No abstract

Background: Quitlines have become an integral part of tobacco control efforts in the United States and Canada. The demonstrated efficacy and the convenience of telephone based counselling have led to the fast adoption of quitlines, to the point of near universal access in North America. However, information on how these quitlines operate in actual practice is not often readily available. Objectives: This study describes quitline practice in North America and examines commonalities and differences across quitlines. It will serve as a source of reference for practitioners and researchers, with the aim of furthering service quality and promoting continued innovation. Design: A self administered questionnaire survey of large, publicly funded quitlines in the United States and Canada. A total of 52 US quitlines and 10 Canadian quitlines participated. Descriptive statistics are provided regarding quitline operational structures, clinical services, quality assurance procedures, funding sources and utilisation rates. Results: Clinical services for the 62 state/provincial quitlines are supplied by a total of 26 service providers. Nine providers operate multiple quitlines, creating greater consistency in operation than would otherwise be expected. Most quitlines offer services over extended hours (mean 96 hours/week) and have multiple language capabilities. Most (98%) use proactive multisession counselling-a key feature of protocols tested in previous experimental trials. Almost all quitlines have extensive training programmes (.60 hours) for counselling staff, and over 70% conduct regular evaluation of outcomes. About half of quitlines use the internet to provide cessation information. A little over a third of US quitlines distribute free cessation medications to eligible callers. The average utilisation rate of the US state quitlines in the 2004-5 fiscal year was about 1.0% across states, with a strong correlation between the funding level of the quitlines and the smokers' utilisation of them (r = 0.74, p,0.001). Conclusions: Quitlines in North America display core commonalities: they have adopted the principles of multisession proactive counselling and they conduct regular outcome evaluation. Yet variations, tested and untested, exist. Standardised reporting procedures would be of benefit to the field. Shared discussion of the rationale behind variations can inform future decision making for all North American quitlines.

Objective: To explore determinants of support for and reported compliance with smoke-free policies in restaurants and bars across the four countries of the International Tobacco Control (ITC) Four Country Survey. Design: Separate telephone cross-sectional surveys conducted between October and December 2002 with broadly representative samples of over 2000 adult (greater than or equal to 18 years) cigarette smokers in each of the following four countries: the United States, Canada, the United Kingdom, and Australia. Outcome measures: Support for smoke-free policies in restaurants and pubs/bars and reported compliance with existing policies. Results: Reported total bans on indoor smoking in restaurants varied from 62% in Australia to 5% in the UK. Smoking bans in bars were less common, with California in the USA being the only major part of any country with documented bans. Support for bans in both restaurants and bars was related to the existence of bans, beliefs about passive smoking being harmful, lower average cigarette consumption, and older age. Self-reported compliance with a smoking ban was generally high and was associated with greater support for the ban. Conclusions: Among current cigarette smokers, support for smoking bans was associated with living in a place where the law prohibits smoking. Smokers adjust and both accept and comply with smoke-free laws. Associates of support and compliance are remarkably similar across countries given the notably different levels of smoke-free policies

Ibogaine, a hallucinogenic alkaloid with purported anti-addiction properties, inhibited serotonin transporter (SERT) noncompetitively by decreasing V max with little change in the K m for serotonin (5-HT). Ibogaine also inhibited binding to SERT of the cocaine analog 2␤-2-carbomethoxy-3-(4-[ 125 I]iodophenyl)tropane. However, inhibition of binding was competitive, increasing the apparent K D without much change in B max . Ibogaine increased the reactivity of cysteine residues positioned in the proposed cytoplasmic permeation pathway of SERT but not at nearby positions out of that pathway. In contrast, cysteines placed at positions in the extracellular permeation pathway reacted at slower rates in the presence of ibogaine. These results are consistent with the proposal that ibogaine binds to and stabilizes the state of SERT from which 5-HT dissociates to the cytoplasm, in contrast with cocaine, which stabilizes the state that binds extracellular 5-HT.Ibogaine is a hallucinogenic alkaloid found in the roots of the West African shrub Tabernanthe iboga. In Europe and North America, ibogaine has been promoted as a treatment for addiction, although clinical evidence has been difficult to obtain, partly due to its listing as a Schedule I controlled substance (1, 2) and partly due to concerns about toxicity (3). Ibogaine has affinity for 2 receptors, N-methyl-D-aspartate receptors, -opioid receptors, and serotonin and dopamine transporters (4 -7). Ibogaine is demethylated to 12-hydroxyibogamine (noribogaine), which has been reported to persist in the blood for over 24 h and to have even higher affinity for 5-HT transporters than ibogaine (8).The 5-hydroxytryptamine (5-HT) 3 transporter (SERT) is responsible for reuptake of 5-HT released from serotonergic neurons (9). This protein is the target for antidepressant drugs, such as imipramine and fluoxetine, and psychostimulants, such as cocaine and 3,4-methylenedioxymethamphetamine. SERT couples the entry of 5-HT into the cell to the entry of Na ϩ and Cl Ϫ and the exit of K ϩ (10). The transport of 5-HT has been envisaged as a two-step process, where 5-HT, Na ϩ , and Cl Ϫ are transported in a single step and K ϩ is transported in a second step (11). These transport steps are proposed to interconvert two states of the transporter: an extracellular state that binds extracellular substrates and a cytoplasmic state that releases those substrates to the cytoplasm (9).SERT belongs to a large family of Na ϩ -dependent transporters in prokaryotes and animals designated the SLC6 or NSS family. The high resolution x-ray structure of the prokaryotic leucine transporter LeuT (12) appears to be a good model for other members of the family, and homology models for SERT and other neurotransmitter transporters have been generated using structure-based alignments (13). The utility of LeuT as a model for SERT has recently been validated by the identification of the Cl Ϫ binding site in SERT through analysis of the LeuT structure (14). This structure shows an aqueous pathway leading from the ...

ABSTRACT:The present study examined the interaction of four 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (atorvastatin, lovastatin, and simvastatin in acid and lactone forms, and pravastatin in acid form only) with multidrug resistance gene 1 (MDR1, ABCB1) P-glycoprotein, multidrug resistance-associated protein 2 (MRP2, ABCC2), and organic anion-transporting polypeptide 1B1 (OATP1B1, SLCO21A6). P-glycoprotein substrate assays were performed using Madin-Darby canine kidney (MDCK) cells expressing MDR1, and the efflux ratios [the ratio of the ratio of basolateralto-apical apparent permeability and apical-to-basolateral permeability between MDR1 and MDCK] were 1.87, 2.32/4.46, 2.17/3.17, and 0.93/2.00 for pravastatin, atorvastatin (lactone/acid), lovastatin (lactone/acid), and simvastatin (lactone/acid), respectively, indicating that these compounds are weak or moderate substrates of P-glycoprotein. In the inhibition assays (MDR1, MRP2, Mrp2, and OATP1B1), the IC 50 values for efflux transporters (MDR1, MRP2, and Mrp2) were >100 M for all statins in acid form except lovastatin acid (>33 M), and the IC 50 values were up to 10-fold lower for the corresponding lactone forms. In contrast, the IC 50 values for the uptake transporter OATP1B1 were 3-to 7-fold lower for statins in the acid form compared with the corresponding lactone form. These data demonstrate that lactone and acid forms of statins exhibit differential substrate and inhibitor activities toward efflux and uptake transporters. The interconversion between the lactone and acid forms of most statins exists in the body and will potentially influence drug-transporter interactions, and may ultimately contribute to the differences in pharmacokinetic profiles observed between statins.