Browsing by Author "Liu, Xin"

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    In vitro and in vivo studies on the biotransformation of β-nicotyrine, a minor tobacco alkaloid
    Liu, Xin (Virginia Tech, 1995-06-05)
    β-Nicotyrine is a minor tobacco alkaloid found in both tobacco plants and tobacco smoke. Preliminary studies have shown that β-nicotyrine is pneumotoxic and that the toxicity is mediated via its metabolites formed in reactions catalyzed by cytochrome P-450. The in vitro metabolic fate of β-nicotyrine has been examined in rat liver microsomal preparations and rabbit lung and liver microsomal preparations utilizing HPLC UV-diode array analysis. Four metabolites have been identified from the incubation mixtures of β-nicotyrine with rabbit lung and liver microsomal preparations. The primary in vitro metabolites are two unstable pyrrolinone species, 1-methyl-5-(3-pyridyl)-4-pyrrolin-2-one and 1-methyl-5-(3-pyridyl)-3-pyrrolin-2-one, which exist in equilibrium. The pyrrolinones undergo autoxidation to form a secondary metabolite, 5-hydroxy-1-methyl-S-(3-pyridyl)-3-pyrrolin-2-one, and hydrolysis to form 5'-hydroxycotinine. The autoxidation is likely to involve a free radical process. Evidence to support this proposal has been obtained by studies on 2-acetoxy-1-methyl-5-(3-pyridyl)pyrrole, a latent form of the pyrrolinones. Free radicals generated following hydrolysis of the acetoxypyrrole derivative have been trapped and detected by ESR analysis by spin trapping techniques. In contrast, only the starting substrate β-nicotyrine was found in the incubation mixture of β-nicotyrine with rat liver microsomes. The in vivo metabolic fate of β-nicotyrine has been examined in rabbits and mice by HPLC UV-diode array and GC-EIMS analysis of urine extracts. Three metabolites have been identified. Besides S'-hydroxycotinine and 5-hydroxy-1-methyl-5-(3-pyridyl)-3-pyrrolin-2-one, observed in the in vitro studies, 3'-hydroxycotinine is also found and determined to be the principal urinary metabolite of β-nicotyrine in both species. The stereochemistry of this 3'-hydroxycotinine is cis. This is in contrast to the trans stereochemistry of the urinary metabolite of (S)-cotinine and (S)-nicotine. The mechanism of formation of cis-3'-hydroxycotinine from β-nicotyrine is proposed to involve a free radical process leading to the formation of the precursor 3-hydroxy-1-methyl-5-(3- pyridyl)-4-pyrrolin-2-one. This intermediate then undergoes a carbon-carbon double bond reduction to yield the final product. This proposal is supported by in vivo studies on 5-hydroxy-1-methyl-5-(3-pyridyl)-3-pyrrolin-2-one which undergoes reduction to 5'-hydroxycotinine. Furthermore, 2-acetoxy-1-methyl-5- (3-pyridyl)pyrrole goes to cis-3'-hydroxycotinine as the major urinary metabolite. The results of these studies point to a potentially novel metabolic bioactivation pathway of (S)-nicotine that could be relevant to some of the toxic effects observed in chronic tobacco users.
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    Packing Characteristics of Aggregate with Consideration of Particle size and Morphology
    Miao, Yinghao; Liu, Xin; Hou, Yue; Li, Juan; Wu, Jiaqi; Wang, Linbing (MDPI, 2019-02-28)
    The packing characteristics of aggregates are very important for aggregate blend design, which is closely related to the performance of mixtures. In this study, an indoor packing experiment was designed to investigate the behaviors of single-size particle packing and two-size particle packing. The effects of particle composition, particle size and size ratio, particle morphology on packing characteristics were also evaluated. Two kinds of aggregates (crushed stone and gravel) with significant morphological differences were selected for the test. The angularity of the aggregates was quantitatively analyzed using the variance of mean curvature ( S C m 2 ) of particle surface in accordance with the 3-D scanning measurements. Based on the test results, the packing characteristics of aggregates were analyzed using the air void content (Va) and the packing function index (Ipf) proposed in this paper. It is shown that the analysis results of packed ideal spheres cannot be directly used to describe the packing characteristics of aggregates. Particle morphology has a significant impact on packing characteristics, especially on the Va. The Va of packed aggregates with poor angularity is significantly smaller than that with good angularity. Ipf can be used to quantitatively distinguish the packing function of particles. The test results show that the packing function of particles cannot be simply divided into the skeleton building and air voids filling. Generally, the particles in packed blend have both of these functions. The packing function of particles depends not only on the particle size, but also on the composition of particles with different size. When the size ratio and volume ratio are the same, the packing characteristics of the two-size particle blends will still change with the change of the particle size. The exploration of packing behaviors of single- size and two- size particle aggregates is helpful for analyzing the packing behaviors of blends with multi-size particles.