Global brands:The Evolution of Multinationals in Alcoholic Beverages. By Teresa da Silva Lopes. New York: Cambridge University Press, 2007. xxii + 303 pp. Illustrations, tables, appendix, bibliography, notes, index. Cloth, $50.00. ISBN: 978-0-521-83397-4.

Book review

Saccharomyces Cerevisiae as a biotechnological tool for ageing research:studies on translation and metabolism

The yeast Saccharomyces cerevisiae is an important model organism for the study of cell biology. The similarity between yeast and human genes and the conservation of fundamental pathways means it can be used to investigate characteristics of healthy and diseased cells throughout the lifespan. Yeast is an equally important biotechnological tool that has long been the organism of choice for the production of alcoholic beverages, bread and a large variety of industrial products. For example, yeast is used to manufacture biofuels, lubricants, detergents, industrial enzymes, food additives and pharmaceuticals such as anti-parasitics, anti-cancer compounds, hormones (including insulin), vaccines and nutraceuticals. Its function as a cell factory is possible because of the speed with which it can be grown to high cell yields, the knowledge that it is generally recognized as safe (GRAS) and the ease with which metabolism and cellular pathways, such as translation can be manipulated. In this thesis, these two pathways are explored in the context of their biotechnological application to ageing research: (i) understanding translational processes during the high-yielding production of membrane protein drug targets and (ii) the manipulation of yeast metabolism to study the molecule, L-carnosine, which has been proposed to have anti-ageing properties. In the first of these themes, the yeast strains, spt3?, srb5?, gcn5? and yTHCBMS1, were examined since they have been previously demonstrated to dramatically increase the yields of a target membrane protein (the aquaporin, Fps1) compared to wild-type cells. The mechanisms underlying this discovery were therefore investigated. All high yielding strains were shown to have an altered translational state (mostly characterised by an initiation block) and constitutive phosphorylation of the translational initiation factor, eIF2a. The relevance of the initiation block was further supported by the finding that other strains, with known initiation blocks, are also high yielding for Fps1. A correlation in all strains between increased Fps1 yields and increased production of the transcriptional activator protein, Gcn4, suggested that yields are subject to translational control. Analysis of the 5´ untranslated region (UTR) of FPS1 revealed two upstream open reading frames (uORFs). Mutagenesis data suggest that high yielding strains may circumvent these control elements through either a leaky scanning or a re-initiation mechanism. In the second theme, the dipeptide L-carnosine (ß-alanyl-L-histidine) was investigated: it has previously been shown to inhibit the growth of cancer cells but delay senescence in cultured human fibroblasts and extend the lifespan of male fruit flies. To understand these apparently contradictory properties, the effects of L-carnosine on yeast were studied. S. cerevisiae can respire aerobically when grown on a non-fermentable carbon source as a substrate but has a respiro-fermentative metabolism when grown on a fermentable carbon source; these metabolisms mimic normal cell and cancerous cell metabolisms, respectively. When yeast were grown on fermentable carbon sources, in the presence of L-carnosine, a reduction in cell growth and viability was observed, which was not apparent for cells grown on a non-fermentable carbon source. The metabolism-dependent mechanism was confirmed in the respiratory yeast species Pichia pastoris. Further analysis of S. cerevisiae yeast strains with deletions in their nutrient-sensing pathway, which result in an increase in respiratory metabolism, confirmed the metabolism-dependent effects of L-carnosine.

Using the theory of planned behaviour to understand binge drinking:the importance of beliefs for developing interventions

Objectives. To elicit students' salient beliefs in relation to binge drinking, and to examine the extent to which individual salient beliefs predict theory of planned behaviour (TPB) constructs in relation to binge drink, and actual drinking behaviour assessed later that evening. Design. Longitudinal, over a single evening. Methods. 192 students were recruited as they entered a campus bar at the beginning of the evening. They completed questionnaires with open-ended questions eliciting beliefs concerning binge drinking, and ratings scales assessing standard TPB constructs in relation to binge drinking. At the end of the evening, 181 completed a second questionnaire and recorded the number of alcoholic drinks they had consumed. Results. Beliefs were reliably coded (all kappas =0.79). Students with higher intentions to binge drink were more likely to believe that their friends approved of binge drinking, and that (lack of) money would make it difficult. Students who reported drinking more alcohol at the end of the evening were more likely to believe that getting drunk is an advantage/what they would like about binge drinking tonight, that their sports teams would approve, and that celebrating, drinking patterns, and environment would make it easy to binge drink. Conclusions. The present study has identified the individually salient beliefs relating to drinking behaviour that the TPB states should be addressed by interventions to alter behaviour, and which that should be assessed as mediators in intervention research. As a whole, these findings highlight the importance of perceived peer norms in binge drinking in this population, and support the idea of interventions to challenge the perception of social pressure to binge drink. ©2011 The British Psychological Society.

Azidoprofen as a soft anti-flammatory agent for the topical treatment of Psoriasis

Azidoprofen {2-(4-azidophenyl)propionic acid; AZP}, an azido-substituted arylalkanoic acid, was investigated as a model soft drug candidate for a potential topical non-steroidal anti-inflammatory agent (NSAIA). Reversed-phase high performance liquid chromatography (HPLC) methods were developed for the assay of AZP, a series of ester analogues and their· degradation products. 1H-NMR spectroscopy was also employed as an analytical method in selected cases. Reduction of the azido-group to the corresponding amine has been proposed as a potential detoxification mechanism for compounds bearing this substituent. An in vitro assay to measure the susceptibility of azides towards reduction was developed using dithiothreitol as a model reducing agent. The rate of reduction of AZP was found to be base-dependent, hence supporting the postulated mechanism of thiol-mediated reduction via nucleophilic attack by the thiolate anion. Prodrugs may enhance topical bioavailability through the manipulation of physico-chemical properties of the parent drug. A series of ester derivatives of AZP were investigated for their susceptibility to chemical and enzymatic hydrolysis, which regenerates the parent acid. Use of alcoholic cosolvents with differing alkyl functions to that of the ester resulted in transesterification reactions, which were found to be enzyme-mediated. The skin penetration of AZP was assessed using an in vitro hairless mouse skin model, and silastic membrane in some cases. The rate of permeation of AZP was found to be a similar magnitude to that of the well established NSAIA ibuprofen. Penetration rates were dependent on the vehicle pH and drug concentration when solutions were employed. In contrast, flux was independent of pH when suspension formulations were used. Pretreatment of the skin with various enhancer regimes, including oleic acid and azone in propylene glycol, promoted the penetration of AZP. An intense IR absorption due to the azide group serves as a highly diagnostic marker, enabling azido compounds to be detected in the outer layers of the· stratum corneum following their application to skin, using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). This novel application enabled a non-invasive examination of the percutaneous penetration enhancement of a model azido compound in vivo in man, in the presence of the enhancer oleic acid.

Under the influence? The construction of foetal alcohol syndrome in UK newspapers

Today, alongside many other proscriptions, women are expected to abstain or at least limit their alcohol consumption during pregnancy. This advice is reinforced through warning labels on bottles and cans of alcoholic drinks. In most (but not all) official policies, this is linked to a risk of Foetal Alcohol Syndrome (FAS) or one of its associated conditions. However, given that there is little medical evidence that low levels of alcohol consumption have an adverse impact on the foetus, we need to examine broader societal ideas to explain why this has now become a policy concern. This paper presents a quantitative and qualitative assessment of analysis of the media in this context. By analysing the frames over time, this paper will trace the emergence of concerns about alcohol consumption during pregnancy. It will argue that contemporary concerns about FAS are framed around a number of pre-existing discourses including alcohol consumption as a social problem, heightened concerns about children at risk and shifts in ideas about the responsibility of motherhood including during the pre-conception and pregnancy periods. Whilst the newspapers regularly carried critiques of the abstinence position now advocated, these challenges focused did little to refute current parenting cultures.

Changes in heart rate variability associated with moderate alcohol consumption

Technological advances have driven some attempt of vital parameters monitoring in adverse environments; these improvements will make possible to monitor cardiac activity also in automotive environments. In this scenario, heart rate changes associated with alcohol consumption, become of great importance to assess the drivers state during time. This paper presents the results of a first set of experiments aimed to discover heart rate variability modification induced by moderate assumption of alcoholic drink (i.e. single draft beer) as that typically occurs in weekend among some people. In the study, twenty subjects were enrolled and for each of them two electrocardiographic recordings were carried out: the first before alcohol ingestion and the second after 25-30 minutes. Each participant remained fasting until the second ECG acquisition was completed. ECG signal were analyzed by typical timedomain, frequency and non linear analysis. Results showed a small increase in LF/HF ratio which reflects a dominance of the sympathetic system over the parasympathetic system, and an increase in signal complexity as proven by non linear analysis. However, the study highlighted the need to monitor HRV starting from alcohol ingestion until its complete metabolization to allow a more precise description of its variation. © Springer International Publishing Switzerland 2014.