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.

Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment

The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise significant risk factors. Here, we aimed to advance our hypothesis that glucocorticoids (GCs), recognised key players in neurobiological programming, target development within these systems, with a novel focus on the astrocytic population. Mice received antenatal GC treatment (AGT) by including the synthetic GC, dexamethasone, in the mothers' drinking water on gestational days 16-19; controls received normal drinking water. Analyses of regional shapes and volumes of the adult SNc and VTA demonstrated that AGT induced long-term, dose-dependent, structural changes that were accompanied by profound effects on astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT induced long-term changes in the population size and distribution of SNc/VTA dopaminergic neurons, confirming and extending our previous observations made in rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within the neonatal brain revealed that these long-term organisational effects of AGT depend, at least in part, on targeting perinatal processes that determine astrocyte density and programmed cell death in dopaminergic neurons. Collectively, our characterisation of enduring, AGT-induced, sex-specific cytoarchitectural disturbances suggests novel mechanistic links for the strong association between early environmental challenge (inappropriate exposure to excess GCs) and vulnerability to developing aberrant behaviours in later life, with translational implications for dopamine-associated disorders (such as schizophrenia, ADHD, autism, depression), which typically show a sex bias

Habitual coffee and tea drinkers experienced increases in blood pressure after consuming low to moderate doses of caffeine; these increases were larger upright than in the supine posture

Caffeine users have been encouraged to consume caffeine regularly to maintain their caffeine tolerance and so avoid caffeine’s acute pressor effects. In controlled conditions complete caffeine tolerance to intervention doses of 250 mg develops rapidly following several days of caffeine ingestion, nevertheless, complete tolerance is not evident for lower intervention doses. Similarly complete caffeine tolerance to 250 mg intervention doses has been demonstrated in habitual coffee and tea drinkers’ but for lower intervention doses complete tolerance is not evident. This study investigated a group of habitual caffeine users following their self-determined consumption pattern involving two to six servings daily. Cardiovascular responses following the ingestion of low to moderate amounts caffeine (67, 133 and 200 mg) were compared with placebo in a double-blind, randomised design without caffeine abstinence. Pre-intervention and post-intervention (30 and 60 min) 90 s continuous cardiovascular recordings were obtained with the Finometer in both the supine and upright postures. Participants were 12 healthy habitual coffee and tea drinkers (10 female, mean age 36). Doses of 67 and 133 mg increased systolic pressure in both postures while in the upright posture diastolic pressure and aortic impedance increased while arterial compliance decreased. These vascular changes were larger upright than supine for 133 mg caffeine. Additionally 67 mg caffeine increased dp/dt and indexed peripheral resistance in the upright posture. For 200 mg caffeine there was complete caffeine tolerance. Cardiovascular responses to caffeine appear to be associated with the size of the intervention dose. Habitual tea and coffee drinking does not generate complete tolerance to caffeine as has been previously suggested. Both the type and the extent of caffeine induced cardiovascular changes were influenced by posture.

The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity

The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity. Introduction: Caffeine is detected by 5 of the 25 gustatory bitter taste receptors (hTAS2Rs) as well as by intestinal STC-1 cell lines. Thus there is a possibility that caffeine may elicit reflex autonomic responses via chemosensory stimulation. Methods: The cardiovascular impacts of double-espresso coffee, regular (130 mg caffeine) and decaffeinated, and encapsulated caffeine (134 mg) were compared with a placebocontrol capsule. Measures of four post-ingestion phases were extracted from a continuous recording of cardiovascular parameters and contrasted with pre-ingestion measures. Participants (12 women) were seated in all but the last phase when they were standing. Results: Both coffees increased heart rate immediately after ingestion by decreasing both the diastolic interval and ejection time. The increases in heart rate following the ingestion of regular coffee extended for 30 min. Encapsulated caffeine decreased arterial compliance and increased diastolic pressure when present in the gut and later in the standing posture. Discussion: These divergent findings indicate that during ingestion the caffeine in coffee can elicit autonomic arousal via the chemosensory stimulation of the gustatory receptors which extends for at least 30 min. In contrast, encapsulated caffeine can stimulate gastrointestinal receptors and elicit vascular responses involving digestion. Conclusion: Research findings on caffeine are not directly applicable to coffee and vice versa. The increase of heart rate resulting from coffee drinking is a plausible pharmacological explanation for the observation that coffee increases risk for coronary heart disease in the hour after ingestion.

Drink availability is associated with enhanced examination performance in adults

While dehydration has negative effects on memory and attention, few studies have investigated whether drinking water can enhance cognitive performance, and none have addressed this in a real-world setting. In this study we explored the potential benefits of the availability of water for undergraduates. The exam performance of students who brought drinks in to exams was compared with those that did not for three cohorts of undergraduates (N = 447). We employed earlier coursework marks as a measure of underlying ability. Students who brought water to the exam achieved better grades than students who did not. When coursework marks were covaried, this effect remained statistically significant, suggesting that this finding was not simply due to more able students being more likely to bring in water. This implies that water consumption may facilitate performance in real-world settings, and, therefore, have specific implications for the assessment of undergraduate learners under examination conditions, but further research is required to evaluate this hypothesis.

A randomized trial to assess the potential of different beverages to affect hydration status: development of a beverage hydration index

Background: The identification of beverages that promote longer- term fluid retention and maintenance of fluid balance is of real clinical and practical benefit in situations in which free access to fluids is limited or when frequent breaks for urination are not desirable. The postingestion diuretic response is likely to be influenced by several beverage characteristics, including the volume ingested, energy den- sity, electrolyte content, and the presence of diuretic agents. Objective: This study investigated the effects of 13 different com- monly consumed drinks on urine output and fluid balance when ingested in a euhydrated state, with a view to establishing a beverage hydration index (BHI), i.e., the volume of urine produced after drinking expressed relative to a standard treatment (still water) for each beverage. Design: Each subject (n = 72, euhydrated and fasted male subjects) ingested 1 L still water or 1 of 3 other commercially available beverages over a period of 30 min. Urine output was then collected for the subsequent 4 h. The BHI was corrected for the water content of drinks and was calculated as the amount of water retained at 2 h after ingestion relative to that observed after the ingestion of still water. Results: Total urine masses (mean 6 SD) over 4 h were smaller than the still-water control (1337 6 330 g) after an oral rehydration solution (ORS) (1038 6 333 g, P , 0.001), full-fat milk (1052 6 267 g, P , 0.001), and skimmed milk (1049 6 334 g, P , 0.001). Cumulative urine output at 4 h after ingestion of cola, diet cola, hot tea, iced tea, coffee, lager, orange juice, sparkling water, and a sports drink were not different from the response to water ingestion. The mean BHI at 2 h was 1.54 6 0.74 for the ORS, 1.50 6 0.58 for full- fat milk, and 1.58 6 0.60 for skimmed milk. Conclusions: BHI may be a useful measure to identify the short- term hydration potential of different beverages when ingested in a euhydrated state.

Understanding the Effect of Television Advertising on Women's Attitudes and Purchase Intentions Towards Beer: A Study of Three Major Brands.

Abstract Purpose of Paper: The market for beer in the UK is now mature and sales have been stable at around £16bn for about ten years (Mintel 2014). More recently, there have been changes in the market as consumers have switched from bigger mainstream brands to a growing number of smaller craft beers. However, in order to grow further significantly, the industry needs to explore new market segments and find new consumers for beer. So far, it is estimated that only 1.3m women in the UK drink beer (O'Reilly, 2014; Mail Online, 2015). Women are therefore an underexplored segment and present the main growth opportunity for beer drinking in the UK. However, most beer television advertising has traditionally been aimed at the male audience and there have been suggestions that some of this advertising has been seen as unpopular with or even insulting to women (Jackson, 2013; Zwarun et al., 2006). The Chief Executive of major brewer SAB Miller, which owns the Foster's brand, has recently written that, 'We have to acknowledge that core lager advertising, for many years, was either dismissive of, or insulting to, women.' (Shubber, 2015). If women are to be the new consumers and the future target for beer advertising, there is therefore a significant gap in the knowledge and literature concerned with how women differ from men in responding to the television advertising produced by beer brands and it is important that this gap in knowledge is addressed. The purpose of this paper is therefore to explore the effect of the television advertising of the three top selling UK beer brands on women's attitudes and purchase intentions towards those brands. More specifically, the objectives are: 1) To gain an understanding of how female consumers respond to existing beer television advertising, specifically in terms of the ‘likeability’ of the content of TV commercials produced by the three leading UK beer brands among female consumers. 2) To examine the effect of the rational and emotional content, including the use of humour, in television commercials produced by the three leading UK beer brands on the attitudes of female consumers towards those brands. 3) To explore in-depth female consumer attitudes towards the content (message cues and symbolism) of the television commercials produced by the three leading beer brands in the UK and their effect on subsequent purchase intentions for each brand.