem Cells from Culture-Induced Stress Conditions

2020 ◽  
Vol 15 ◽  
Author(s):  
Fatima Aerts-Kaya
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Ex Vivo ◽  
Stress Conditions ◽  
Stress Factors ◽  
Hematopoietic Stem ◽  
Induced Stress

: In contrast to their almost unlimited potential for expansion in vivo and despite years of dedicated research and optimization of expansion protocols, the expansion of Hematopoietic Stem Cells (HSCs) in vitro remains remarkably limited. Increased understanding of the mechanisms that are involved in maintenance, expansion and differentiation of HSCs will enable the development of better protocols for expansion of HSCs. This will allow procurement of HSCs with long-term engraftment potential and a better understanding of the effects of the external influences in and on the hematopoietic niche that may affect HSC function. During collection and culture of HSCs, the cells are exposed to suboptimal conditions that may induce different levels of stress and ultimately affect their self-renewal, differentiation and long-term engraftment potential. Some of these stress factors include normoxia, oxidative stress, extra-physiologic oxygen shock/stress (EPHOSS), endoplasmic reticulum (ER) stress, replicative stress, and stress related to DNA damage. Coping with these stress factors may help reduce the negative effects of cell culture on HSC potential, provide a better understanding of the true impact of certain treatments in the absence of confounding stress factors. This may facilitate the development of better ex vivo expansion protocols of HSCs with long-term engraftment potential without induction of stem cell exhaustion by cellular senescence or loss of cell viability. This review summarizes some of available strategies that may be used to protect HSCs from culture-induced stress conditions.

scholarly journals An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marisa Nacke ◽  
Emma Sandilands ◽  
Konstantina Nikolatou ◽  
Álvaro Román-Fernández ◽  
Susan Mason ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Cellular Responses ◽  
Signalling Pathways ◽  
External Signal ◽  
Phosphoinositide Metabolism ◽  
Invasion And Metastasis ◽  
3 Dimensional

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.

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