[en] A technique is presented for study of steady state kinetics of methadone using pulse labeling with deuterated methadone (d₃) and mass fragmentography to measure both unlabeled and labeled methadone in blood. Seven subjects maintained on methadone for at least 10 months were admitted to a closed metabolic ward. The daily dose of unlabeled methadone (d₀) was substituted by one dose of methadone-d₃ and plasma levels of methadone-d₀ and methadone-d₃ were followed for 48 h using a precise (SD +- 5%) and sensitive (30 pmol/ml) mass fragmentographic technique. Plasma half-lives (tsub(1/2)) for both methadone-d₀ and methadone-d₃ were calculated from samples obtained 8-24 h following the dose of methadone-d₃. The tsub(1/2) of oral methadone-d₃ was shorter (22 +- 2 h) than that of methadone-d₀ (52 +- 20 h). The same pattern was observed after intravenous administration. The results indicate multiple pools of methadone in the body. (orig.) 891 AJ/orig. 892 MKO

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[en] Highlights: • Resistant E. coli competing with susceptible one changed with DOX concentrations. • Low proportion of resistant E. coli coexisted with susceptible E. coli without DOX. • Fitness cost of resistant E. coli reduced during sublethal challenge of DOX. • Metabonomics reveals different metabolisms in the resistant and susceptible E. coli. • Pyruvate and pilocarpine were biomarkers of alleviation of fitness cost. High concentrations of antibiotics may induce bacterial resistance mutations and further lead to fitness costs by reducing growth of resistant bacteria. However, antibiotic concentrations faced by bacteria are usually low in common environments, which leads to questions about how resistant bacteria with fitness costs regulate metabolism to coexist or compete with susceptible bacteria during sublethal challenge. Our study revealed that a low proportion (< 15%) of resistant bacteria coexisted with susceptible bacteria due to the fitness cost without doxycycline. However, the cost for the resistant strain decreased at a doxycycline concentration of 1 mg/L and even disappeared when the doxycycline concentration was 2 mg/L. Metabonomics analysis revealed that bypass carbon metabolism and biosynthesis of secondary metabolites were the primary metabolic pathways enriching various upregulated metabolites in resistant bacteria without doxycycline. Moreover, the alleviation of fitness cost for resistant bacteria competed with susceptible bacteria at 1 mg/L doxycycline was correlated with the downregulation of the biomarkers pyruvate and pilocarpine. Our study offered new insight into the metabolic mechanisms by which the fitness cost of resistant mutants was reduced at doxycycline concentrations as low as 1 mg/L and identified various potential metabolites to limit the spread of antimicrobial resistance in the environment.

[en] A set of reactivity indices, including maps of the electrostatic potential and local and condensed Fukui function (FF) indices in the atomic resolution, are reported for two vasoconstricting mycotoxins: butenolide and ergotamine; both the finite difference approach of Parr and Yan as well as charge sensitivity analysis, determining the charge responses via the inversion of the hardness tensor, have been used to generate the FF data. These two routes of arriving at the atomic FF indices provide an opportunity to evaluate the available parametrizations of the semiempirical NDDO-type of methods which have been used to determine the input charge distribution; namely, the best parametrization should generate consistent FF predictions resulting from both approaches. For butenolide, the MNDO parametrization was found to fulfill this consistency requirement. The chemical reactivity information has been used to trace possible similarities in reactivity trends of the butenolide molecule and the related fragment of ergotamine, toward hypothetical nucleophilic, electrophilic, and radical attacks. These predictions have been compared to experimental data available for other unsaturated lactones. 13 refs., 18 figs., 1 tab

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[en] A study of the effects of dehydration, atropine, terbutaline and N-acetylcysteine on canine tracheobronchial mucus is presented. Mucociliary clearance rates, mucus secretion volumes and mucus rheologic properties were studied. Clearance rates were studied by a radioisotope technique mucus collected by a canine Tracheal pouch method and rheologic studies performed on a microrheometer. Clearance rate was unaffected by dehydration and terbutaline, increased by N-acetylcysteine and decreased by atropine. Secretion volume was increased by terbutaline while dehydration and atropine were without effect. Rheologic factors were increased by dehydration and atropine while terbutaline was without an effect. The effects of N-acetylcysteine on secretion volume and rheologic properties could not be studied because of the nature of the techniques employed

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[en] Colchicine-induced autotetraploids of three Achimenes cultivars were irradiated with X-rays or fast neutrons. The results were compared, in one cultivar, with those of the irradiated diploid form. The mutation frequency after irradiation of the autotetraploid was a 20-40 fold higher as compared to the corresponding diploid. These results may open new possibilities for mutation breeding, though they are hard to explain. Several promising mutants were selected. (author)

No abstract available