New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Production of Biogenic Mn Oxides by \u3cem\u3eLeptothrix discophora\u3c/em\u3e SS-1 in a Chemically Defined Growth Medium and Evaluation of Their Pb Adsorption Characteristics

Biogenic Mn oxides were produced by the bacterium Leptothrix discophora SS-1 (= ATCC 3182) in a chemically defined mineral salts medium, and the Pb binding and specific surface area of these oxides were characterized. Growth of SS-1 in the defined medium with pyruvate as a carbon and energy source required the addition of vitamin B12. Complete oxidation of Mn(II) within 60 h required the addition of ≥0.1 μM FeSO4. Pb adsorption isotherms were determined for the biogenic Mn oxides (and associated cells with their extracellular polymer) and compared to the Pb adsorption isotherms of cells and exopolymer alone, as well as to abiotic Mn oxides. The Pb adsorption to cells and exopolymer with biogenic Mn oxides (0.8 mmol of Mn per g) at pH 6.0 and 25°C was 2 orders of magnitude greater than the Pb adsorption to cells and exopolymer alone (on a dry weight basis). The Pb adsorption to the biogenic Mn oxide was two to five times greater than the Pb adsorption to a chemically precipitated abiotic Mn oxide and several orders of magnitude greater than the Pb adsorption to two commercially available crystalline MnO2 minerals. The N2 Brunauer-Emmet-Teller specific surface areas of the biogenic Mn oxide and fresh Mn oxide precipitate (224 and 58 m2/g, respectively) were significantly greater than those of the commercial Mn oxide minerals (0.048 and 4.7 m2/g). The Pb adsorption capacity of the biogenic Mn oxide also exceeded that of a chemically precipitated colloidal hydrous Fe oxide under similar solution conditions. These results show that amorphous biogenic Mn oxides similar to those produced by SS-1 may play a significant role in the control of trace metal phase distribution in aquatic systems

Determination of Iron Colloid Size Distribution in the Presence of Suspended Cells: Application to Iron Deposition onto a Biofilm Surface

Transport and deposition of colloidal Fe, Mn and Al oxides play key roles in the cycling of toxic transition metals in aquatic environments because these colloids strongly bind transition metals. Further, attachment of biological cells and biofilm growth on surfaces can indirectly affect toxic metal distribution by influencing the deposition of colloidal oxides to surfaces. To elucidate the mechanisms governing these processes, deposition of colloidal oxides onto surfaces must be evaluated in the presence of suspended and adherent bacterial cells. Both particle size and concentration are expected to influence deposition. An experimental protocol was developed to determine the size distribution of iron colloids in mixtures with suspended cells. A Ti(III) reagent was used to reduce and dissolve colloidal Fe(III) from mixtures containing both suspended cells and Fe colloids. The size distribution of Fe(III) colloids in the original solution was then determined from the difference between size distributions before and after dissolution of Fe with Ti(III). The Ti(III) reagent dissolved over 95% of the Fe colloids without altering the size distribution of suspended bacterial cells, and the method accurately determined the size distribution of Fe colloids added to cell suspensions. The applicability of this protocol was tested by applying it to a study of the deposition of Fe(III) oxide particles onto glass surfaces with and without biofilms of the bacterium Burkholdaria cepacia 17616. Experimental results using a laboratory biofilm reactor indicated that the deposition rate of Fe(III) colloids was not significantly affected by the presence of B. cepacia biofilms or by the presence of previously deposited Fe. However, deposition of Fe to reactor surfaces other than the glass surfaces may have interfered with the analyses, and atomic absorption measurements showed a slight increase in Fe deposition onto glass surfaces with biofilms present. Fe deposition to the composite of all reactor surfaces increased with increasing colloidal particle size, indicating a dominance of interception and/or sedimentation in controlling Fe deposition on surfaces in the biofilm reactor

Kinetics of Mn(II) oxidation by Leptothrix discophora SS1

The kinetics of Mn(II) oxidation by the bacterium Leptothrix discophora SS1 was investigated in this research. Cells were grown in a minimal mineral salts medium in which chemical speciation was well defined. Mn(II) oxidation was observed in a bioreactor under controlled conditions with pH, O\u3esub\u3e2, and temperature regulation. Mn(II) oxidation experiments were performed at cell concentrations between 24 mg/L and 35 mg/L, over a pH range from 6 to 8.5, between temperatures of 10°C and 40°C, over a dissolved oxygen range of 0 to 8.05 mg/L, and with L. discophora SS1 cells that were grown in the presence of Cu concentrations ranging from zero to 0.1 µM. Mn(II) oxidation rates were determined when the cultures grew to stationary phase and were found to be directly proportional to O2 and cell concentrations over the ranges investigated. The optimum pH for Mn(II) oxidation was approximately 7.5, and the optimum temperature was 30°C. A Cu level as low as 0.02 µM was found to inhibit the growth rate and yield of L. discophora SS1 observed in shake flasks, while Cu levels between 0.02 and 0.1 µM stimulated the Mn(II) oxidation rate observed in bioreactors. An overall rate law for Mn(II) oxidation by L. discophora as a function of pH, temperature, dissolved oxygen concentration (D.O.), and Cu concentration is proposed. At circumneutral pH, the rate of biologically mediated Mn(II) oxidation is likely to exceed homogeneous abiotic Mn(II) oxidation at relatively low (≈µg/L) concentrations of Mn oxidizing bacteria

Adsorption of Pb and Cd Onto Metal Oxides and Organic Material in Natural Surface Coatings as Determined by Selective Extractions: New Evidence for the Importance of Mn and Fe Oxides

Surface coatings (biofilms and associated minerals) were collected on glass slides in the toxic surface waters of Cayuga Lake (New York State, U.S.A.) and were used to evaluate the relative contributions of Fe, Mn and Al oxides and organic material to total observed Pb and Cd adsorption by the surface coating materials. Several alternative selective extraction techniques were evaluated with respect to both selectivity and alteration of the residual unextracted material. Pb and Cd adsorption was measured under controlled laboratory conditions (mineral salts solution with defined metal speciation, ionic strength 0.05 M, 25°C and pH 6.0) before and after extractions to determine by difference the adsorptive properties of the extracted component(s). Hydroxylamine hydrochloride (0.01 M NH2OH·HCl+0.01 M HNO3) was used to selectively remove Mn oxides, sodium dithionite (0.3 M Na2S2O4) was used to remove Mn and Fe oxides, and 10% oxalic acid was used to remove metal oxides and organic materials. Several other extractants were evaluated, but preliminary experiments indicated that they were not suitable for these experiments because of undesirable alterations of the residual, unextracted material. The selected extraction methods removed target components with efficiencies between 71 and 83%, but significant amounts of metal oxides and organic materials other than the target components were also removed by the extractants (up to 39%). Nonlinear regression analysis of the observed Pb and Cd adsorption based on the assumption of additive Langmuir adsorption isotherms was used to estimate the relative contributions of each surface coating constituent to total Pb and Cd binding of the biofilms. Adsorption of Cd to the lake biofilms was dominated by Fe oxides, with lesser roles attributed to adsorption by Mn and Al oxides and organic material. Adsorption of Pb was dominated by Mn oxides, with lesser roles indicated for adsorption to Fe oxides and organic material, and the estimated contribution of Al oxides to Pb adsorption was insignificant. The fitted Pb adsorption isotherm for Fe oxides was in excellent agreement with those obtained through direct experiments and reported in independent investigations. The estimated Pb distribution between surface coating components also agreed well with that previously predicted by an additive adsorption model based on Pb adsorption isotherms for laboratory surrogates for Mn, Fe and Al oxides and defined biological components