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Talanta Jun 2024Tobacco-specific alkaloids and nitrosamines are important biomarkers for the estimation of tobacco use and human exposure to tobacco-specific nitrosamines that can be...
Tobacco-specific alkaloids and nitrosamines are important biomarkers for the estimation of tobacco use and human exposure to tobacco-specific nitrosamines that can be monitored by wastewater analysis. Thus far their analysis has used solid phase extraction, which is costly and time-consuming. In this study, we developed a direct injection liquid chromatography-tandem mass spectrometry method for the quantification of two tobacco-specific alkaloids and five nitrosamines in wastewater. The method achieved excellent linearity (R > 0.99) for all analytes, with calibration ranging from 0.10 to 800 ng/L. Method limits of detection and quantification were 0.17 ng/L (N-nitrosonornicotine, NNN) and 1.0 ng/L (N-nitrosoanatabine (NAT) and NNN), with acceptable accuracy (100 % ± 20 %) and precision (± 15 %). Analyte loss during filtration was < 15 %, and the relative matrix effect was < 10 %. The method was applied to 43 pooled wastewater samples collected from three wastewater treatment plants in Australia between 2017 and 2021. Anabasine and anatabine were detected in all samples at concentrations of 5.0 - 33 ng/L and 12 - 41 ng/L, respectively. Three of the five tobacco-specific nitrosamines (NAT, NNN, and (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL)) were detected, in < 50 % of the wastewater samples, with concentrations nearly ten times lower than the tobacco alkaloids (< 1.0 - 6.2 ng/L). In-sewer stability of the nitrosamines was also assessed in this study, with four (NAT, NNAL, NNN, and N-nitrosoanabasine (NAB)) being stable (i.e. < 20 % transformation over 12 h in both control reactor (CR) and rising main reactor (RM) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) being moderately stable (< 40 % loss over 12 h in RM). This direct injection method provides a high-throughput approach in simultaneous investigation of tobacco use and assessment of public exposure to tobacco-specific nitrosamines.
PubMed: 38876037
DOI: 10.1016/j.talanta.2024.126401 -
Frontiers in Plant Science 2023Cigars are developing rapidly around the world, but the content characteristics of aroma precursors and their contribution to sensory perception have not been fully...
Cigars are developing rapidly around the world, but the content characteristics of aroma precursors and their contribution to sensory perception have not been fully elucidated. In this study, 69 aroma precursors from 61 tobaccos of different parts and origins were systematically determined, and the sensory characteristics of middle leaves from different origins and their correlation with aroma precursors were evaluated. The results showed that tobacco parts mainly affected amino acid content, and contents of nicotine, oxalic acid, malic acid, isovaleric acid, cystine, glutarnine, glycine, isoleucine, glutamicacid, asparticacid, and fructose-proline were significantly changed. Tobacco origins mainly influenced the contents of amino acids, polyacids and high fatty acids, and sugar alcohols, and significantly affected the contents of myosmine, anabasine, nonanoic acid, propanetriol, mannitol, mannose, glucose, alanine, arginine, glutarnine, glutamicacid, histidine, serine, threonine, tryptophan, fructose-alanine, and fructose-asparagine. The flavor characteristics were prominent by wood aroma, and the style and quality characteristics varied greatly among different origins of middle leaves. There were 34, 21, and 22 aroma precursors with high correlations with flavor, style, and quality characteristics. This study provides support for regulating the content and coordination of aroma precursors in different tobacco parts and origins to improve sensory characteristics.
PubMed: 38192690
DOI: 10.3389/fpls.2023.1264739 -
Water Research Feb 2024Previous wastewater-based epidemiology (WBE) studies have reported decreasing trends of nicotine and tobacco use in Australia before 2017, but there is concern that...
Previous wastewater-based epidemiology (WBE) studies have reported decreasing trends of nicotine and tobacco use in Australia before 2017, but there is concern that increasing illicit use of nicotine in vaping products and illicit tobacco could reverse this progress. This study aimed to assess temporal trends of nicotine consumption and specifically tobacco consumption via wastewater analysis in a population in Australia between 2013 and 2021. One week of daily wastewater samples were analyzed every two months from February 2013 to December 2021 in a regional city serving ∼100,000 people. A total of 340 daily samples were analyzed for anabasine (tobacco specific biomarker) and nicotine metabolites, cotinine and hydroxycotinine, using direct injection method by liquid chromatography with tandem mass spectrometry. Daily consumption estimates were calculated from daily flow data, population estimates and previously reported excretion factors. Linear spline regression was performed to identify periods when significant change of slopes occurred and to evaluate the temporal trends. Tobacco use monitored using anabasine as a biomarker, showed a decreasing trend over the whole period with a higher rate of decrease during the first two years (2013-2014, 21 % decrease) compared to the later 7 years (2015-2021, 10 % decrease). Nicotine use, monitored using cotinine and hydroxycotinine, showed a downward trend between 2013 and 2018 (2013-2014: 18 % decrease, p < 0.05; 2015-2016: 6 % increase, p = 0.48; Feb-Dec 2017: 15 % decrease, p = 0.39) followed by a significant increase from 2018 to 2021 (40 % increase, p < 0.001). This finding suggests the increasing use of non-tobacco nicotine-based products. Additionally, the tobacco use estimate by wastewater analysis was higher than the tobacco sales data, which suggests the use of illicit tobacco in the catchment.
Topics: Humans; Nicotine; Cotinine; Wastewater; Anabasine; Queensland; Australia; Biomarkers
PubMed: 38154341
DOI: 10.1016/j.watres.2023.121040 -
Molecules (Basel, Switzerland) Nov 2023Measurement of multiple nicotine metabolites and total nicotine equivalents (TNE) might be a more reliable strategy for tobacco exposure verification than measuring...
Simultaneous Measurement and Distribution Analysis of Urinary Nicotine, Cotinine, Trans-3'-Hydroxycotinine, Nornicotine, Anabasine, and Total Nicotine Equivalents in a Large Korean Population.
Measurement of multiple nicotine metabolites and total nicotine equivalents (TNE) might be a more reliable strategy for tobacco exposure verification than measuring single urinary cotinine alone. We simultaneously measured nicotine, cotinine, 3-OH cotinine, nornicotine, and anabasine using 19,874 urine samples collected from the Korean National Health and Nutrition Examination Survey. Of all samples, 18.6% were positive for cotinine, 17.4% for nicotine, 17.3% for nornicotine, 17.6% for 3-OH cotinine, and 13.2% for anabasine. Of the cotinine negative samples, less than 0.3% were positive for all nicotine metabolites, but not for anabasine (5.7%). The agreement of the classification of smoking status by cotinine combined with nicotine metabolites was 0.982-0.994 (Cohen's kappa). TNE3 (the molar sum of urinary nicotine, cotinine, and 3-OH cotinine) was most strongly correlated with cotinine compared to the other nicotine metabolites; however, anabasine was less strongly correlated with other biomarkers. Among anabasine-positive samples, 30% were negative for nicotine or its metabolites, and 25% were undetectable. Our study shows that the single measurement of urinary cotinine is simple and has a comparable classification of smoking status to differentiate between current smokers and non-smokers relative to the measurement of multiple nicotine metabolites. However, measurement of multiple nicotine metabolites and TNE3 could be useful for monitoring exposure to low-level or secondhand smoke exposure and for determining individual differences in nicotine metabolism. Geometric or cultural factors should be considered for the differentiation of tobacco use from patients with nicotine replacement therapy by anabasine.
Topics: Humans; Nicotine; Cotinine; Anabasine; Smoking Cessation; Nutrition Surveys; Alkaloids; Tobacco Use Cessation Devices; Biomarkers; Republic of Korea
PubMed: 38067415
DOI: 10.3390/molecules28237685 -
JAMA Network Open Jun 2023Adapting to different smoking cessation medications when an individual has not stopped smoking has shown promise, but efficacy has not been tested in racial and ethnic... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Adapting to different smoking cessation medications when an individual has not stopped smoking has shown promise, but efficacy has not been tested in racial and ethnic minority individuals who smoke and tend to have less success in quitting and bear a disproportionate share of tobacco-related morbidity and mortality.
OBJECTIVE
To evaluate efficacy of multiple smoking cessation pharmacotherapy adaptations based on treatment response in Black adults who smoke daily.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial of adapted therapy (ADT) or enhanced usual care (UC) included non-Hispanic Black adults who smoke and was conducted from May 2019 to January 2022 at a federally qualified health center in Kansas City, Missouri. Data analysis took place from March 2022 to January 2023.
INTERVENTIONS
Both groups received 18 weeks of pharmacotherapy with long-term follow-up through week 26. The ADT group consisted of 196 individuals who received a nicotine patch (NP) and up to 2 pharmacotherapy adaptations, with a first switch to varenicline at week 2 and, if needed, a second switch to bupropion plus NP (bupropion + NP) based on carbon monoxide (CO)-verified smoking status (CO ≥6 ppm) at week 6. The UC group consisted of 196 individuals who received NP throughout the duration of treatment.
MAIN OUTCOMES AND MEASURES
Anabasine-verified and anatabine-verified point-prevalence abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points). The χ2 test was used to compare verified abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points) between ADT and UC. A post hoc sensitivity analysis of smoking abstinence at week 12 was performed with multiple imputation using a monotone logistic regression with treatment and gender as covariates to impute the missing data.
RESULTS
Among 392 participants who were enrolled (mean [SD] age, 53 [11.6] years; 224 [57%] female; 186 [47%] ≤ 100% federal poverty level; mean [SD] 13 [12.4] cigarettes per day), 324 (83%) completed the trial. Overall, 196 individuals were randomized to each study group. Using intent-to-treat and imputing missing data as participants who smoke, verified 7-day abstinence was not significantly different by treatment group at 12 weeks (ADT: 34 of 196 [17.4%]; UC: 23 of 196 [11.7%]; odds ratio [OR], 1.58; 95% CI, 0.89-2.80; P = .12), 18 weeks (ADT: 32 of 196 [16.3%]; UC: 31 of 196 [15.8%]; OR, 1.04; 95% CI, 0.61-1.78; P = .89), and 26 weeks (ADT: 24 of 196 [12.2%]; UC: 26 of 196 [13.3%]; OR, 0.91; 95% CI, 0.50-1.65; P = .76). Of the ADT participants who received pharmacotherapy adaptations (135/188 [71.8%]), 11 of 135 (8.1%) were abstinent at week 12. Controlling for treatment, individuals who responded to treatment and had CO-verified abstinence at week 2 had 4.6 times greater odds of being abstinent at week 12 (37 of 129 [28.7%] abstinence) than those who did not respond to treatment (19 of 245 [7.8%] abstinence; OR; 4.6; 95% CI, 2.5-8.6; P < .001).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of adapted vs standard of care pharmacotherapy, adaptation to varenicline and/or bupropion + NP after failure of NP monotherapy did not significantly improve abstinence rates for Black adults who smoke relative to those who continued treatment with NP. Those who achieved abstinence in the first 2 weeks of the study were significantly more likely to achieve later abstinence, highlighting early treatment response as an important area for preemptive intervention.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03897439.
Topics: Adult; Humans; Female; Middle Aged; Male; Smoking Cessation; Varenicline; Bupropion; Ethnicity; Minority Groups; Nicotine; Smoking
PubMed: 37338906
DOI: 10.1001/jamanetworkopen.2023.17895 -
Journal of Ethnopharmacology Dec 2023Crossbow-medicine needle therapy (microneedle roller combined with crossbow-medicine) is one of the external treatment methods of Miao Medicine in China. It is a way of...
Effect of microneedle roller on promoting transdermal absorption of crossbow-medicine liquid via transdermal administration of Traditional Chinese Medicine and the safety of crossbow-medicine needle therapy: An experimental study.
ETHNOPHARMACOLOGY RELEVANCE
Crossbow-medicine needle therapy (microneedle roller combined with crossbow-medicine) is one of the external treatment methods of Miao Medicine in China. It is a way of combining acupuncture with Chinese herbal medicine, which is widely used in clinical treatment of pain.
AIM OF THE STUDY
To observe the transdermal absorption promoting effect of microneedle roller via transdermal administration, and to discuss the transdermal absorption characteristics and the safety of crossbow-medicine needle therapy.
METHODS
Based on the determination of the content of the main components of crossbow-medicine prescription in our previous research, the present experiment was conducted in-vitro and in-vivo experiments and the skin of rats was used as the penetration barrier. For in-vitro experiment, the modified Franz diffusion cell method was used to determine the transdermal absorption rate and 24h cumulative transdermal absorption amount of the active ingredients of crossbow-medicine liquid. For in-vivo experiment, tissue homogenization was applied to compare the skin retention amount and plasma concentration of crossbow-medicine liquid absorbed at different time points via the aforementioned two modes of administration. Furthermore, the effect of crossbow-medicine needle on the morphological structure of rat skin stratum corneum was detected by hematoxylin-eosin (HE) staining. The safety of crossbow-medicine needle therapy was evaluated according to the scoring criteria of the skin irritation test.
RESULTS
1. In-vitro experiment: In the microneedle-roller group and crossbow-medicine liquid application group, the effect of transdermal delivery was identified in all the four ingredients of anabasine, chlorogenic acid, mesaconitine and hypaconitine. The 24h cumulative transdermal absorption amount and transdermal absorption rate of each ingredient in microneedle-roller group were significantly higher than those in crossbow-medicine liquid application group (all P < 0.05). 2. In-vivo experiment: Both microneedle-roller and crossbow-medicine liquid application could promote the transdermal absorption of the active ingredients of the drug in the skin and retain in the skin structure. After 8h of administration, the total retention amount of anabasine, chlorogenic acid, mesaconitine and hypaconitine in the skin of rats in the former group was significantly higher than that in the latter group (all P < 0.05). 3. HE staining: In the blank group, the stratum corneum showed an evenly zonal distribution on the active epidermis, and had a close connection with the epidermis, without exfoliation or cell dissociation of the stratum corneum. The crossbow-medicine liquid group had a relatively complete stratum corneum, with a small proportion of exfoliation or cell dissociation, loose arrangement and loose connection with the epidermis. In the microneedle-roller group, the skin had pore channels, and the stratum corneum was loose and exfoliated, which showed zonal distribution in a free state and a high degree of separation. The crossbow-medicine needle group had loose the stratum corneum, broken and exfoliated, which was separated from the active epidermis and showed zonal distribution in a free state. 4.
SAFETY
No obvious erythema, edema and skin protuberance were observed in the skin of rats treated with microneedle roller, crossbow-medicine liquid and crossbow-medicine needle. Additionally, the skin irritative response score was 0.
CONCLUSION
Microneedle roller can promote the transdermal absorption of crossbow-medicine liquid, and crossbow-medicine needle therapy has good safety.
Topics: Rats; Animals; Skin Absorption; Administration, Cutaneous; Medicine, Chinese Traditional; Anabasine; Chlorogenic Acid; Skin; Needles
PubMed: 37295573
DOI: 10.1016/j.jep.2023.116751 -
Metabolites Apr 2023Alkaloids are the most diversified nitrogen-containing secondary metabolites, having antioxidant and antimicrobial properties, and are extensively used in... (Review)
Review
Alkaloids are the most diversified nitrogen-containing secondary metabolites, having antioxidant and antimicrobial properties, and are extensively used in pharmaceuticals to treat different types of cancer. Nicotiana serves as a reservoir of anti-cancer alkaloids and is also used as a model plant for the de novo synthesis of various anti-cancer molecules through genetic engineering. Up to 4% of the total dry weight of Nicotiana was found to be composed of alkaloids, where nicotine, nornicotine, anatabine, and anabasine are reported as the dominant alkaloids. Additionally, among the alkaloids present in Nicotiana, β-carboline (Harmane and Norharmane) and Kynurenines are found to show anti-tumor effects, especially in the cases of colon and breast cancers. Creating new or shunting of existing biosynthesis pathways in different species of Nicotiana resulted in de novo or increased synthesis of different anti-tumor molecules or their derivatives or precursors including Taxadiane (~22.5 µg/g), Artemisinin (~120 μg/g), Parthenolide (~2.05 ng/g), Costunolide (~60 ng/g), Etoposide (~1 mg/g), Crocin (~400 µg/g), Catharanthine (~60 ng/g), Tabersonine (~10 ng/g), Strictosidine (~0.23 mg/g), etc. Enriching the precursor pool, especially Dimethylallyl Diphosphate (DMAPP), down-regulating other bi-product pathways, compartmentalization or metabolic shunting, or organelle-specific reconstitution of the precursor pool, might trigger the enhanced accumulation of the targeted anti-cancer alkaloid in .
PubMed: 37233664
DOI: 10.3390/metabo13050623 -
Biomedicines Mar 2023Ulcerative colitis (UC) is an intractable disease that causes persistent colonic inflammation. Numerous studies have reported that smoking can afford clinical benefits...
Ulcerative colitis (UC) is an intractable disease that causes persistent colonic inflammation. Numerous studies have reported that smoking can afford clinical benefits in UC. This study aimed to elucidate whether nicotine, the main component in cigarettes, can exert pharmacological effects against experimental UC. To achieve this objective, we compared the effects of nicotine with those of structural nicotine analogs in a UC rodent model (Slc: Wistar rats, male, 9-week-old, and 220-250 g/rat). Nicotine, or a respective structural analog (nornicotine, cotinine, anabasine, myosmine, and anatabine), was administered intraperitoneally daily to rats ( = 6/group) exhibiting dextran sulfate sodium-induced experimental colitis. Examining the colon tissues of model rats, we compared disease severity, cytokine secretion, and α7 nicotine acetylcholine receptor (nAChR7) expression. We observed that nicotine administration induced weight loss at 2.35% in 10 days. Notably, the reduction in histological severity (score) of UC was more pronounced in rats treated with nicotine (score = 4.83, = 0.042) than in untreated rats (score = 8.17). Nicotine administration increased nAChR7 expression 6.88-fold ( = 0.022) in inflammatory sites of the colon, mainly by suppressing the production of interleukin (IL)-1β and IL-6. Moreover, the secretion of these cytokines was suppressed in lipopolysaccharide-stimulated rat macrophages (MΦ) treated with nicotine. In conclusion, nicotine better alleviates experimental UC than the examined structural analogs by activating nAChR7 expression and suppressing proinflammatory cytokines in MΦ.
PubMed: 36979901
DOI: 10.3390/biomedicines11030922 -
Toxins Jan 2023Nemerteans (also called Nemertines) are a phylum of predominantly marine worms that use toxins to capture prey and to defend themselves against predators....
Nemerteans (also called Nemertines) are a phylum of predominantly marine worms that use toxins to capture prey and to defend themselves against predators. Hoplonemerteans have a proboscis armed with one or more stylets used in prey capture and are taxonomically divided into Order Monostilifera, whose members possess a single large proboscis stylet, and Order Polystilifera, whose members have multiple small stylets. Many monostiliferans contain alkaloidal toxins, including anabaseine, that stimulate and then desensitize nicotinic acetylcholine receptors that are present in all animals. These compounds also interact with pyridyl chemoreceptors in crustaceans, reducing predation and larval settlement. Anabaseine has been a lead compound in the design of alpha7 nicotinic acetylcholine receptor agonists like GTS-21 (also called DMXBA) to treat disorders of cognition such as Alzheimer's disease and schizophrenia. These drug candidates also display anti-inflammatory activities of potential medical importance. Most polystiliferans live deep in open oceans and are relatively inaccessible. We fortunately obtained two live specimens of a large benthic polystiliferan, (), from the coast of Spain. MS and NMR analyses of the Ehrlich's reagent derivative allowed identification of anabaseine. A spectrophotometric assay for anabaseine, also based on its reaction with Ehrlich's reagent, revealed high concentrations of anabaseine in the body and proboscis. Apparently, the biosynthetic mechanism for producing anabaseine was acquired early in the evolution of the Hoplonemertea, before the monostiliferan-polystiliferan divergence.
Topics: Animals; Receptors, Nicotinic; Nicotinic Agonists; Anabasine; Toxins, Biological
PubMed: 36668866
DOI: 10.3390/toxins15010046 -
Molecules (Basel, Switzerland) Oct 2022A series of -acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested...
A series of -acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole fragments, while the adamantane derivatives showed the greatest antiviral effect. It was found that the majority of anabasine derivatives showed significant analgesic activity, reducing the pain response of animals to the irritating effect of acetic acid. The presence of a high level of antimicrobial and antiviral activity in newly synthesized compounds makes it possible to consider them promising for further study of their pharmacological properties.
Topics: Animals; Adamantane; Anabasine; Azoles; Pyridines; Analgesics; Anti-Bacterial Agents; Antiviral Agents; Structure-Activity Relationship; Microbial Sensitivity Tests
PubMed: 36364219
DOI: 10.3390/molecules27217387