Moderate alcohol consumption after a mental stressor attenuates the endocrine stress response.

Alcohol is often consumed to reduce tension and improve mood when exposed to stressful situations. Previous studies showed that moderate alcohol consumption may reduce stress when alcohol is consumed prior to a stressor, but data on the effect of alcohol consumption after a mental stressor is limited. Therefore, our objective was to study whether moderate alcohol consumption immediately after a mental stressor attenuates the stress response. Twenty-four healthy men (age 21-40 y, BMI 18-27 kg/m2) participated in a placebo-controlled trial. They randomly consumed 2 cans (660 mL, ∼26 g alcohol) of beer or alcohol-free beer immediately after a mental stressor (Stroop task and Trier Social Stress Test). Physiological and immunological stress response was measured by monitoring heart rate and repeated measures of the hypothalamic-pituitary-adrenal axis (HPA-axis), white blood cells and a set of cytokines. After a mental stressor, cortisol and adrenocorticotropic hormone (ACTH) concentrations were 100% and 176% more reduced at 60 min (P = 0.012 and P = 0.001, respectively) and 92% and 60% more reduced at 90 min (P < 0.001 and P = 0.056, respectively) after beer consumption as compared to alcohol-free beer consumption. Heart rate and dehydroepiandrosterone (DHEA) were not influenced by alcohol consumption. Plasma IL-8 concentrations remained lower during the stress recovery period after beer consumption than after alcohol-free beer consumption (P < 0.001). In conclusion, consumption of a moderate dose of alcohol after a mental stressor may facilitate recovery of the endocrine stress response as reflected by decreasing plasma ACTH and cortisol.

Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1.

Moderate alcohol consumption increases HDL cholesterol, which is involved in reverse cholesterol transport (RCT). The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux, using J774 mouse macrophages and Fu5AH cells, and on other parameters in the RCT pathway. Twenty-three healthy men (45-65 years) participated in a randomized, partially diet-controlled, crossover trial. They consumed four glasses of whisky (40 g of alcohol) or water daily for 17 days. After 17 days of whisky consumption, serum capacity to induce ABCA1-dependent cholesterol efflux from J774 mouse macrophages was increased by 17.5% (P = 0.027) compared with water consumption. Plasma capacity to induce cholesterol efflux from Fu5AH cells increased by 4.6% (P = 0.002). Prebeta-HDL, apolipoprotein A-I (apoA-I), and lipoprotein A-I:A-II also increased by 31.6, 6.2, and 5.7% (P < 0.05), respectively, after whisky consumption compared with water consumption. Changes of cAMP-stimulated cholesterol efflux correlated (r = 0.65, P < 0.05) with changes of apoA-I but not with changes of prebeta-HDL (r = 0.30, P = 0.18). Cholesterol efflux capacities from serum of lean men were higher than those from overweight men. In conclusion, this study shows that moderate alcohol consumption increases the capacity of serum to induce cholesterol efflux from J774 mouse macrophages, which may be mediated by ABCA1.

Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men.

OBJECTIVES: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. DESIGN: Double-blind, randomized, parallel, reference-controlled intervention study. SUBJECTS AND INTERVENTION: Seventy-one healthy males aged 31-69 y received one of the following treatments: (1). mixture of 50% c9,t11 CLA and 50% t10,c12 CLA isomers (CLA 50:50); (2). mixture of 80% c9,t11 CLA and 20% t10,c12 CLA isomers (CLA 80:20); and (3). sunflower oil fatty acids (reference). The treatments were given as supplements in softgel capsules providing a total of 1.7 g (c9,t11+t10,c12) CLA fatty acids (50:50) or 1.6 g (c9,t11+t10,c12) CLA glycerides (80:20) per day in treatment groups for 12 weeks. RESULTS: Almost twice as many subjects reached protective antibody levels to hepatitis B when consuming CLA 50:50 fatty acids (15/24, 62%) compared with subjects consuming the reference substance (7/21, 33%, P=0.075). In subjects consuming CLA 80:20 glycerides this was 8/22 (36%). Other aspects of immune function, ie DTH responses, NK cell activity, lymphocyte proliferation and production of TNF-alpha, IL1-beta, IL6, IFN-gamma, IL2, IL4, and PGE(2), were not affected. CONCLUSION: This is the first study that suggests that CLA may beneficially affect the initiation of a specific response to a hepatitis B vaccination. This was seen in the CLA 50:50, but not in the CLA 80:20 group.

Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels; a randomized, diet-controlled intervention study.

OBJECTIVE: To evaluate the effect of moderate alcohol consumption on the acute phase proteins C-reactive protein and fibrinogen. DESIGN: Randomized, diet-controlled, cross-over study. SETTING: The study was performed at TNO Nutrition and Food Research, Zeist, The Netherlands. SUBJECTS: Ten middle-aged men and 10 postmenopausal women, all apparently healthy, non-smoking and moderate alcohol drinkers, were included. One women dropped out because of a treatment-unrelated cause. The remaining 19 subjects finished the experiment successfully. INTERVENTIONS: Men consumed four glasses and women consumed three glasses of beer or no-alcohol beer (control) with evening dinner during two successive periods of 3 weeks. The total diet was supplied to the subjects and had essentially the same composition during these 6 weeks. Before each treatment there was a 1 week washout period to compensate for possible carry-over effects. RESULTS: Plasma C-reactive protein and fibrinogen levels were decreased by 35% (P=0.02) and 12.4% (P< or =0.001), respectively, after 3 weeks' consumption of beer, as compared to no-alcohol beer consumption. CONCLUSIONS: Moderate alcohol consumption significantly decreased plasma C-reactive protein and fibrinogen levels. An anti-inflammatory action of alcohol may help explain the link between moderate alcohol consumption and lower cardiovascular disease risk. SPONSORSHIP: Dutch Foundation for Alcohol Research (SAR).

Moderate consumption of beer, red wine and spirits has counteracting effects on plasma antioxidants in middle-aged men.

OBJECTIVE: To evaluate the in vivo effects of moderate consumption of red wine, beer and spirits on antioxidants, antioxidant enzymes and antioxidant capacity. DESIGN: Randomized, diet-controlled, cross-over study. SUBJECTS: Twelve apparently healthy, non-smoking middle-aged men were included; 11 of them completed the study. INTERVENTIONS: Each subject consumed four glasses of red wine, beer, spirits and water (negative control) with evening dinner during four successive periods of 3 weeks, daily at the Institute. The total diet was supplied to the subjects and had essential the same composition during these 12 weeks. RESULTS: Neither the enzyme activities of serum glutathion peroxidase, erythrocyte glutathion reductase and superoxide dismutase nor the plasma concentrations of alpha- and gamma-tocopherol, lutein, zeaxantin, beta-cryptoxanthin, lycopene and alpha-carotene were affected. Plasma beta-carotene concentrations were decreased after 3 weeks' consumption of red wine, beer and spirits (40 g alcohol/day) as compared to consumption of water, by 15% (P=0.0005), 11% (P=0.010) and 13% (P=0.003), respectively. Also, plasma ascorbic acid was decreased after beer (15%, P=0.004) and spirits (12%, P=0.030), but not after wine consumption. Serum uric acid concentrations were increased after consumption of beer (15%, P<0.0001), spirits (8%, P=0.008) and red wine (9%, P=0.003). The overall serum antioxidant capacity, assessed as Trolox equivalent antioxidant capacity (TEAC), was similar for all treatments. CONCLUSIONS: Moderate consumption of red wine, beer and spirits has counteracting effects on plasma antioxidant components, resulting in no significant effect on overall antioxidant status. The effects on antioxidant parameters are largely independent of the type of alcoholic beverage, and probably irrelevant to chronic disease risk. SPONSORSHIP: Dutch Foundation for Alcohol Research (SAR).

Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects.

OBJECTIVE: To investigate the dose-response relationship between cholesterol lowering and three different, relatively low intake levels of plant sterols (0.83, 1.61, 3.24 g/d) from spreads. To investigate the effects on lipid-soluble (pro)vitamins. DESIGN: A randomized double-blind placebo controlled balanced incomplete Latin square design using five spreads and four periods. The five study spreads included butter, a commercially available spread and three experimental spreads fortified with three different concentrations of plant sterols. SUBJECTS: One hundred apparently healthy normocholesterolaemic and mildly hypercholesterolaemic volunteers participated. INTERVENTIONS: Each subject consumed four spreads, each for a period of 3.5 week. RESULTS: Compared to the control spread, total cholesterol decreased by 0.26 (CI: 0.15-0.36), 0.31 (CI: 0.20-0.41) and 0.35 (CI: 0.25-0.46) mmol/L, for daily consumption of 0.83, 1.61 and 3.24 g plant sterols, respectively. For LDL-cholesterol these decreases were 0.20 (CI: 0.10-0.31), 0.26 (CI: 0.15-0.36) and 0.30 (CI: 0.20-0.41). Decreases in the LDL/HDL ratio were 0.13 (CI: 0.04-0.22), 0.16 (CI: 0.07-0.24) and 0.16 (CI: 0.07-0.24) units, respectively. Differences in cholesterol reductions between the plant sterol doses consumed were not statistically significant. Plasma vitamin K1 and 25-OH-vitamin D and lipid standardized plasma lycopene and alpha-tocopherol were not affected by consumption of plant sterol enriched spreads, but lipid standardized plasma (alpha + beta)-carotene concentrations were decreased by about 11 and 19% by daily consumption of 0.83 and 3.24 g plant sterols in spread, respectively. CONCLUSIONS: The three relatively low dosages of plant sterols had a significant cholesterol lowering effect ranging from 4.9-6.8%, 6.7-9.9% and 6.5-7.9%, for total, LDL-cholesterol and the LDL/HDL cholesterol ratio, respectively, without substantially affecting lipid soluble (pro)vitamins. No significant differences in cholesterol lowering effect between the three dosages of plant sterols could be detected. This study would support that consumption of about 1.6 g of plant sterols per day will beneficially affect plasma cholesterol concentrations without seriously affecting plasma carotenoid concentrations.

Retinoid metabolism and all-trans retinoic acid-induced growth inhibition in head and neck squamous cell carcinoma cell lines.

Retinoids can reverse potentially premalignant lesions and prevent second primary tumours in patients with head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been reported that acquired resistance to all-trans retinoic acid (RA) in leukaemia is associated with decreased plasma peak levels, probably the result of enhanced retinoid metabolism. The aim of this study was to investigate the metabolism of retinoids and relate this to growth inhibition in HNSCC. Three HNSCC cell lines were selected on the basis of a large variation in the all-trans RA-induced growth inhibition. Cells were exposed to 9.5 nM (radioactive) for 4 and 24 h, and to 1 and 10 microM (nonradioactive) all-trans RA for 4, 24, 48 and 72 h, and medium and cells were analysed for retinoid metabolites. At all concentrations studied, the amount of growth inhibition was proportional to the extent at which all-trans-, 13- and 9-cis RA disappeared from the medium as well as from the cells. This turnover process coincided with the formation of a group of as yet unidentified polar retinoid metabolites. The level of mRNA of cellular RA-binding protein II (CRABP-II), involved in retinoid homeostasis, was inversely proportional to growth inhibition. These findings indicate that for HNSCC retinoid metabolism may be associated with growth inhibition.

Production of eicosanoids and cytokines by Kupffer cells from young and old rats stimulated by endotoxin.

1. The clinicopathological features of endotoxaemia have been ascribed to cytotoxic mediators such as tumour necrosis factor, interleukins and eicosanoids. Macrophages, particularly Kupffer cells, are an important source of these mediators. Mortality from endotoxaemia is highly age related. 2. These studies focus on the role of hepatic Kupffer cells in the increased sensitivity of old rats to bacterial endotoxins. Possible age-related changes in the production of eicosanoids and induction of gene expression and secretion of interleukin 1, tumour necrosis factor and interleukin 6 were investigated in Kupffer cells derived from both young and old animals. 3. Basal production of biological response modifiers was low in cells of both young and old rats. Lipopolysaccharide stimulated production of the same types of monokines as described for other types of macrophages, although the pattern was specific for Kupffer cells. 4. Eicosanoids, predominantly prostaglandin D2 and prostaglandin F2 alpha, were produced mainly during the first hour after exposure to lipopolysaccharide. Endotoxin stimulated synthesis of mRNAs of interleukin 1, interleukin 6 and tumour necrosis factor alpha resulting in increased secretion of these cytokines into the medium. 5. Kupffer cells from both young and aged animals appear to be exquisitely sensitive to endotoxin in respect of expression of mRNA for both interleukin 1 alpha and interleukin 1 beta and less sensitive with respect to interleukin 6 and tumour necrosis factor alpha gene expression. At relatively high lipopolysaccharide concentrations interleukin 6 was secreted in particularly large amounts. 6. The effects of ageing on any of these responses of Kupffer cells were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in cytokeratin expression precede histological changes in epithelia of vitamin A-deficient rats.

Normal epithelial cell differentiation is characterized by the production of distinct cytokeratin proteins. It is well known that epithelia of several organs show squamous metaplasia in a vitamin A-deficient status. It is not yet known whether these histological changes are concomitant with a change in cytokeratin expression. Therefore, 3-week-old female rats (BN/BiRij) were fed a vitamin A-deficient diet for 8 weeks. The cytokeratin expression in epithelia of various organs was monitored immunohistochemically during the induction of vitamin A deficiency. Therefore, monoclonal antibodies specific for human cytokeratin 4, 5, 5 + 8, 7, 10, 14, 18 and 19 were used. In a normal vitamin A status, the distributional pattern for the different cytokeratins in rats was similar to that reported for human tissue. No change in cytokeratin expression was seen in trachea, skin, liver and colon at any time point studied. Squamous metaplasia in urinary bladder and salivary glands was observed after six weeks on the vitamin A-deficient diet. This was concomitant with a substitution of cytokeratins 4, 5 + 8, 7, 18 and 19 by cytokeratin 10. The latter cytokeratin is specific for keratinized squamous epithelium. A change in cytokeratin expression was observed in bladder, ureter, kidney, salivary glands, uterus and conjunctiva before histological alterations appeared. In conclusion, the changes in cytokeratin expression observed under vitamin A deficiency in epithelia in vivo are in agreement with those described in other studies for epithelial cells in vitro. The changes in cytokeratin expression and the subsequent differentiation into squamous cells occurs in basal cells of the bladder but not in transitional cells.(ABSTRACT TRUNCATED AT 250 WORDS)