Cytochromes P450 (CYPs) metabolize a vast array of xenobiotics, including many drugs and toxins. Induction or downregulation of the CYPs can have important consequences such as changes in drug efficacy and altered susceptibility to toxicity. Our study investigated the independent and combined effects of ethanol and nicotine on hepatic and/or brain levels of CYP2E1, CYP2B6 and CYP2A6 in African green monkeys. Monkeys were randomized into four groups (N = 10/group): an ethanol-only group, a nicotine-only group, an ethanol + nicotine group and a control (no drug) group. Ethanol (10% ethanol in sucrose solution) was voluntarily self-administered by the monkeys and nicotine was given as subcutaneous injections (0.5 mg/kg bid). Protein levels and/or in vitro activity were assessed in liver and brain tissue. Also, in vivo pharmacokinetics for chlorzoxazone (metabolized selectively by CYP2E1) and nicotine (metabolized primarily by CYP2A6 and to a lesser extent CYP2B6) were assessed. Hepatic CYP2E1 protein levels, in vitro hepatic CYP2E1 activity and in vivo chlorzoxazone metabolism were increased by ethanol and nicotine, alone and in combination. Hepatic CYP2B6 protein levels and in vitro hepatic CYP2B6 activity were increased by ethanol alone or combined ethanol and nicotine exposure, but were unaffected by nicotine alone. Hepatic CYP2A6 protein levels and in vitro hepatic CYP2A6 activity were decreased by nicotine alone or combined ethanol and nicotine exposure, but unaffected by ethanol alone. Chronic nicotine resulted in higher nicotine plasma levels achieved after nicotine administration, consistent with decreased CYP2A6 activity. Ethanol, alone or combined with nicotine, resulted in lower nicotine plasma levels, an effect that was not mediated by changes in CYP activity. Protein levels of CYP2E1 and CYP2B6 were induced in specific regions and cells in the brain as a result of ethanol self-administration, nicotine treatment and the combined exposure to both drugs. In summary, ethanol and nicotine can alter the expression and/or activity of several important CYP2 family enzymes in primate liver and/or brain.

Maternal ethanol consumption during pregnancy can produce teratogenic outcomes in offspring, which are collectively termed Fetal Alcohol Spectrum Disorder (FASD). Central nervous system (CNS) dysfunction is a debilitating and permanent manifestation of FASD. Recent studies indicate that chronic prenatal ethanol exposure (CPEE), via maternal ethanol administration, also impairs metabolic function in offspring. The mechanism of ethanol teratogenicity is multi-faceted and could involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also involved in CNS neuronal survival and plasticity, which are impaired by CPEE. The overall goal of this thesis research was to study, in the guinea pig, neurobehavioural and metabolic effects of CPEE and to investigate whether these effects were associated with altered CNS and peripheral insulin/IGF signaling pathways. In postnatal offspring, CPEE decreased brain weight and altered performance of the modified Biel-maze task, which was a sensitive measure of apparent cognitive dysfunction and executive function deficits. Furthermore, CPEE produced various manifestations of metabolic teratogenicity in offspring, including decreased birth weight, postnatal catch-up body growth, increased whole-body adiposity, disrupted pancreatic morphology, dysregulation of blood glucose concentration and increased liver weight in adulthood. The CPEE-induced neurobehavioural and metabolic effects were associated with alterations of the insulin/IGF signaling pathways in the CNS and periphery. In the liver, CPEE decreased mRNA expression of IGF-1, IGF-1 receptor, and IGF-2 in male and female offspring, and increased mRNA expression of insulin receptor substrate (IRS)-2 in male offspring only compared with nutritional control. Female CPEE offspring had decreased hepatic mRNA expression of insulin receptor compared with male CPEE offspring. In the prefrontal cortex, IRS-2 mRNA expression was increased in male and female CPEE offspring compared with nutritional control. The studies of this thesis have contributed to the understanding of the neurobehavioural and metabolic consequences of CPEE in offspring, which are associated with impairment of the insulin/IGF signaling pathways. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2014-04-25 10:52:50.048

The objective was to create a feasibility framework for assessing the feasibility of a cellulosic ethanol refinery. In addition, the research aimed to create a base case scenario based on data from literature and conduct sensitivity analysis to determine significant parameters of a cellulosic ethanol refinery. The base case was found to be not feasible in the financial and economic analysis given the assumptions used.

No description available.

No description available.

In order to produce ethanol derived from lignocellulosic feeds at a cost that is competitive with current gasoline prices, the fermentation process, converting sugars to produce ethanol and the subsequent purification steps, must be enhanced. Due to their comparatively lower costs, the widespread availability across a range of climates, and their status as a dedicated energy crop, lignocellulosic biomass feeds are ideal raw materials that can be used to produce domestic fuels to partly displace our dependence on non-renewable sources. Currently, a major drawback of the technology is the relatively low ethanol tolerance of the micro-organisms used to ferment xylose and glucose. To alleviate the ethanol inhibition of Escherichia coli KO11 (ATCC 55124) during fermentation, online ethanol sequestration was achieved through the implementation of an externally located packed bed adsorber for the purpose of on-line ethanol removal (using F-600 activated carbon). By removing ethanol from the broth during the fermentation, inhibition due to the presence of ethanol could be alleviated, enhancing the substrate utilization and fermentation rate and the ethanol production of the fermentation. This study details a comprehensive adsorbent screening to identify ethanol selective materials, modelling of multi-component adsorption systems, and the design, implementation and modelling of a fermentation unit coupled with an externally located packed bed adsorber.

In New Zealand, it is common for young people to mix 1-benzylpiperazine (BZP) containing 'party pills' and ethanol (drinking alcohol). However, there is no scientific literature which compares the individual and combined long-term effects of these substances. Therefore, the aim of this study was to provide a comparison of BZP and ethanol's individual and combined effects on adulthood behaviour following repeated adolescent exposure. To investigate this 40 male and 40 female adolescent rats received daily exposure (post natal days 41 - 50) to BZP (10 mg/kg) and/or ethanol (2 g/kg) or saline vehicle (1 ml/kg) via intraperitoneal injection. Animals were tested in a Y maze, light/dark emergence box, and an open field during early adulthood (PND 78 - 81) and again during mid-adulthood (PND 117 - 120). Results found females treated with alcohol ambulated less in the open field. Interestingly, no other behavioural differences between the treatment groups were observed. Overall, it appeared that adolescent exposure to BZP and/or alcohol did not have long-term behavioural consequences, at least in rats. This finding was most likely due to the narrow range of testing ages adopted in the study.

Part of Thesis (Ph. D.)--University of Chicago, 1933. / Lithoprinted. "Private edition, distributed by the University of Chicago libraries, Chicago, Illinois."

Thesis (Ph. D.)--University of Virginia, 1999. / Spine title: Acyl chain asymmetry of PG. Includes bibliographical references (p. 166-182). Also available online through Digital Dissertations.

Hohenheim, Univ., Diss., 2001.