The effect of acute alcohol exposure on hepatic oxidative stress and function: prevention by micronutrients

Alcohol binge drinking, especially in teenagers and young adults is a major public health issue in the UK, with the number of alcohol related liver disorders steadily increasing. Understanding the mechanisms behind liver disease arising from binge-drinking and finding ways to prevent such damage are currently important areas of research. In the present investigation the effect of acute ethanol administration on hepatic oxidative damage and apoptosis was examined using both an in vivo and in vitro approach; the effect of micronutrient supplementation prior and during ethanol exposure was also studied. The following studies were performed: (1) ethanol administration (75 mmol/kg body weight) and cyanamide pre-treatment followed by ethanol to study elevated acetaldehyde levels with liver tissue analysed 2.5, 6 and 24 hours post-alcohol; (2). Using juvenile animals, 2% betaine supplementation followed by acute ethanol with tissue analysed 24 hrs post ethanol; and (3). Micronutrient supplementation during concomitant ethanol exposure to hepG2 cells. It was found that a single dose of alcohol caused oxidative damage to the liver of rats at 2.5 hr post-alcohol as evidenced by decreased glutathione levels and increased malondialdehyde levels in both the cytosol and mitochondria. Liver function was also depressed but there were no findings of apoptosis as cytochrome c levels and caspase 3 activity was unchanged. At 6 hours, the effect of ethanol was reduced suggesting some degree of recovery, however, by 24 hours, increased mitochondrial oxidative stress was apparent. The effect of elevated acetaldehyde on hepatic damage was particularly evident at 24 hours, with some oxidative changes at earlier time points. At 24 hours, acetaldehyde caused a profound drop in glutathione levels in the cytosol and hepatic function was still deteriorating. Studies examining ethanol exposure to juvenile livers showed that glutathione levels were increased, suggesting an overtly protective response not seen in with older animals. It also showed that despite cytochrome c release into the cytosol, caspase-3 levels were not increased. This suggests that ATP depletion is preventing apoptosis initiation. Betaine supplementation prevented almost all of the alcohol-mediated changes, suggesting that the main mechanism behind alcohol-mediated liver damage is oxidative stress. Results using the hepG2 cell line model showed that micronutrients involved in glutathione synthesis can protect against hepatocyte damage caused by alcohol metabolism, with reduced reactive oxygen species and increased/maintained glutathione levels. In summary, these results demonstrate that both acute alcohol and acetaldehyde can have damaging effects to the liver, but that dietary intervention may be able to protect against ethanol induced oxidative stress.

Labour and the politics of alcohol: the decline of a cause

This paper shows that, contrary to existing historiography, the politics of alcohol remained important within the Labour party. It explains how and why the party thereafter moved away from this issue and the consequences in terms of party policy up to the 2003 Licensing Act.

Best practice factory for freight transport in Europe: demonstrating how ‘good’ urban freight cases are improving business profit and public sectors benefits

The objective of this study is to better understand why selected urban freight solutions represent innovations that are technically feasible, economically profitable in different contexts, sustainable, transferable, and with tangible beneficial impacts. A total of 15 solutions are evaluated in the fields of Urban Consolidation Centre, clean and electric vehicles, IT solutions, use of urban waterways, and others. Three solutions are analysed more thoroughly, the Cityporto Padova, the Basel Exhibition Centre logistics support system, and the Berlin laboratory area test of the Bentobox. This paper ends with a transversal analysis of the solutions observed, and with methodological conclusions.

Best practice factory for freight transport in Europe: demonstrating how ‘good’ urban freight cases are improving business profit and public sectors benefits

The objective of this study is to better understand why selected urban freight solutions represent innovations that are technically feasible, economically profitable in different contexts, sustainable, transferable, and with tangible beneficial impacts. A total of 15 solutions are evaluated in the fields of Urban Consolidation Centre, clean and electric vehicles, IT solutions, use of urban waterways, and others. Three solutions are analysed more thoroughly, the Cityporto Padova, the Basel Exhibition Centre logistics support system, and the Berlin laboratory area test of the Bentobox. This paper ends with a transversal analysis of the solutions observed, and with methodological conclusions.