Rhodococcus Strains from the Specialized Collection of Alkanotrophs for Biodegradation of Aromatic Compounds.

The ability to degrade aromatic hydrocarbons, including (i) benzene, toluene, o-xylene, naphthalene, anthracene, phenanthrene, benzo[a]anthracene, and benzo[a]pyrene; (ii) polar substituted derivatives of benzene, including phenol and aniline; (iii) N-heterocyclic compounds, including pyridine; 2-, 3-, and 4-picolines; 2- and 6-lutidine; 2- and 4-hydroxypyridines; (iv) derivatives of aromatic acids, including coumarin, of 133 Rhodococcus strains from the Regional Specialized Collection of Alkanotrophic Microorganisms was demonstrated. The minimal inhibitory concentrations of these aromatic compounds for Rhodococcus varied in a wide range from 0.2 up to 50.0 mM. o-Xylene and polycyclic aromatic hydrocarbons (PAHs) were the less-toxic and preferred aromatic growth substrates. Rhodococcus bacteria introduced into the PAH-contaminated model soil resulted in a 43% removal of PAHs at an initial concentration 1 g/kg within 213 days, which was three times higher than that in the control soil. As a result of the analysis of biodegradation genes, metabolic pathways for aromatic hydrocarbons, phenol, and nitrogen-containing aromatic compounds in Rhodococcus, proceeding through the formation of catechol as a key metabolite with its following ortho-cleavage or via the hydrogenation of aromatic rings, were verified.

Bupropion Slow Release vs Placebo With Adaptive Incentives for Cocaine Use Disorder in Persons Receiving Methadone for Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Opioid-stimulant co-use is a common problem with few evidence-based treatments. Objective: To examine bupropion slow release (SR) enhancement of a tailored abstinence incentive program for stimulant use in persons with opioid use disorder. Design, Setting, and Participants: This 26-week, double-blind, placebo-controlled randomized clinical trial with a 4-week follow-up period was conducted at 4 methadone treatment programs in Baltimore, Maryland. Included participants were persons receiving methadone for the treatment of opioid use disorder with past 3-month cocaine use and current cocaine use disorder between March 2015 and September 2019. Data were analyzed from November 2020 through August 2022. Interventions: A 6-week incentive induction period with monetary incentives for evidence of cocaine abstinence during thrice-weekly urine testing was conducted. Persons achieving 2 weeks of consecutive abstinence during induction were assigned to the relapse prevention group (20 individuals); otherwise, individuals were assigned to the abstinence initiation group (60 individuals). Participants were randomized within incentive groups to bupropion SR (150 mg oral twice daily; 40 participants) or placebo (40 participants). Incentives were available until week 26, and study medication ended week 30. Main Outcomes and Measures: The mean percentage of participants with cocaine abstinence (by negative urinalysis or self-report) during weeks 7 to 26 (ie, the incentive intervention period) and 27 to 30 (ie, the follow-up period) and the percentage of participants testing negative for cocaine at weeks 26 and 30 were assessed. Main effects of medication collapsed across incentive conditions and sensitivity analyses of medications within incentive conditions were assessed. Analyses were conducted in the modified intention-to-treat sample (ie, 80 individuals who received ≥1 dose of study medication) and completers (ie, 52 individuals who completed ≥1 visit during week 30). Results: Among 80 participants (42 Black [52.5% ] and 35 White [43.8%]; mean [SD] age, 45.7 (9.4) years; 52 males [65.0%]) receiving methadone for opioid use disorder, 40 participants were randomized to receive bupropion SR and 40 participants to receive placebo. No significant difference on urinalysis or self-reported cocaine use was observed between medication groups. Sensitivity analyses revealed differential patterns for incentive subgroups. Participants in the relapse prevention group had high abstinence (>80%; eg, during weeks 7-26 in the modified intention-to-treat analysis, 410 of 456 samples [89.9%] from participants in the bupropion SR group tested negative for cocaine) throughout the trial regardless of whether they were randomized to bupropion SR or placebo. Participants in the abstinence initiation group had better outcomes with bupropion SR than placebo throughout the trial (mean [SD] total number of samples testing negative for cocaine, 30.3 [21.6] samples for bupropion SR vs 17.1 [14.9] samples for placebo; P = .05) and more participants receiving bupropion SR than placebo were abstinent at the end of the study (20 of 30 participants [66.7%] vs 9 of 30 participants [30.0%]; P = .04). Conclusions and Relevance: In this randomized clinical trial, an overall benefit for bupropion SR vs placebo when combined with a financial abstinence incentive program was not observed. Results among incentive subgroups suggest that continued evaluation of medications, including bupropion SR, for stimulant treatment using a tailored approach that factors early abstinence into study design and interpretation may be needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02111798.

Mouth Level Intake of Nicotine from Three Brands of Little Filtered Cigars with Widely Differing Product Characteristics Among Adult Consumers.

Little filtered cigars are tobacco products with many cigarette-like characteristics. However, despite cigars falling under the U.S. Food and Drug Administration regulatory authority, characterizing flavors, which are still allowed in little filtered cigars, and filter design may influence how people use the products and the resulting exposure to harmful and potentially harmful constituents. We estimated nicotine mouth level intake (MLI) from analyses of little cigar filter butt solanesol levels, brand characteristics, carbon monoxide boost, and puff volume in 48 dual cigarette/cigar users during two repeat bouts of ad lib smoking of three little filtered cigar brands. Mean nicotine MLI for the three brands was significantly different with Swisher Sweets (0.1% ventilation) Cherry at 1.20 mg nicotine, Cheyenne Menthol (1.5%) at 0.63 mg, and Santa Fe unflavored (49%) at 0.94 mg. The association between nicotine MLI and puff volume was the same between Cheyenne Menthol and Santa Fe unflavored. However, these were different from Swisher Sweets Cherry. At least five main factors─flavor, ventilation, filter design, nicotine delivery related to tar, and user puff volume─may directly or indirectly impact MLI and its association with other measures. We found that users of little filtered cigars that have different filter ventilation and flavor draw dissimilar amounts of nicotine from the product, which may be accompanied by differences in exposure to other harmful smoke constituents.

Symptoms of tobacco dependence among middle and high school tobacco users - Data from the 2019-2020 National Youth Tobacco Survey.

INTRODUCTION: Previous studies have indicated that youth who use tobacco products, including cigarettes, cigars, and smokeless tobacco, demonstrate dependence symptoms. However, the tobacco marketplace has expanded dramatically in recent years, and few studies have examined dependence symptoms among youth who use novel products. This study combined 2019-2020 National Youth Tobacco Survey data to report the prevalence and determinants of tobacco dependence symptoms among U.S. middle and high school current (past 30-day) tobacco users. METHODS: Prevalence estimates were calculated to examine dependence outcomes and other covariates by user groups (single product users and multiple product users). Multivariable logistic regression analyses were used to identify independent predictors of tobacco dependence among current users of cigarettes, cigars (regular cigars, cigarillos, and little cigars), e-cigarettes, heated tobacco products, hookah, pipe tobacco, bidis, and smokeless tobacco products (chew, snuff, dip, snus, and dissolvables). RESULTS: Among current tobacco users, 15.7 % (95 % CI: 14.2-17.3) reported wanting to use tobacco within 30 min of waking and 28.3 % (95 % CI: 26.3-30.5) reported strong cravings for tobacco in the past 30 days. Nearly-two-thirds of current users were single product users, of which 80.5 % reported using e-cigarettes. Reporting of dependence symptoms was generally associated with multiple product use, higher frequency of use, earlier initiation age, and use of flavored products. CONCLUSIONS: Among U.S. adolescents, a considerable amount of current tobacco product users, even infrequent users, reported symptoms of dependence. These findings highlight the continued importance of prevention strategies for youth tobacco experimentation and progression to regular use.

Adhesion of Rhodococcus bacteria to solid hydrocarbons and enhanced biodegradation of these compounds.

Adhesive activities of hydrocarbon-oxidizing Rhodococcus bacteria towards solid hydrocarbons, effects of adhesion on biodegradation of these compounds by rhodococcal cells and adhesion mechanisms of Rhodococcus spp. were studied in this work. It was shown that efficiency of Rhodococcus cells' adhesion to solid n-alkanes and polycyclic aromatic hydrocarbons (PAHs) varied from 0.0 to 10.6·106 CFU/cm2. R. erythropolis IEGM 212 and R. opacus IEGM 262 demonstrated the highest (≥ 4.3·106 CFU/cm2) adhesion. The percentage biodegradation of solid hydrocarbons (n-hexacosane and anthracene as model substrates) by Rhodococcus cells was 5 to 60% at a hydrocarbon concentration of 0.2% (w/w) after 9 days and strongly depended on cell adhesive activities towards these compounds (r ≥ 0.71, p < 0.05). No strict correlation between the adhesive activities of rhodococcal cells and physicochemical properties of bacteria and hydrocarbons was detected. Roughness of the cell surface was a definitive factor of Rhodococcus cell adhesion to solid hydrocarbons. Specific appendages with high adhesion force (≥ 0.6 nN) and elastic modulus (≥ 6 MPa) were found on the surface of Rhodococcus cells with high surface roughness. We hypothesized that these appendages participated in the adhesion process.

Potential risks of antibiotic resistant bacteria and genes in bioremediation of petroleum hydrocarbon contaminated soils.

Bioremediation represents a sustainable approach to remediating petroleum hydrocarbon contaminated soils. One aspect of sustainability includes the sourcing of nutrients used to stimulate hydrocarbon-degrading microbial populations. Organic nutrients such as animal manure and sewage sludge may be perceived as more sustainable than conventional inorganic fertilizers. However, organic nutrients often contain antibiotic residues and resistant bacteria (along with resistance genes and mobile genetic elements). This is further exacerbated since antibiotic resistant bacteria may become more abundant in contaminated soils due to co-selection pressures from pollutants such as metals and hydrocarbons. We review the issues surrounding bioremediation of petroleum-hydrocarbon contaminated soils, as an example, and consider the potential human-health risks from antibiotic resistant bacteria. While awareness is coming to light, the relationship between contaminated land and antibiotic resistance remains largely under-explored. The risk of horizontal gene transfer between soil microorganisms, commensal bacteria and/or human pathogens needs to be further elucidated, and the environmental triggers for gene transfer need to be better understood. Findings of antibiotic resistance from animal manures are emerging, but even fewer bioremediation studies using sewage sludge have made any reference to antibiotic resistance. Resistance mechanisms, including those to antibiotics, have been considered by some authors to be a positive trait associated with resilience in strains intended for bioremediation. Nevertheless, recognition of the potential risks associated with antibiotic resistant bacteria and genes in contaminated soils appears to be increasing and requires further investigation. Careful selection of bacterial candidates for bioremediation possessing minimal antibiotic resistance as well as pre-treatment of organic wastes to reduce selective pressures (e.g., antibiotic residues) are suggested to prevent environmental contamination with antibiotic-resistant bacteria and genes.

Discriminative stimulus effects of mecamylamine and nicotine in rhesus monkeys: Central and peripheral mechanisms.

Mecamylamine is a non-competitive nicotinic acetylcholine receptor (nAChR) antagonist that has been prescribed for hypertension and as an off-label smoking cessation aid. Here, we examined pharmacological mechanisms underlying the interoceptive effects (i.e., discriminative stimulus effects) of mecamylamine (5.6 mg/kg s.c.) and compared the effects of nAChR antagonists in this discrimination assay to their capacity to block a nicotine discriminative stimulus (1.78 mg/kg s.c.) in rhesus monkeys. Central (pempidine) and peripherally restricted nAChR antagonists (pentolinium and chlorisondamine) dose-dependently substituted for the mecamylamine discriminative stimulus in the following rank order potency (pentolinium > pempidine > chlorisondamine > mecamylamine). In contrast, at equi-effective doses based on substitution for mecamylamine, only mecamylamine antagonized the discriminative stimulus effects of nicotine, i.e., pentolinium, chlorisondamine, and pempidine did not. NMDA receptor antagonists produced dose-dependent substitution for mecamylamine with the following rank order potency (MK-801 > phencyclidine > ketamine). In contrast, behaviorally active doses of smoking cessation aids including nAChR agonists (nicotine, varenicline, and cytisine), the smoking cessation aid and antidepressant bupropion, and the benzodiazepine midazolam did not substitute for the discriminative stimulus effects of mecamylamine. These data suggest that peripheral nAChRs and NMDA receptors may contribute to the interoceptive stimulus effects produced by mecamylamine. Based on the current results, the therapeutic use of mecamylamine (i.e., for smoking or to alleviate green tobacco sickness) should be weighed against the potential for mecamylamine to produce interoceptive effects that overlap with another class of abused drugs (i.e., NMDA receptor agonists).

Enhancing patient navigation to improve intervention session attendance and viral load suppression of persons with HIV and substance use: a secondary post hoc analysis of the Project HOPE study.

BACKGROUND: Interventions are needed to improve viral suppression rates among persons with HIV and substance use. A 3-arm randomized multi-site study (Metsch et al. in JAMA 316:156-70, 2016) was conducted to evaluate the effect on HIV outcomes of usual care referral to HIV and substance use services (N = 253) versus patient navigation delivered alone (PN: N = 266) or together with contingency management (PN + CM; N = 271) that provided financial incentives targeting potential behavioral mediators of viral load suppression. AIMS: This secondary analysis evaluates the effects of financial incentives on attendance at PN sessions and the relationship between session attendance and viral load suppression at end of the intervention. METHODS: Frequency of sessions attended was analyzed over time and by distribution of individual session attendance frequency (PN vs PN + CM). Percent virally suppressed (≤200 copies/mL) at 6 months was compared for low, medium and high rate attenders. In PN + CM a total of $220 could be earned for attendance at 11 PN sessions over the 6-month intervention with payments ranging from $10 to $30 under an escalating schedule. RESULTS: The majority (74%) of PN-only participants attended 6 or more sessions but only 28% attended 10 or more and 16% attended all eleven sessions. In contrast, 90% of PN + CM attended 6 or more visits, 69% attended 10 or more and 57% attended all eleven sessions (attendance distribution χ2[11] = 105.81; p < .0001). Overall (PN and PN + CM participants combined) percent with viral load suppression at 6-months was 15, 38 and 54% among those who attended 0-5, 6-9 and 10-11 visits, respectively (χ2(2) = 39.07, p < .001). CONCLUSION: In this secondary post hoc analysis, contact with patient navigators was increased by attendance incentives. Higher rates of attendance at patient navigation sessions was associated with viral suppression at the 6-month follow-up assessment. Study results support use of attendance incentives to improve rates of contact between service providers and patients, particularly patients who are difficult to engage in care. Trial Registration clinicaltrials.govIdentifier: NCT01612169.

Contingency Management Abstinence Incentives: Cost and Implications for Treatment Tailoring.

OBJECTIVE: To examine prize-earning costs of contingency management (CM) incentives in relation to participants' pre-study enrollment drug use status (baseline (BL) positive vs. BL negative) and relate these to previously reported patterns of intervention effectiveness. METHODS: Participants were 255 substance users entering outpatient treatment who received the therapeutic educational system (TES), in addition to usual care counseling. TES included a CM component such that participants could earn up to $600 in prizes on average over 12-weeks for providing drug negative urines and completing web-based cognitive behavior therapy modules. We examined distribution of prize draws and value of prizes earned for subgroups that were abstinent (BL negative; N=136) or not (BL positive; N=119) at study entry based on urine toxicology and breath alcohol screen. RESULTS: Distribution of draws earned (median=119 vs. 17; p<.0001) and prizes redeemed (median=54 vs. 9; p<.001) for drug abstinence differed significantly for BL negative compared to BL positive participants. BL negative earned on average twice as much in prizes as BL positive participants ($245 vs. $125). Median value of prizes earned was 5.4 times greater for BL negative compared to BL positive participants ($237 vs. $44; p<.001). CONCLUSIONS: Two-thirds of expenditures in an abstinence incentive program were paid to BL negative participants. These individuals had high rates of drug abstinence during treatment and did not show improved abstinence outcomes with TES versus usual care (Campbell et al., 2014). Effectiveness of the abstinence-focused CM intervention included in TES may be enhanced by tailoring delivery based on patients' drug use status at treatment entry.

Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily.

BACKGROUND AND PURPOSE: Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. EXPERIMENTAL APPROACH: The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg-1 base weight) from saline. One group received additional nicotine treatment post-session (1.78 mg·kg-1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). KEY RESULTS: Daily repeated nicotine treatment produced a time-related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro-ß-erythroidine did not. Midazolam produced 0% nicotine-lever responding. The nAChR agonists epibatidine, RTI-36, cytisine and varenicline produced >96% nicotine-lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine-like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. CONCLUSION AND IMPLICATIONS: Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes.

Removal of polycyclic aromatic hydrocarbons in soil spiked with model mixtures of petroleum hydrocarbons and heterocycles using biosurfactants from Rhodococcus ruber IEGM 231.

Removal of polycyclic aromatic hydrocarbons (PAHs) in soil using biosurfactants (BS) produced by Rhodococcus ruber IEGM 231 was studied in soil columns spiked with model mixtures of major petroleum constituents. A crystalline mixture of single PAHs (0.63g/kg), a crystalline mixture of PAHs (0.63g/kg) and polycyclic aromatic sulfur heterocycles (PASHs), and an artificially synthesized non-aqueous phase liquid (NAPL) containing PAHs (3.00g/kg) dissolved in alkanes C10-C19 were used for spiking. Percentage of PAH removal with BS varied from 16 to 69%. Washing activities of BS were 2.5 times greater than those of synthetic surfactant Tween 60 in NAPL-spiked soil and similar to Tween 60 in crystalline-spiked soil. At the same time, amounts of removed PAHs were equal and consisted of 0.3-0.5g/kg dry soil regardless the chemical pattern of a model mixture of petroleum hydrocarbons and heterocycles used for spiking. UV spectra for soil before and after BS treatment were obtained and their applicability for differentiated analysis of PAH and PASH concentration changes in remediated soil was shown. The ratios A254nm/A288nm revealed that BS increased biotreatability of PAH-contaminated soils.

Oil spill problems and sustainable response strategies through new technologies.

Crude oil and petroleum products are widespread water and soil pollutants resulting from marine and terrestrial spillages. International statistics of oil spill sizes for all incidents indicate that the majority of oil spills are small (less than 7 tonnes). The major accidents that happen in the oil industry contribute only a small fraction of the total oil which enters the environment. However, the nature of accidental releases is that they highly pollute small areas and have the potential to devastate the biota locally. There are several routes by which oil can get back to humans from accidental spills, e.g. through accumulation in fish and shellfish, through consumption of contaminated groundwater. Although advances have been made in the prevention of accidents, this does not apply in all countries, and by the random nature of oil spill events, total prevention is not feasible. Therefore, considerable world-wide effort has gone into strategies for minimising accidental spills and the design of new remedial technologies. This paper summarizes new knowledge as well as research and technology gaps essential for developing appropriate decision-making tools in actual spill scenarios. Since oil exploration is being driven into deeper waters and more remote, fragile environments, the risk of future accidents becomes much higher. The innovative safety and accident prevention approaches summarized in this paper are currently important for a range of stakeholders, including the oil industry, the scientific community and the public. Ultimately an integrated approach to prevention and remediation that accelerates an early warning protocol in the event of a spill would get the most appropriate technology selected and implemented as early as possible - the first few hours after a spill are crucial to the outcome of the remedial effort. A particular focus is made on bioremediation as environmentally harmless, cost-effective and relatively inexpensive technology. Greater penetration into the remedial technologies market depends on the harmonization of environment legislation and the application of modern laboratory techniques, e.g. ecogenomics, to improve the predictability of bioremediation.

The discriminative stimulus effects of mecamylamine in nicotine-treated and untreated rhesus monkeys.

The extent to which chronic nicotine treatment can alter the effects of the nicotinic acetylcholine receptor antagonist mecamylamine, and whether those effects can be attenuated by nicotine have not been clearly established in the literature. Here, the discriminative stimulus effects of mecamylamine were compared between one group of rhesus monkeys receiving a continuous infusion of nicotine base (5.6 mg/kg/day subcutaneously) and another group of monkeys not receiving nicotine treatment. Both groups responded under a fixed ratio 5 schedule of stimulus-shock termination. Stimulus control was obtained at doses of 1.78 mg/kg mecamylamine in monkeys receiving continuous nicotine and 5.6 mg/kg mecamylamine in monkeys not receiving continuous nicotine treatment. Nicotine did not attenuate the discriminative stimulus effects of mecamylamine in either group. Discontinuation of continuous nicotine produced responding on the mecamylamine lever within 24 h in some but not all monkeys. This may indicate a qualitative difference in the discriminative stimulus effects of mecamylamine between groups, perhaps reflecting antagonism of nicotine and nicotine withdrawal in monkeys receiving continuous nicotine. The failure of nicotine to reverse the effects of mecamylamine is consistent with a noncompetitive interaction at nicotinic acetylcholine receptors and indicates that mecamylamine-induced withdrawal cannot be readily modified by nicotine.

Discriminative stimulus and hypothermic effects of some derivatives of the nAChR agonist epibatidine in mice.

RATIONALE: Receptor mechanisms underlying the in vivo effects of nicotinic acetylcholine receptor (nAChR) drugs need to be determined to better understand possible differences in therapeutic potential. OBJECTIVE: This study compared the effects of agonists that are reported either to differ in intrinsic activity (i.e., efficacy) at α4ß2 nAChR in vitro or to have in vivo effects consistent with differences in efficacy. The drugs included nicotine, varenicline, cytisine, epibatidine, and three novel epibatidine derivatives: 2'-fluoro-3'-(4-nitrophenyl)deschloroepibatidine (RTI-7527-102), 2'-fluorodeschloroepibatidine (RTI-7527-36), and 3'-(3″-dimethylaminophenyl)-epibatidine (RTI-7527-76). METHODS: Mice discriminated nicotine base (1 mg/kg base) from saline; other mice were used to measure rectal temperature. RESULTS: In the nicotine discrimination assay, the maximum percentage of nicotine-appropriate responding varied: 92 % for nicotine, 84 % for epibatidine, 77 % for RTI-7527-36, and 71 % for varenicline and significantly less for RTI-7527-76 (58 %), RTI-7527-102 (46 %), and cytisine (33 %). Each drug markedly decreased rectal temperature by as much as 12 ºC. The rank-order potency in the discrimination and hypothermia assays was epibatidine > RTI-7527-36 > nicotine > RTI-7527-102 > varenicline = cytisine = RTI-7527-76. The nAChR antagonist mecamylamine (3.2 mg/kg) antagonized the discriminative stimulus effects of epibatidine and RTI-7527-102, as well as the hypothermic effects of every drug except cytisine. The ß2-subunit selective nAChR antagonist dihydro-ß-erythroidine (DHßE; up to 10 mg/kg) antagonized hypothermic effects but less effectively so than mecamylamine. CONCLUSIONS: The marked hypothermic effects of all drugs except cytisine are due in part to agonism at nAChR containing ß2-subunits. Differential substitution for the nicotine discriminative stimulus is consistent with differences in α4ß2 nAChR efficacy; however, collectively the current results suggest that multiple nAChR receptor subtypes mediate the effects of the agonists.

Field application of a rapid spectrophotometric method for determination of persulfate in soil.

Remediation of hydrocarbon contaminated soils can be performed both in situ and ex situ using chemical oxidants such as sodium persulfate. Standard methods for quantifying persulfate require either centrifugation or prolonged settling times. An optimized soil extraction procedure was developed for persulfate involving simple water extraction using a modified disposable syringe. This allows considerable saving of time and removes the need for centrifugation. The extraction time was reduced to only 5 min compared to 15 min for the standard approach. A comparison of the two approaches demonstrated that each provides comparable results. Comparisons were made using high (93 g kg(-1) soil) and low (9.3 g kg(-1) soil) additions of sodium persulfate to a petroleum hydrocarbon-contaminated soil, as well as sand spiked with diesel. Recoveries of 95±1% and 96±10% were observed with the higher application rate in the contaminated soil and spiked sand, respectively. Corresponding recoveries of 86±5% and 117±19% were measured for the lower application rate. Results were obtained in only 25 min and the method is well suited to batch analyses. In addition, it is suitable for application in a small field laboratory or even a mobile, vehicle-based system, as it requires minimal equipment and reagents.

Multiple nicotine training doses in mice as a basis for differentiating the effects of smoking cessation aids.

RATIONALE: Receptor mechanisms underlying the behavioral effects of clinically used nicotinic acetylcholine receptor agonists have not been fully established. OBJECTIVE: Drug discrimination was used to compare receptor mechanisms underlying the effects of smoking cessation aids. METHODS: Separate groups of male C57BL/6J mice discriminated 0.56, 1, or 1.78 mg/kg of nicotine base. Nicotine, varenicline, and cytisine were administered alone, in combination with each other, and in combination with mecamylamine and dihydro-ß-erythroidine (DHßE). Midazolam and morphine were tested to examine sensitivity to non-nicotinics. RESULTS: The ED50 value of nicotine to produce discriminative stimulus effects systematically increased as training dose increased. Varenicline and cytisine did not fully substitute for nicotine and, as compared with nicotine, their ED50 values varied less systematically as a function of nicotine training dose. Morphine did not substitute for nicotine, whereas midazolam substituted for the low and not the higher training doses of nicotine. As training dose increased, the dose of mecamylamine needed to produce a significant rightward shift in the nicotine dose-effect function also increased. DHßE antagonized nicotine in animals discriminating the smallest dose of nicotine. Varenicline did not antagonize the effects of nicotine, whereas cytisine produced a modest though significant antagonism of nicotine. CONCLUSIONS: These results suggest that differences in pharmacologic mechanism between nicotine, varenicline, and cytisine include not only differences in efficacy at a common subtype of nicotinic acetylcholine receptor, but also differential affinity and/or efficacy at multiple receptor subtypes.

Precision engineering for astronomy: historical origins and the future revolution in ground-based astronomy.

Since the dawn of civilization, the human race has pushed technology to the limit to study the heavens in ever-increasing detail. As astronomical instruments have evolved from those built by Tycho Brahe in the sixteenth century, through Galileo and Newton in the seventeenth, to the present day, astronomers have made ever more precise measurements. To do this, they have pushed the art and science of precision engineering to extremes. Some of the critical steps are described in the evolution of precision engineering from the first telescopes to the modern generation telescopes and ultra-sensitive instruments that need a combination of precision manufacturing, metrology and accurate positioning systems. In the future, precision-engineered technologies such as those emerging from the photonics industries may enable future progress in enhancing the capabilities of instruments, while potentially reducing the size and cost. In the modern era, there has been a revolution in astronomy leading to ever-increasing light-gathering capability. Today, the European Southern Observatory (ESO) is at the forefront of this revolution, building observatories on the ground that are set to transform our view of the universe. At an elevation of 5000 m in the Atacama Desert of northern Chile, the Atacama Large Millimetre/submillimetre Array (ALMA) is nearing completion. The ALMA is the most powerful radio observatory ever and is being built by a global partnership from Europe, North America and East Asia. In the optical/infrared part of the spectrum, the latest project for ESO is even more ambitious: the European Extremely Large Telescope, a giant 40 m class telescope that will also be located in Chile and which will give the most detailed view of the universe so far.

Pharmacologic characterization of a nicotine-discriminative stimulus in rhesus monkeys.

This study examined mechanisms by which nicotine (1.78 mg/kg base s.c.) produces discriminative stimulus effects in rhesus monkeys. In addition to nicotine, various test compounds were studied including other nicotinic acetylcholine receptor agonists (varenicline and cytisine), antagonists [mecamylamine and the α4ß2 receptor-selective antagonist dihydro-ß-erythroidine (DHßE)], a nicotinic acetylcholine receptor antagonist/indirect-acting catecholamine agonist (bupropion), and non-nicotinics (cocaine and midazolam). Nicotine, varenicline, and cytisine dose-dependently increased drug-lever responding; the ED(50) values were 0.47, 0.53, and 39 mg/kg, respectively. Bupropion and cocaine produced 100% nicotine-lever responding in a subset of monkeys, whereas mecamylamine, DHßE, and midazolam produced predominantly vehicle-lever responding. The training dose of nicotine resulted in 1128 ng/ml cotinine in saliva. Mecamylamine antagonized the discriminative stimulus effects of nicotine and varenicline, whereas DHßE was much less effective. Nicotine and varenicline had synergistic discriminative stimulus effects. In monkeys responding predominantly on the vehicle lever after a test compound (bupropion, cocaine, and midazolam), that test compound blocked the nicotine-discriminative stimulus, perhaps reflecting a perceptual-masking phenomenon. These results show that nicotine, varenicline, and cytisine produce discriminative stimulus effects through mecamylamine-sensitive receptors (i.e., nicotinic acetylcholine) in primates, whereas the involvement of DHßE-sensitive receptors (i.e., α4ß2) is unclear. The current nicotine-discrimination assay did not detect a difference in agonist efficacy between nicotine, varenicline, and cytisine, but did show evidence of involvement of dopamine. The control that nicotine has over choice behavior can be disrupted by non-nicotinic compounds, suggesting that non-nicotinics could be exploited to decrease the control that tobacco has over behavior.

The effects of nicotine, varenicline, and cytisine on schedule-controlled responding in mice: differences in α4ß2 nicotinic receptor activation.

Nicotine, varenicline, and cytisine are pharmacotherapies for tobacco dependence; the extent to which their in vivo effects vary as a function of differences in nicotinic acetylcholine receptor agonism is not clear. Male C57BL/6J mice responding under a fixed ratio 30 schedule of food delivery were used to establish the potency and time course of nicotine, varenicline, and cytisine; antagonism was examined with the non-competitive, non-selective antagonist mecamylamine and the competitive, α4ß2 nicotinic receptor antagonist dihydro-ß-erythroidine (DHßE). Intraperitoneal nicotine, varenicline, and cytisine dose-dependently decreased responding; nicotine was more potent (ED(50) value=0.83 mg/kg) than varenicline (ED(50) value=2.51 mg/kg) and cytisine (ED(50) value=2.97 mg/kg). The agonists had a similar time course including a rapid onset (5 min or less) and relatively short duration of action (30 min). Mecamylamine dose-dependently attenuated the rate-decreasing effects of a fixed dose of nicotine (1.78 mg/kg), varenicline (5.6 mg/kg), and cytisine (5.6 mg/kg). Mecamylamine (1mg/kg) produced parallel rightward shifts in the dose-response curves for nicotine (3.3-fold), varenicline (3.1-fold), and cytisine (2.3-fold). In contrast, DHßE (3.2mg/kg) produced 2-fold antagonism of nicotine and did not antagonize varenicline or cytisine. The data strongly suggest that nicotinic acetylcholine receptors mediate the effects of the agonists to decrease operant responding in mice. However, α4ß2 receptor agonism appears to contribute partially to the rate-decreasing effects of nicotine but not to the rate-decreasing effects of varenicline and cytisine. Differential activation of α4ß2 receptors in vivo might contribute to differences in the effectiveness of these smoking cessation aids.

When is a soil remediated? Comparison of biopiled and windrowed soils contaminated with bunker-fuel in a full-scale trial.

A six month field scale study was carried out to compare windrow turning and biopile techniques for the remediation of soil contaminated with bunker C fuel oil. End-point clean-up targets were defined by human risk assessment and ecotoxicological hazard assessment approaches. Replicate windrows and biopiles were amended with either nutrients and inocula, nutrients alone or no amendment. In addition to fractionated hydrocarbon analysis, culturable microbial characterisation and soil ecotoxicological assays were performed. This particular soil, heavy in texture and historically contaminated with bunker fuel was more effectively remediated by windrowing, but coarser textures may be more amendable to biopiling. This trial reveals the benefit of developing risk and hazard based approaches in defining end-point bioremediation of heavy hydrocarbons when engineered biopile or windrow are proposed as treatment option.