Tobacco Alkaloids Research Articles

Protonating and determining myosmine intactly by association with citrate anion

Myosmine can not be separated from nornicotine, nicotine and anabasine intactly by capillary zone electrophoresis (CZE) with a phosphate buffer. Using citrate solution at pH 6.5 as a CZE buffer, myosmine is protonated intactly by H(+), charged positively and then separated from other tobacco alkaloids on the baseline. Its sensitivity is ten times higher than gas chromatography (GC) with a nitrogen-phosphorus detector (NPD). The mechanism for protonating myosmine intactly is discussed and the utility of the new method is testified, too.

Application of catalytic dynamic resolution of N-Boc-2-lithiopiperidine to the asymmetric synthesis of 2-aryl and 2-vinyl piperidines.

The highly enantioselective synthesis of 2-aryl- and 2-vinyl-piperidines has been accomplished through a catalytic dynamic resolution (CDR) of N-Boc-2-lithiopiperidine. The method has been applied to the synthesis of both enantiomers of the tobacco alkaloid anabasine.

Effects of Nicotine Administration and Nicotine Cessation on Bone Histomorphometry and Bone Biomarkers in Sprague–Dawley Male Rats

Nicotine is a major alkaloid of tobacco, which can increase free radical formation, leading to osteoporosis. The effects of nicotine administration and cessation on bone histomorphometry and biomarkers were studied in 28 Sprague-Dawley male rats. Rats aged 3months and weighing 250-300g were divided into four groups: control (C, normal saline for 4months), nicotine for 2months (N2), nicotine for 4months (N4), and nicotine cessation (NC). The NC group was given nicotine for the first 2months and then allowed to recover for the following 2months without nicotine. Histomorphometric analysis was done using an image analyzer. ELISA kits were used to measure serum osteocalcin (bone formation marker) and pyridinoline (PYD, bone resorption marker) levels at month 0, month 2, and month 4. All test groups showed a significant decrease in BV/TV, Ob.S/BS, dLS/BS, MAR, BFR/BS, and osteocalcin levels and an increase in sLS/BS and PYD levels compared to group C. No significant differences were observed in all parameters measured among the test groups, except for MAR and BFR/BS. In conclusion, nicotine administration at a dose of 7mg/kg for 2 and 4months has detrimental effects on bone metabolism. Nicotine administration at 7mg/kg for 2months is sufficient to produce significant effects on bone histomorphometric parameters and biomarkers. In addition, prolonging the treatment for another 2months did not show any significant differences. Cessation of nicotine for 2months did not reverse the effects.

High-Throughput Simultaneous Analysis of Five Urinary Metabolites of Areca Nut and Tobacco Alkaloids by Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry with On-Line Solid-Phase Extraction

Areca nut and tobacco are commonly used drugs worldwide and have been frequently used in combination. We describe the use of on-line solid-phase extraction and isotope-dilution liquid chromatography-tandem mass spectrometry for the simultaneous measurement of five major urinary metabolites of both areca nut and tobacco alkaloids, namely, arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine. Automated purification of urine was accomplished with a column-switching device. After the addition of deuterium-labeled internal standards, urine samples were directly analyzed within 13 minutes. This method was applied to measure urinary metabolites in 90 healthy subjects to assess areca nut/tobacco exposure. Urinary time course of arecoline, arecaidine, and N-methylnipecotic acid was investigated in five healthy nonchewers after oral administration of areca nut water extracts. The limits of detection were 0.016 to 0.553 ng/mL. Interday and intraday imprecision were <10%. Mean recoveries of five metabolites in urine were 97% to 114%. Mean urinary concentrations of arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine in regular areca nut chewers also smokers were 23.9, 5,816, 1,298, 2,635, and 1,406 ng/mg creatinine, respectively. Time course study revealed that after administration of areca nuts extracts, the major urinary metabolite was arecaidine with a half-life of 4.3 hours, followed by N-methylnipecotic acid with a half-life of 7.9 hours, and very low levels of arecoline with a half-life of 0.97 hour. This on-line solid-phase extraction liquid chromatography-tandem mass spectrometry method firstly provides high-throughput direct analysis of five urinary metabolites of areca nut/tobacco alkaloids. This method may facilitate the research into the oncogenic effects of areca nut/tobacco exposure.

From smoking to lung cancer: the CHRNA5/A3/B4 connection.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that modulate key physiological processes ranging from neurotransmission to cancer signaling. These receptors are activated by the neurotransmitter, acetylcholine, and the tobacco alkaloid, nicotine. Recently, the gene cluster encoding the alpha3, alpha5 and beta4 nAChR subunits received heightened interest after a succession of linkage analyses and association studies identified multiple single-nucleotide polymorphisms in these genes that are associated with an increased risk for nicotine dependence and lung cancer. It is not clear whether the risk for lung cancer is direct or an effect of nicotine dependence, as evidence for both scenarios exist. In this study, we summarize the body of work implicating nAChRs in the pathogenesis of lung cancer, with special focus on the clustered nAChR subunits and their emerging role in this disease state.

A sensitive enzyme immunoassay for measuring cotinine in passive smokers

Background Both active smoking and passive exposure to tobacco smoke are major risk factors for cardiovascular, pulmonary, and oncological diseases. The serum level of cotinine, a major proximate metabolite of nicotine, reflects active or passive exposure to tobacco smoke. However, currently available enzyme-linked immunosorbent assays (ELISAs) for cotinine have limited sensitivity, and a high-throughput quantification of the severity of passive exposure to tobacco smoke has not been possible thus far. Methods We generated a phage display of combinatorial antibody library, from which we selected a recombinant antibody against cotinine, developed a sensitive ELISA using this antibody, and evaluated the method in a clinical setting and an animal model. Results The limits of detection and the lower limit of quantification were 31 pg/mL and 1 ng/mL cotinine, respectively. The intra- and inter-assay precisions based on three quality control samples were 3.8–13.5% and 14.0–15.0%, respectively. No significant interference from nicotine, trans-3'-hydroxy cotinine, tobacco alkaloids, or other serum components was found. When we applied our ELISA to serum samples from 36 volunteers, the serum cotinine levels were clustered into two groups, which exactly corresponded to their smoking behavior and this ELISA yielded reproducible and accurate results, which were comparable to those of LC/MS in a split assay. In animal studies, we were able to distinguish between rats injected with a nicotine dose equivalent to that of passive exposure to tobacco and rats without exposure. Conclusion The competitive ELISA described here is useful for the detection and quantification of the severity of risk of passive smoking.

The effects of dopaminergic drugs in the ventral hippocampus of rats in the nicotine-induced anxiogenic-like response

Nicotine an active alkaloid of tobacco has dopaminergic properties. The drug alters anxiety-like behavior in rodents. Ventral hippocampus (VHC) may be a site for modulation of anxiety-like behaviors. The possible involvement of ventral hippocampal dopaminergic receptor mechanism in the nicotine influence on anxiogenic-like response has been investigated in the present study. The effects of apomorphine, sulpiride and SCH23390 on nicotine response in elevated plus maze in rats have been investigated. Intraperitoneal administration of nicotine (0.6 mg/kg) decreased percentage of open arm time (%OAT) but not percentage of open arm entries (%OAE) and locomotor activity, indicating an anxiogenic-like response. Intra-hippocampal injection (intra-VHC) of apomorphine, a D 1/D 2 dopamine receptor agonist (0.1 and 0.2 μg/rat) also caused anxiogenic-like effects, but the drug blocked that of nicotine. Intra-VHC administration of the D 2 receptor antagonist, sulpiride (1, 2.5 and 5 μg/rat) or the D 1 receptor antagonist, SCH23390 (0.01, 0.1 and 1 μg/rat) did not elicit any response. However, pretreatment with sulpiride (1 μg/rat) or SCH23390 (0.1 μg/rat) decreased nicotine's effect. The results may indicate a modulatory effect for the D 1 and D 2 dopamine receptors of VHC in the anxiogenic-like response induced by nicotine.

Investigation of enhancement effects of nicotine on cholinergic neurotransmission in isolated rabbit gastric fundus: role of antioxidants

Nicotine, which is tobacco alkaloid, still induces interests for researchers because of smokers addiction to nicotine. Nicotine having influence on the neuronal acetylcholine receptors (nAChRs) increases release of most certain neurotransmitters from the nerve endings. Also, nicotine, affecting the mitochondrial respiratory chains, contributes to the formation of reactive oxygen species. In the present study, we investigated the effects of nicotine on smooth muscles of gastric fundus on the electrical field stimulation (EFS) that induces transition contraction via stimulation nAChRs. In addition, we aimed to investigate the interaction between release of acetylcholine, induced by nicotine, and the effects of reactive oxygen species. Therefore, the effects of allopurinol (10(-6)-10(-5) M), deferoxamine (10(-4) M) and mannitol (10(-4)-5 x 10(-3) M) were tested on the transient contraction induced by nicotine. In conclusion, mannitol (5 x 10(-3) M) significantly reduced contractile response to nicotine on EFS only in high concentration. Whereas in small concentrations mannitol (10(-4) M) statistically did not cause any results. Deferoxamine and allopurinol also did not have any significant response.

A novel validated procedure for the determination of nicotine, eight nicotine metabolites and two minor tobacco alkaloids in human plasma or urine by solid-phase extraction coupled with liquid chromatography–electrospray ionization–tandem mass spectrometry

A novel validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) procedure was developed and fully validated for the simultaneous determination of nicotine-N-β- d-glucuronide, cotinine-N-oxide, trans-3-hydroxycotinine, norcotinine, trans-nicotine-1′-oxide, cotinine, nornicotine, nicotine, anatabine, anabasine and cotinine-N-β- d-glucuronide in human plasma or urine. Target analytes and corresponding deuterated internal standards were extracted by solid-phase extraction and analyzed by LC–MS/MS with electrospray ionization (ESI) using multiple reaction monitoring (MRM) data acquisition. Calibration curves were linear over the selected concentration ranges for each analyte, with calculated coefficients of determination ( R 2) of greater than 0.99. The total extraction recovery (%) was concentration dependent and ranged between 52–88% in plasma and 51–118% in urine. The limits of quantification for all analytes in plasma and urine were 1.0 ng/mL and 2.5 ng/mL, respectively, with the exception of cotinine-N-β- d-glucuronide, which was 50 ng/mL. Intra-day and inter-day imprecision were ≤14% and ≤17%, respectively. Matrix effect (%) was sufficiently minimized to ≤19% for both matrices using the described sample preparation and extraction methods. The target analytes were stable in both matrices for at least 3 freeze–thaw cycles, 24 h at room temperature, 24 h in the refrigerator (4 °C) and 1 week in the freezer (−20 °C). Reconstituted plasma and urine extracts were stable for at least 72 h storage in the liquid chromatography autosampler at 4 °C. The plasma procedure has been successfully applied in the quantitative determination of selected analytes in samples collected from nicotine-abstinent human participants as part of a pharmacokinetic study investigating biomarkers of nicotine use in plasma following controlled low dose (7 mg) transdermal nicotine delivery. Nicotine, cotinine, trans-3-hydroxycotinine and trans-nicotine-1′-oxide were detected in the particular sample presented herein. The urine procedure has been used to facilitate the monitoring of unauthorized tobacco use by clinical study participants at the time of physical examination (before enrollment) and on the pharmacokinetic study day.

A Straightforward Synthesis of (S)-Anabasine via the Catalytic, Enantio­selective Vinylogous Mukaiyama-Mannich Reaction

The tobacco alkaloid (S)-anabasine was synthesized by a straightforward 4-step sequence with the catalytic enantioselective vinylogous Mannich reaction as a key step. Only 3 mol% of a structurally optimized chiral BINOL-based phosphoric acid was employed to control the absolute configuration of the natural product.

Analysis of myosmine, cotinine and nicotine in human toenail, plasma and saliva

Myosmine is a minor tobacco alkaloid with widespread occurrence in the human diet. Myosmine is genotoxic in human cells and is readily nitrosated and peroxidated yielding reactive intermediates with carcinogenic potential. For biomonitoring of short-term and long-term exposure, analytical methods were established for determination of myosmine together with nicotine and cotinine in plasma, saliva and toenail by gas chromatography–mass spectrometry (GC/MS). Validation of the method with samples of 14 smokers and 10 non-smokers showed smoking-dependent differences of myosmine in toenails (66 ± 56 vs 21 ± 15 ng g−1, p <0.01) as well as saliva (2.54 ± 2.68 vs 0.73 ± 0.65 ng ml−1, p <0.01). However, these differences were much smaller than those with nicotine (1971 ± 818 vs 132 ± 82 ng g−1, p <0.0001) and cotinine (1237 ± 818 vs <35 ng g−1) in toenail and those of cotinine (97.43 ± 84.54 vs 1.85 ± 4.50 ng ml−1, p <0.0001) in saliva. These results were confirmed in plasma samples from 84 patients undergoing gastro-oesophageal endoscopy. Differences between 25 smokers and 59 non-smokers are again much lower for myosmine (0.30 ± 0.35 vs 0.16 ± 0.18 ng ml−1, p <0.05) than for cotinine (54.67 ± 29.63 vs 0.61 ± 1.82 ng ml−1, p <0.0001). In conclusion, sources other than tobacco contribute considerably to the human body burden of myosmine.

The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats

Several minor tobacco alkaloids have been found to exhibit properties pharmacologically relevant to the addictive profile of tobacco; however, little is known of their effects on a behavioural model of drug addiction. In this study we compared the locomotor and reinforcing effects of intravenous nicotine (30 microg/kg per infusion) vs. a cocktail of nicotine plus five minor alkaloids found in tobacco smoke (anabasine, nornicotine, anatabine, cotinine and myosmine). Rats were initially tested for their locomotor response to nicotine or nicotine plus the minor alkaloids with six intravenous injections over 1 h. We then assessed the spontaneous acquisition of intravenous self-administration with nicotine or nicotine plus the minor alkaloids, under a fixed-ratio 1 schedule followed by responding on a fixed-ratio 5 schedule, progressive-ratio schedule and a single within-session ascending dose-response test. The activity test was repeated following the progressive-ratio phase to assess locomotor sensitization. A second group of rats were then tested on the locomotor procedure to better clarify the role of each individual minor alkaloid in nicotine-induced locomotor activity. Compared to nicotine alone, addition of the minor tobacco alkaloids increased locomotor activity and increased locomotor sensitization following self-administration. During fixed-ratio 5, progressive ratio and the dose-response test, rats receiving nicotine plus the minor alkaloids responded significantly more than those receiving nicotine alone. Testing of each minor alkaloid in the second experiment indicated that anatabine, cotinine and myosmine individually increased nicotine-induced locomotor activity. These results suggest that the minor tobacco alkaloids, particularly anatabine, cotinine and myosmine, may increase the motivation for nicotine and thus facilitate smoking behaviour.

Inhibition of Human Aromatase by Myosmine

Myosmine, a minor tobacco alkaloid widely occurring in food products of plant and animal origin, inhibits the conversion of testosterone to estradiol by human aromatase (IC(50): 33+/-2 microM) sevenfold more potent than nicotine (IC(50): 223+/-10 microM) and may have implications for sexual hormone homoeostasis.

Vacuolar transport of nicotine is mediated by a multidrug and toxic compound extrusion (MATE) transporter in Nicotiana tabacum

Alkaloids play a key role in plant defense mechanisms against pathogens and herbivores, but the plants themselves need to cope with their toxicity as well. The major alkaloid of the Nicotiana species, nicotine, is translocated via xylem transport from the root tissues where it is biosynthesized to the accumulation sites, the vacuoles of leaves. To unravel the molecular mechanisms behind this membrane transport, we characterized one transporter, the tobacco ( Nicotiana tabacum ) jasmonate-inducible alkaloid transporter 1 (Nt-JAT1), whose expression was coregulated with that of nicotine biosynthetic genes in methyl jasmonate-treated tobacco cells. Nt-JAT1, belonging to the family of multidrug and toxic compound extrusion transporters, was expressed in roots, stems, and leaves, and localized in the tonoplast of leaf cells. When produced in yeast cells, Nt-JAT1 occurred mainly in the plasma membrane and showed nicotine efflux activity. Biochemical analysis with proteoliposomes reconstituted with purified Nt-JAT1 and bacterial F 0 F 1 -ATPase revealed that Nt-JAT1 functioned as a proton antiporter and recognized endogenous tobacco alkaloids, such as nicotine and anabasine, and other alkaloids, such as hyoscyamine and berberine, but not flavonoids. These findings strongly suggest that Nt-JAT1 plays an important role in the nicotine translocation by acting as a secondary transporter responsible for unloading of alkaloids in the aerial parts and deposition in the vacuoles.

Synthesis and Spectroscopic Comparison of the Eight Methyl-2,3’-bipyridyls and Identification of a Hoplonemertine Alkaloid as 3-Methyl-2,3’-bipyridyl

The pyridyl ring is frequently found in natural products and drugs. While bipyridyls have served as useful scaffolds for development of industrial and pesticidal chemicals, their biological properties are still not well understood. Only 2,3'-bipyridyl, of the six isomeric bipyridyls, has been reported as a natural product in tobacco plants and in a hoplonemertine marine worm, Amphiporus angulatus (Aa), which uses its pyridyl alkaloid-rich venom to paralyze its crustacean prey and chemically defend itself against predators. Here we report for the first time the synthesis and spectroscopic properties of all eight possible methyl 2,3'-bipyridyl isomers and use this data to identify a trace alkaloidal constituent of Aa as 3-methyl-2,3'-bipyridyl. This is only the second reported instance of a methyl-bipyridyl being found as a natural product, the first being the tobacco alkaloid 5-methyl-2,3'-bipyridyl.

Multidrug and toxic compound extrusion-type transporters implicated in vacuolar sequestration of nicotine in tobacco roots.

Nicotine is a major alkaloid accumulating in the vacuole of tobacco (Nicotiana tabacum), but the transporters involved in the vacuolar sequestration are not known. We here report that tobacco genes (NtMATE1 and NtMATE2) encoding transporters of the multidrug and toxic compound extrusion (MATE) family are coordinately regulated with structural genes for nicotine biosynthesis in the root, with respect to spatial expression patterns, regulation by NIC regulatory loci, and induction by methyl jasmonate. Subcellular fractionation, immunogold electron microscopy, and expression of a green fluorescent protein fusion protein all suggested that these transporters are localized to the vacuolar membrane. Reduced expression of the transporters rendered tobacco plants more sensitive to the application of nicotine. In contrast, overexpression of NtMATE1 in cultured tobacco cells induced strong acidification of the cytoplasm after jasmonate elicitation or after the addition of nicotine under nonelicited conditions. Expression of NtMATE1 in yeast (Saccharomyces cerevisiae) cells compromised the accumulation of exogenously supplied nicotine into the yeast cells. The results imply that these MATE-type proteins transport tobacco alkaloids from the cytosol into the vacuole in exchange for protons in alkaloid-synthesizing root cells.

Evaluation of the mutagenic effects of myosmine in human lymphocytes using the HPRT gene mutation assay

The minor tobacco alkaloid myosmine is implicated in DNA damage through pyridyloxobutylation similar to the tobacco-specific nitrosamines (TSNA). In contrast to TSNA, occurrence of myosmine is not restricted to tobacco. Myosmine is genotoxic to human cells in the comet assay. In this study, the mutagenic effect of myosmine was evaluated using the cloning hypoxanthine-guanine phosphoribosyltransferase ( HPRT) gene mutation assay. Four hour exposure of isolated peripheral blood lymphocytes from 14 subjects homozygous for the Leu84 wild-type of the O 6-methylguanine-DNA-methyltransferase ( MGMT) gene to 1 mM of myosmine increased mutant frequency from 0.73 ± 0.58 × 10 −6 in control to 1.14 ± 0.89 × 10 −6 lymphocytes ( P < 0.05). These new data further confirm the mutagenic effects of myosmine.

A PIP-family protein is required for biosynthesis of tobacco alkaloids

Plants in the Nicotiana genus produce nicotine and related pyridine alkaloids as a part of their chemical defense against insect herbivores. These alkaloids are formed by condensation of a derivative of nicotinic acid, but the enzyme(s) involved in the final condensation step remains elusive. In Nicotiana tabacum, an orphan reductase A622 and its close homolog A622L are coordinately expressed in the root, upregulated by methyl jasmonate treatment, and controlled by the NIC regulatory loci specific to the biosynthesis of tobacco alkaloids. Conditional suppression of A622 and A622L by RNA interference inhibited cell growth, severely decreased the formation of all tobacco alkaloids, and concomitantly induced an accumulation of nicotinic acid beta-N-glucoside, a probable detoxification metabolite of nicotinic acid, in both hairy roots and methyl jasmonate-elicited cultured cells of tobacco. N-methylpyrrolinium cation, a precursor of the pyrrolidine moiety of nicotine, also accumulated in the A622(L)-knockdown hairy roots. We propose that the tobacco A622-like reductases of the PIP family are involved in either the formation of a nicotinic acid-derived precursor or the final condensation reaction of tobacco alkaloids.

Urinary Tobacco Alkaloid Measurement in Patients Having Thromboangiitis Obliterans

To the Editor: The recent Residents' Clinic by Geske et al1Geske JB Calvin AD McDonald FS 37-year-old man with painful foot.Mayo Clin Proc. 2008; 83: 821-824Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar points out the difficulties of diagnosing thromboangiitis obliterans (TAO or Buerger disease) when the patient admits past smoking but denies current tobacco use.1Geske JB Calvin AD McDonald FS 37-year-old man with painful foot.Mayo Clin Proc. 2008; 83: 821-824Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Denial and rationalization are common features of tobacco dependence, and an objective measure of tobacco use is critical in such circumstances. The tobacco alkaloids nicotine and cotinine can bemeasured in blood and urine and are biomarkers of nicotine exposure. Serum cotinine, with an elimination half-life of 18 to 20 hours, is able to detect nicotine use after 2 to 3 days of abstinence. However, elevated levels of both nicotine and cotinine are also common after use of therapeutic nicotine replacement products and so are not specific markers of tobacco use. In contrast, the urinary tobacco alkaloids anabasine and nornicotine are specific for tobacco use and can be used to distinguish patients who are abstaining from tobacco and using nicotine replacement therapy from those who are smoking.2Moyer TP Charlson JR Enger RJ et al.Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles.Clin Chem. 2002; 48: 1460-1471PubMed Google Scholar Because anabasine and nornicotine are not metabolites of nicotine, they indicate current tobacco use if detected in urine. As mentioned by Geske et al,1Geske JB Calvin AD McDonald FS 37-year-old man with painful foot.Mayo Clin Proc. 2008; 83: 821-824Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar the relationship of tobacco to TAO has been known for decades. In an early series from Mayo Clinic, only 5 of 350 men (aged 25-55 years) with TAO were nonsmokers.3Barker N The tobacco factor in thromboangiitis obliterans.Proc Staff Meet Mayo Clin. 1931; 6: 65-68Google Scholar In the discussion, Dr W. J. Mayo quipped: “On the whole, smoking seems a habit which has possibilities for harm, and has little to its credit.” Of course, this report from Mayo Clinic dates to 1931, long before most of the detrimental effects of tobacco use were known. However, as Geske et al1Geske JB Calvin AD McDonald FS 37-year-old man with painful foot.Mayo Clin Proc. 2008; 83: 821-824Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar point out, the misconception that tobacco dependence treatment is unsuccessful in patients with TAO is common. Quite the contrary, we found that smokers with TAO were no more tobacco dependent than smokers with coronary artery disease; thus, treatment should be aggressively pursued in these patients.4Cooper LT Henderson SS Ballman KV et al.A prospective, case-control study of tobacco dependence in thromboangiitis obliterans (Buerger's disease).Angiology. 2006; 57: 73-78Crossref PubMed Scopus (19) Google Scholar We also observed that patients with TAO smoked fewer cigarettes per day than patients with coronary artery disease and were more likely to have made a serious attempt to stop in the past. Certainly for smokers with such a severe medical problem as TAO, residential treatment for tobacco dependence offers the best option to stop and remain abstinent from smoking.5Hooten WM Bruns HK Hays JT Inpatient treatment of severe nicotine dependence in a patient with thromboangiitis obliterans (Buerger's disease).Mayo Clin Proc. 1998; 73: 529-532Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar An overall 1-year smoking abstinence rate of 45% was reported after an 8-day residential treatment program.6Hays JT Wolter TD Eberman KM Croghan IT Offord KP Hurt RD Residential (inpatient) treatment compared with outpatient treatment for nicotine dependence.Mayo Clin Proc. 2001; 76: 124-133PubMed Google Scholar In patients who continue to smoke, TAO is relentlessly progressive and results in chronic and severe pain, gangrene, and autoamputation. Urinary tobacco alkaloids should be measured in patients with TAO who deny smoking to detect surreptitious smoking. Aggressive tobacco dependence treatment, including residential treatment, should be offered to patients with this disease as soon as possible. Urinary Tobacco Alkaloid Measurement in Patients Having Thromboangiitis Obliterans–Reply–IMayo Clinic ProceedingsVol. 83Issue 10PreviewWe appreciate the insightful points made by Hurt and Hays. We agree that diagnostic studies of tobacco use would augment the evaluation of TAO and could prove particularly helpful in cases such as the one we presented, in which tobacco use was initially denied. In our case, angiography was required for the diagnosis of TAO; when the patient was presented with the angiographic findings while his mother was absent, he admitted to ongoing tobacco use. Urinary tobacco alkaloids might well be of benefit for assessing smoking cessation at subsequent follow-up visits for this patient. Full-Text PDF

Urinary Tobacco Alkaloid Measurement in Patients Having Thromboangiitis Obliterans–Reply–I

Urinary Tobacco Alkaloid Measurement in Patients Having Thromboangiitis Obliterans–Reply–I