27 July 2018 In Dementia

BACKGROUND: Microglial activation contributes to the neuropathology associated with chronic alcohol exposure and withdrawal, including the expression of inflammatory and anti-inflammatory genes. In the current study, we examined the transcriptome of primary rat microglial cells following incubation with alcohol alone, or alcohol together with a robust inflammatory stimulus.

METHODS: Primary microglia were prepared from mixed rat glial cultures. Cells were incubated with 75 mM ethanol alone or with proinflammatory cytokines ("TII": IL1beta, IFNgamma, and TNFalpha). Isolated mRNA was used for RNAseq analysis and qPCR. Effects of alcohol on phagocytosis were determined by uptake of oligomeric amyloid beta.

RESULTS: Alcohol induced nitrite production in control cells and increased nitrite production in cells co-treated with TII. RNAseq analysis of microglia exposed for 24 h to alcohol identified 312 differentially expressed mRNAs ("Alc-DEs"), with changes confirmed by qPCR analysis. Gene ontology analysis identified phagosome as one of the highest-ranking KEGG pathways including transcripts regulating phagocytosis. Alcohol also increased several complement-related mRNAs that have roles in phagocytosis, including C1qa, b, and c; C3; and C3aR1. RNAseq analysis identified over 3000 differentially expressed mRNAs in microglia following overnight incubation with TII; and comparison to the group of Alc-DEs revealed 87 mRNAs modulated by alcohol but not by TII, including C1qa, b, and c. Consistent with observed changes in phagocytosis-related mRNAs, the uptake of amyloid beta1-42, by primary microglia, was reduced by alcohol.

CONCLUSIONS: Our results define alterations that occur to microglial gene expression following alcohol exposure and suggest that alcohol effects on phagocytosis could contribute to the development of Alzheimer's disease.

27 July 2018 In Cardiovascular System

Moderate alcohol consumption has been associated with a lower risk of coronary artery disease (CAD) in the general population but has not been well studied in US veterans. We obtained self-reported alcohol consumption from Million Veteran Program participants. Using electronic health records, CAD events were defined as 1 inpatient or 2 outpatient diagnosis codes for CAD, or 1 code for a coronary procedure. We excluded participants with prevalent CAD (n = 69,995) or incomplete alcohol information (n = 8,449). We used a Cox proportional hazards model to estimate hazard ratios and 95% confidence intervals for CAD, adjusting for age, gender, body mass index, race, smoking, education, and exercise. Among 156,728 participants, the mean age was 65.3 years (standard deviation = 12.1) and 91% were men. There were 6,153 CAD events during a mean follow-up of 2.9 years. Adjusted hazard ratios (95% confidence intervals) for CAD were 1.00 (reference), 1.02 (0.92 to 1.13), 0.83 (0.74 to 0.93), 0.77 (0.67 to 0.87), 0.71 (0.62 to 0.81), 0.62 (0.51 to 0.76), 0.58 (0.46 to 0.74), and 0.95 (0.85 to 1.06) for categories of never drinker; former drinker; current drinkers of 0.5 to 1 drink/day, >1 to 2 drinks/day, >2 to 3 drinks/day, and >3 to 4 drinks/day; and heavy drinkers (>4 drinks/day) or alcohol use disorder, respectively. For a fixed amount of ethanol, intake at >/=3 days/week was associated with lower CAD risk compared with </=1 day/week. Beverage preference (beer, wine, or liquor) did not influence the alcohol-CAD relation. Our data show a lower risk of CAD with light-to-moderate alcohol consumption among US veterans, and drinking frequency may provide a further reduction in risk.

27 July 2018 In Cardiovascular System

BACKGROUND: Although it is well established that heavy alcohol consumption increases the risk of hypertension, the risk associated with low levels of alcohol intake in men and women is unclear.

METHODS AND RESULTS: We searched Medline and Embase for original cohort studies on the association between average alcohol consumption and incidence of hypertension in people without hypertension. Random-effects meta-analyses and metaregressions were conducted. Data from 20 articles with 361 254 participants (125 907 men and 235 347 women) and 90 160 incident cases of hypertension (32 426 men and 57 734 women) were included. In people drinking 1 to 2 drinks/day (12 g of pure ethanol per drink), incidence of hypertension differed between men and women (relative riskwomen vs men=0.79; 95% confidence interval, 0.67-0.93). In men, the risk for hypertension in comparison with abstainers was relative risk=1.19 (1.07-1.31; I(2)=59%), 1.51 (1.30-1.76), and 1.74 (1.35-2.24) for consumption of 1 to 2, 3 to 4, and 5 or more standard drinks per day, respectively. In women, there was no increased risk for 1 to 2 drinks/day (relative risk=0.94; 0.88-1.01; I(2)=73%), and an increased risk for consumption beyond this level (relative risk=1.42; 1.22-1.66).

CONCLUSIONS: Any alcohol consumption was associated with an increase in the risk for hypertension in men. In women, there was no risk increase for consumption of 1 to 2 drinks/day and an increased risk for higher consumption levels. We did not find evidence for a protective effect of alcohol consumption in women, contrary to earlier meta-analyses.

18 May 2018 In General Health

The introduction of the term "French Paradox" motivated an extensive and in-depth research into health benefits of moderate wine consumption. The superiority of wine is thought to be attributed to its micro-constituents and consequent effort was made to isolate and identify these bioactive compounds as well as to elucidate the mechanisms of their action. Controlled trials offer more concrete answers to several raised questions than observational studies. Under this perspective, clinical trials have been implemented, mainly in healthy volunteers and rarely in patients, in order to investigate the acute or chronic effect of wine consumption on metabolism and physio-pathological systems, which are mainly associated with cardiovascular diseases. The aim of this review is to update the knowledge about the acute and long term effect of wine consumption on lipid and glucose/insulin metabolism as well as on the inflammatory and haemostatic systems, based on the reported data of controlled clinical trials. In conclusion, the most repeated result of wine consumption is on lipid metabolism, attributed mainly to ethanol, while wine micro-constituents seem to have an important role mainly in haemostatic and inflammatory/endothelial systems.

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