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Journal of Medical Toxicology :... Mar 2011We present two cases of rare human poisoning in one family following ingestion of cooked leaves from the tobacco tree plant, Nicotiana glauca. The toxic principle of N.... (Review)
Review
We present two cases of rare human poisoning in one family following ingestion of cooked leaves from the tobacco tree plant, Nicotiana glauca. The toxic principle of N. glauca, anabasine (C10H14N2), is a small pyridine alkaloid, similar in both structure and effects to nicotine, but appears to be more potent in humans. A 73-year-old female tourist from France, without remarkable medical history, collapsed at home following a few hours long prodrome of dizziness, nausea, vomiting, and malaise. The symptoms developed shortly after eating N. glauca cooked leaves that were collected around her daughter's house in Jerusalem and mistaken for wild spinach. She was found unconscious, with dilated pupils and extreme bradycardia. Following resuscitation and respiratory support, circulation was restored. However, she did not regain consciousness and died 20 days after admission because of multi-organ failure. Anabasine was identified by gas chromatography/mass spectrometry method in N. glauca leaves and in the patient's urine. Simultaneously, her 18-year-old grandson developed weakness and myalgia after ingesting a smaller amount of the same meal. He presented to the same emergency room in a stable condition. His exam was remarkable only for sinus bradycardia. He was discharged without any specific treatment. He recovered in 24 h without any residual sequelae. These cases raise an awareness of the potential toxicity caused by ingestion of tobacco tree leaves and highlight the dangers of ingesting botanicals by lay public. Moreover, they add to the clinical spectrum of N. glauca intoxication.
Topics: Accidents, Home; Adolescent; Aged; Anabasine; Cooking; Fatal Outcome; Female; Humans; Israel; Male; Multiple Organ Failure; Plant Leaves; Poisoning; Nicotiana
PubMed: 20652661
DOI: 10.1007/s13181-010-0102-x -
International Journal For Parasitology.... Apr 2017Nematode parasites infect ∼2 billion people world-wide. Infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic acetylcholine...
Nematode parasites infect ∼2 billion people world-wide. Infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic acetylcholine receptors (nAChRs). There is an unmet need for novel therapeutic agents because of concerns about the development of resistance. We have selected Asu-ACR-16 from a significant nematode parasite genus, Ascaris suum, as a pharmaceutical target and nicotine as our basic moiety (EC 6.21 ± 0.56 μM, I 82.39 ± 2.52%) to facilitate the development of more effective anthelmintics. We expressed Asu-ACR-16 in Xenopus oocytes and used two-electrode voltage clamp electrophysiology to determine agonist concentration-current-response relationships and determine the potencies (ECs) of the agonists. Here, we describe the synthesis of a novel agonist, (S)-5-ethynyl-anabasine, and show that it is more potent (EC 0.14 ± 0.01 μM) than other nicotine alkaloids on Asu-ACR-16. Agonists acting on ACR-16 receptors have the potential to circumvent drug resistance to anthelmintics, like levamisole, that do not act on the ACR-16 receptors.
Topics: Anabasine; Animals; Ascaris suum; Drug Discovery; Levamisole; Nicotinic Agonists; Oocytes; Receptors, Nicotinic; Xenopus
PubMed: 28033523
DOI: 10.1016/j.ijpddr.2016.12.001 -
Ecology Oct 2019Bee populations have experienced declines in recent years, due in part to increased disease incidence. Multiple factors influence bee-pathogen interactions, including...
Bee populations have experienced declines in recent years, due in part to increased disease incidence. Multiple factors influence bee-pathogen interactions, including nectar and pollen quality and secondary metabolites. However, we lack an understanding of how plant interactions with their environment shape bee diet quality. We examined how plant interactions with the belowground environment alter floral rewards and, in turn, bee-pathogen interactions. Soil-dwelling mycorrhizal fungi are considered plant mutualists, although the outcome of the relationship depends on environmental conditions such as nutrients. In a 2 × 2 factorial design, we asked whether mycorrhizal fungi and nutrients affect concentrations of nectar and pollen alkaloids (anabasine and nicotine) previously shown to reduce infection by the gut pathogen Crithidia in the native bumble bee Bombus impatiens. To ask how plant interactions affect this common bee pathogen, we fed pollen and nectar from our treatment plants, and from a wildflower pollen control with artificial nectar, to bees infected with Crithidia. Mycorrhizal fungi and fertilizer both influenced flowering phenology and floral chemistry. While we found no anabasine or nicotine in nectar, high fertilizer increased anabasine and nicotine in pollen. Arbuscular mycorrhizal fungi (AMF) decreased nicotine concentrations, but the reduction due to AMF was stronger in high than low-nutrient conditions. AMF and nutrients also had interactive effects on bee pathogens via changes in nectar and pollen. High fertilizer reduced Crithidia cell counts relative to low fertilizer in AMF plants, but increased Crithidia in non-AMF plants. These results did not correspond with effects of fertilizer and AMF on pollen alkaloid concentrations, suggesting that other components of pollen or nectar were affected by treatments and shaped pathogen counts. Our results indicate that soil biotic and abiotic environment can alter bee-pathogen interactions via changes in floral rewards, and underscore the importance of integrative studies to predict disease dynamics and ecological outcomes.
Topics: Animals; Bees; Crithidia; Mycorrhizae; Nutrients; Parasites; Soil
PubMed: 31234229
DOI: 10.1002/ecy.2801 -
BMJ Open Jun 2021Continued smoking following a cancer diagnosis has substantial health risks including increased overall and cancer-specific mortality, risk of secondary malignancies,...
INTRODUCTION
Continued smoking following a cancer diagnosis has substantial health risks including increased overall and cancer-specific mortality, risk of secondary malignancies, cancer treatment toxicity and risk of surgical complications. These risks can be mitigated by quitting smoking. The preoperative period represents a prime opportunity in which to administer robust smoking cessation treatment to both improve health and support and improve surgical outcomes. We will conduct a randomised clinical trial to evaluate the effectiveness of financial incentives delivered contingent on biochemically verified smoking abstinence (contingency management (CM)) in patients with cancer undergoing surgery.
METHODS AND ANALYSIS
The study will take place across two study sites, and participants (N=282) who smoke, are diagnosed with or suspected to have any type of operable cancer and have a surgical procedure scheduled in the next 10 days to 5 weeks will be randomised to receive standard care plus Monitoring Only or CM prior to surgery. All patients will receive breath carbon monoxide (CO) tests three times per week, nicotine replacement therapy and counselling. The CM group will also earn payments for self-reported smoking abstinence confirmed by CO breath test ≤4 ppm on an escalating schedule of reinforcement (with a reset if they smoked). Point prevalence abstinence (PPA) outcomes (self-report of 7-day abstinence confirmed by CO≤4 ppm and/or anabasine ≤2 ng/mL) will be assessed on the day of surgery and 6 months after surgery. The effect of CM on 7-day PPA at the time of surgery and 6-month follow-up will be modelled using generalised linear mixed effects models.
ETHICS AND DISSEMINATION
This study has been reviewed and approved by the Medical University of South Carolina Institutional Review Board. We will disseminate our scientific results through traditional research-oriented outlets such as presentations at scientific meetings and publications in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT04605458.
Topics: Humans; Motivation; Neoplasms; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 34187835
DOI: 10.1136/bmjopen-2021-051226 -
Trials Aug 2021Financial incentives are an effective way of helping women to stop smoking during pregnancy. Unfortunately, most women who stop smoking at this time return to smoking...
BACKGROUND
Financial incentives are an effective way of helping women to stop smoking during pregnancy. Unfortunately, most women who stop smoking at this time return to smoking within 12 months of the infant's birth. There is no evidence for interventions that are effective at preventing postpartum smoking relapse. Financial incentives provided after the birth may help women to sustain cessation. This randomised controlled trial will assess the effectiveness and cost-effectiveness of financial incentives to help women who are abstinent from smoking at end-of-pregnancy to avoid return to smoking up to 12 months postpartum.
METHODS
This is a UK-based, multi-centre, three-arm, superiority, parallel group, individually randomised controlled trial, with 1:1:1 allocation. It will compare the effectiveness of two financial incentive interventions with each other (one intervention for up to 3 months postpartum offering up to £120 of incentives (£60 for the participant and £60 for a significant other support); the other for up to 12 months postpartum with up to £300 of incentives (£240 for the participant and £60 for a significant other support) and with a no incentives/usual care control group. Eligible women will be between 34 weeks gestation and 2 weeks postpartum, abstinent from smoking for at least 4 weeks, have an expired carbon monoxide (CO) reading < 4 parts per million (ppm), aged at least 16 years, intend remaining abstinent from smoking after the birth and able to speak and read English. The primary outcome is self-reported, lapse-free, smoking abstinence from the last quit attempt in pregnancy until 12 months postpartum, biochemically validated by expired CO and/or salivary cotinine or anabasine. Outcomes will be analysed by intention-to-treat and regression models used to compare the proportion of abstinent women between the two intervention groups and between each intervention group and the control group. An economic evaluation will assess the cost-effectiveness of offering incentives and a qualitative process evaluation will examine barriers and facilitators to trial retention, effectiveness and implementation.
DISCUSSION
This pragmatic randomised controlled trial will test whether offering financial incentives is effective and cost-effective for helping women to avoid smoking relapse during the 12 months after the birth of their baby.
TRIAL REGISTRATION
International Standard Randomised Controlled Trial Number 55218215 . Registered retrospectively on 5th June 2019.
Topics: Female; Humans; Infant; Motivation; Multicenter Studies as Topic; Postpartum Period; Pregnancy; Randomized Controlled Trials as Topic; Retrospective Studies; Smoking; Smoking Cessation
PubMed: 34340694
DOI: 10.1186/s13063-021-05480-6 -
Scientific Reports Nov 2016Nectar and pollen contain diverse phytochemicals that can reduce disease in pollinators. However, prior studies showed variable effects of nectar chemicals on infection,...
Nectar and pollen contain diverse phytochemicals that can reduce disease in pollinators. However, prior studies showed variable effects of nectar chemicals on infection, which could reflect variable phytochemical resistance among parasite strains. Inter-strain variation in resistance could influence evolutionary interactions between plants, pollinators, and pollinator disease, but testing direct effects of phytochemicals on parasites requires elimination of variation between bees. Using cell cultures of the bumble bee parasite Crithidia bombi, we determined (1) growth-inhibiting effects of nine floral phytochemicals and (2) variation in phytochemical resistance among four parasite strains. C. bombi growth was unaffected by naturally occurring concentrations of the known antitrypanosomal phenolics gallic acid, caffeic acid, and chlorogenic acid. However, C. bombi growth was inhibited by anabasine, eugenol, and thymol. Strains varied >3-fold in phytochemical resistance, suggesting that selection for phytochemical resistance could drive parasite evolution. Inhibitory concentrations of thymol (4.53-22.2 ppm) were similar to concentrations in Thymus vulgaris nectar (mean 5.2 ppm). Exposure of C. bombi to naturally occurring levels of phytochemicals-either within bees or during parasite transmission via flowers-could influence infection in nature. Flowers that produce antiparasitic phytochemicals, including thymol, could potentially reduce infection in Bombus populations, thereby counteracting a possible contributor to pollinator decline.
Topics: Anabasine; Animals; Bees; Cells, Cultured; Crithidia; Eugenol; Host-Parasite Interactions; Phytochemicals; Thymol; Thymus Plant
PubMed: 27883009
DOI: 10.1038/srep37087 -
BMC Ecology Nov 2020Invasive plant species pose a significant threat for fragile isolated ecosystems, occupying space, and consuming scarce local resources. Recently though, an additional...
BACKGROUND
Invasive plant species pose a significant threat for fragile isolated ecosystems, occupying space, and consuming scarce local resources. Recently though, an additional adverse effect was recognized in the form of its secondary metabolites entering the food chain. The present study is elaborating on this subject with a specific focus on the Nicotiana glauca Graham (Solanaceae) alkaloids and their occurrence and food chain penetrability in Mediterranean ecosystems. For this purpose, a targeted liquid chromatography electrospray tandem mass spectrometric (LC-ESI-MS/MS) analytical method, encompassing six alkaloids and one coumarin derivative, utilizing hydrophilic interaction chromatography (HILIC) was developed and validated.
RESULTS
The method exhibited satisfactory recoveries, for all analytes, ranging from 75 to 93%, and acceptable repeatability and reproducibility. Four compounds (anabasine, anatabine, nornicotine, and scopoletin) were identified and quantified in 3 N. glauca flowers extracts, establishing them as potential sources of alien bio-molecules. The most abundant constituent was anabasine, determined at 3900 μg/g in the methanolic extract. These extracts were utilized as feeding treatments on Apis mellifera honeybees, resulting in mild toxicity documented by 16-18% mortality. A slightly increased effect was elicited by the methanolic extract containing anabasine at 20 μg/mL, where mortality approached 25%. Dead bees were screened for residues of the N. glauca flower extracts compounds and a significant mean concentration of anabasine was evidenced in both 10 and 20 μg/mL treatments, ranging from 51 to 92 ng/g per bee body weight. Scopoletin was also detected in trace amounts.
CONCLUSIONS
The mild toxicity of the extracts in conjunction with the alkaloid and coumarin residual detection in bees, suggest that these alien bio-molecules are transferred within the food chain, suggesting a chemical invasion phenomenon, never reported before.
Topics: Alkaloids; Animals; Bees; Ecosystem; Reproducibility of Results; Tandem Mass Spectrometry; Nicotiana
PubMed: 33158433
DOI: 10.1186/s12898-020-00325-3 -
Drug and Alcohol Dependence Aug 2015While nicotine is the primary addictive compound in tobacco, other tobacco constituents including minor alkaloids (e.g., nornicotine, anabasine) may also contribute to...
BACKGROUND
While nicotine is the primary addictive compound in tobacco, other tobacco constituents including minor alkaloids (e.g., nornicotine, anabasine) may also contribute to tobacco addiction by mimicking or enhancing the effects of nicotine. Further evaluating the behavioral effects of minor alkaloids is essential for understanding their impact on tobacco addiction and informing development of tobacco product standards by the FDA.
METHODS
This study compared the addiction-related effects of nicotine and the minor alkaloids nornicotine, anabasine, myosmine, anatabine, and cotinine on intracranial self-stimulation (ICSS) thresholds in rats.
RESULTS
Acute injection of nicotine produced reinforcement-enhancing (ICSS threshold-decreasing) effects at low to moderate doses, and reinforcement-attenuating/aversive (ICSS threshold-increasing) effects at high doses. Nornicotine and anabasine produced similar biphasic effects on ICSS thresholds, although with lower potency compared to nicotine. Myosmine only elevated ICSS thresholds at relatively high doses, while anatabine and cotinine did not influence ICSS thresholds at any dose. None of the alkaloids significantly influenced ICSS response latencies, indicating a lack of nonspecific motoric effects.
CONCLUSIONS
These findings indicate that some minor tobacco alkaloids can either fully (nornicotine, anabasine) or partially (myosmine) mimic nicotine's addiction-related effects on ICSS, albeit at reduced potency. These findings emphasize the need for further study of the abuse potential of minor alkaloids, including evaluation of their effects when combined with nicotine and other tobacco constituents to better simulate tobacco exposure in humans. Such work is essential for informing FDA regulation of tobacco products and could also lead to the development of novel pharmacotherapies for tobacco addiction.
Topics: Alkaloids; Anabasine; Animals; Brain; Cotinine; Male; Nicotine; Pyridines; Rats; Self Stimulation
PubMed: 26094184
DOI: 10.1016/j.drugalcdep.2015.06.005 -
Journal of Chromatography. B,... Nov 2011A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of nicotine (NIC), cotinine (COT), nornicotine (NNIC), norcotinine...
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of nicotine (NIC), cotinine (COT), nornicotine (NNIC), norcotinine (NCOT), nicotine-N-β-D-glucuronide (NIC GLUC), cotinine-N-β-D-glucuronide (COT GLUC), nicotine-1'-oxide (NNO), cotinine-N-oxide (CNO), trans-3'-hydroxycotinine (3-HC), anabasine (AB) and anatabine (AT) was modified and validated for quantification of these selected analytes in rat brain tissue. This analytical method provides support for preclinical NIC pharmacokinetic and toxicological studies after controlled dosing protocols. After brain homogenization and solid-phase extraction, target analytes and corresponding deuterated internal standards were chromatographically separated on a Discovery(®) HS F5 HPLC column with gradient elution and analyzed by LC-MS/MS in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. Method linearity was assessed and calibration curves were determined over the following ranges: 0.1-7.5 ng/mg for NIC, COT GLUC and AB; and 0.025-7.5 ng/mg for COT, NNIC, NCOT, NIC GLUC, NNO, CNO, 3-HC and AT (R(2)≥0.99 for all analytes). Extraction recoveries ranged from 64% to 115%, LC-MS/MS matrix effects were ≤21%, and overall process efficiency ranged from 57% to 93% at low and high quality control concentrations. Intra- and inter-assay imprecisions and accuracy for all analytes were ≤12.9% and ≥86%, respectively. The method was successfully applied to quantification of NIC and metabolites in the brain of post-natal day 90 rats that were sacrificed 2-h after a single 0.8 mg/kg s.c. administration of (-)NIC. In these tissues, striatal concentrations were 204.8±49.4, 138.2±14.2 and 36.1±6.1 pg/mg of NIC, COT and NNIC, respectively. Concentrations of NIC, COT and NNIC in the remaining whole brain (RWhB) were 183.3±68.0, 130.0±14.1 and 46.7±10.3 pg/mg, respectively. Quantification of these same analytes in plasma was also performed by a previously validated method. NIC, COT, NNIC, NCOT, NNO and CNO were detected in plasma with concentrations comparable to those reported in previous studies. However, and in contrast to brain tissues, COT concentrations in plasma were significantly higher than were those of NIC (194.6±18.6 ng/mL versus 52.7±12.9 ng/mL). Taken together, these results demonstrate that a sensitive and selective method has been developed for the determination of NIC biomarkers in rat brain.
Topics: Alkaloids; Anabasine; Animals; Biomarkers; Brain Chemistry; Chromatography, Liquid; Cotinine; Linear Models; Male; Nicotine; Pyridines; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry
PubMed: 21963483
DOI: 10.1016/j.jchromb.2011.09.026 -
The AAPS Journal Oct 2005The minor tobacco alkaloids nornicotine, anabasine, and anatabine from Nicotiana tobacum are known to possess nicotinic receptor agonist activity, although they are...
The minor tobacco alkaloids nornicotine, anabasine, and anatabine from Nicotiana tobacum are known to possess nicotinic receptor agonist activity, although they are relatively less potent than S-(-)-nicotine, the principal tobacco alkaloid. Previous pharmacological investigations and structure-activity studies have been limited owing to the lack of availability of the optically pure forms of these minor alkaloids. We now report a 2-step synthetic procedure for the enantioselective synthesis of the optical isomers of nornicotine and anabasine, and a modified procedure for the synthesis of anatabine enantiomers. These procedures involve initial formation of the chiral ketimine resulting from the condensation of either 1R, 2R, 5R-(+)- or 1S, 2S, 5S-(-)-2-hydroxy-3-pinanone with 3-(aminomethyl)pyridine followed by enantioselective C-alkylation with an appropriate halogenoalkane or halogenoalkene species, N-deprotection, and base-catalyzed intramolecular ring closure, to form the appropriate, chirally pure minor tobacco alkaloid. Using this approach, the R-(+)- and S-(-)-enantiomers of the above minor tobacco alkaloids were obtained in good overall chemical yield and excellent enantomeric excess.
Topics: Alkaloids; Anabasine; Nicotine; Pyridines; Stereoisomerism; Nicotiana
PubMed: 16353951
DOI: 10.1208/aapsj070375