The stress-buffering role of alcohol consumption: the importance of symptom dimension

This paper examines the possibility of the existence of stress-buffering properties of alcohol consumption suggested by a recent study in which life events were related to depressive symptoms for abstainers and heavy drinkers but not for moderate drinkers. Survey data on affective and somatic symptoms from 364 urban and 333 rural Florida residents indicated some support for the buffering argument. Moderate and heavy drinkers manifested significantly lower levels of symptoms than did abstainers only with regard to somatic symptoms. Life event-drinking pattern interactions did not reach statistical significance, although trends consistent with the buffering hypothesis were obtained with the somatic symptom measure. Implications of the data are explored.     

Influence of acute alcohol intake and alcohol withdrawal on circulating levels of IL-6, IL-8, IL-10 and IL-12

Cytokine balance alterations are responsible for some of the systemic and hepatic manifestations of alcoholism. The present study was aimed to evaluate the influence of both acute alcohol abstinence (in alcoholics) and acute alcohol intake (in healthy subjects) on serum IL-6, IL-8, IL-10, and IL-12 levels. Serum cytokine concentrations were determined on admission and after a median of 6 days of ethanol abstinence in 29 patients with alcohol withdrawal syndrome. The same determinations were made in five healthy volunteers at baseline and after 36 h of a single 60 g-dose alcohol intake. Increased serum levels of IL-6, IL-10 and, to a lesser extent IL-8, declined in the few days after alcohol abstinence in patients with alcohol withdrawal syndrome. Serum IL-8 values increased after alcohol intake in healthy subjects. Rapid variation of serum cytokine levels along with alcohol intake or abstinence should be taken into account in cytokine studies in alcohol abusers.     

Serum markers of hepatocyte death and apoptosis are non invasive biomarkers of severe fibrosis in patients with alcoholic liver disease

Background

Quantification of hepatotocyte death is useful to evaluate the progression of alcoholic liver diseases. Our aims were to quantify and correlate the circulating levels of Cytokeratin 18 (CK18) and its caspases-generated fragment to disease severity in heavy alcoholics.

Methodology/Principal Findings

CK18 and CK18-fragment were evaluated in the serum of 143 heavy alcoholics. Serum levels of markers of hepatocyte death (CK18), apoptosis (CK18 fragment) and necrosis (CK18 -CK18 fragment) increased in patients with severe fibrosis compared to patients with mild fibrosis. These markers strongly correlated with Mallory-Denk bodies, hepatocyte ballooning, fibrosis and with hepatic TNFα and TGFβ assessed in the liver of 24 patients. Elevated levels of serum hepatocyte death and apoptotic markers were independent risk factors in predicting severe fibrosis in a model combining alkaline phosphatase, bilirubin, prothrombin index, hyaluronate, hepatocyte death and apoptotic markers. The level of markers of hepatocyte death and apoptosis had an area under the receiving operator curve that predicted severe fibrosis of 0.84 and 0.76, respectively.

Conclusion/Significance

Death of hepatocytes can be easily evaluated with serum markers and correlated with severe fibrosis in heavy alcohol drinkers. These biomarkers could be useful to rapidly evaluate liver injuries and the efficacy of therapies.     

Job strain and alcohol intake: a collaborative meta-analysis of individual-participant data from 140,000 men and women

Background

The relationship between work-related stress and alcohol intake is uncertain. In order to add to the thus far inconsistent evidence from relatively small studies, we conducted individual-participant meta-analyses of the association between work-related stress (operationalised as self-reported job strain) and alcohol intake.

Methodology and Principal Findings

We analysed cross-sectional data from 12 European studies (n = 142 140) and longitudinal data from four studies (n = 48 646). Job strain and alcohol intake were self-reported. Job strain was analysed as a binary variable (strain vs. no strain). Alcohol intake was harmonised into the following categories: none, moderate (women: 1–14, men: 1–21 drinks/week), intermediate (women: 15–20, men: 22–27 drinks/week) and heavy (women: >20, men: >27 drinks/week). Cross-sectional associations were modelled using logistic regression and the results pooled in random effects meta-analyses. Longitudinal associations were examined using mixed effects logistic and modified Poisson regression. Compared to moderate drinkers, non-drinkers and (random effects odds ratio (OR): 1.10, 95% CI: 1.05, 1.14) and heavy drinkers (OR: 1.12, 95% CI: 1.00, 1.26) had higher odds of job strain. Intermediate drinkers, on the other hand, had lower odds of job strain (OR: 0.92, 95% CI: 0.86, 0.99). We found no clear evidence for longitudinal associations between job strain and alcohol intake.

Conclusions

Our findings suggest that compared to moderate drinkers, non-drinkers and heavy drinkers are more likely and intermediate drinkers less likely to report work-related stress.     

慢性阻塞性肺疾病大鼠模型中痩素及白介素-8 的表达分析

目的:观察COPD大鼠模型中瘦素(leptin)、白细胞介素8(IL-8)的表达情况,分析其相关性,探讨leptin在COPD发生发展中的作用及意义.方法:36只雄性SD大鼠随机分为①健康对照组;②COPD模型1组:分别于第(1、14)d经气管内注入内毒素200ug,熏5％香烟(第1、14d除外),2h/d,共4周;③COPD模型2组:单纯熏5％香烟2h/d,共12周.观察肺组织病理变化,免疫组化法测定leptin、IL-8在支气管肺组织的表达情况,放免法测定血清leptin及IL-8浓度.结果:细胞因子leptin及炎性因子IL-8在支气管肺组织阳性表达.LPS联合熏烟诱导COPD1组支气管肺组织中leptin(52.67±04.72)和IL-8(59.56± 3.94)表达较单纯熏烟诱导COPD2组leptin(38.89± 2.57)和IL-8(55.22± 3.42)表达明显升高,P＜0.05,两组COPD大鼠模型支气管肺组织中leptin及IL-8表达较正常对照组leptin( 1690± 1.52)和IL-8 (28.00± 4.24)表达均明显增高,P＜0.05,COPD1组血清中leptin(3.26± 0.95)ng/mL和IL-8( 107.51±13.38 )pg/mL-较COPD2组中leptin(2.42± 0.69 )ng/mL和IL-8((94.07± 11.20)pg/mL明显增高,P＜0.05,两组COPD大鼠模型血清中leptin及IL-8浓度较正常对照组leptin(0.95±0.56)ng/mL和IL-8( 39.48± 6.35 )pg/mL浓度显著升高,P＜0.05.血清中Leptin与IL-8表达水平呈显著正相关(r值分别为0.72 0.67 0.84均P＜0.05).经过q检验,两两之间比较均有统计学意义.结论:leptin和IL-8均参与COPD炎症反应过程,并且具有相关性,LPS促进二者的表达.     

Genetic determinants of ethanol-induced liver damage

BACKGROUND: Although a clear correlation exists between cumulative alcohol intake and liver disease, only some of the alcohol abusers develop signs of ethanol-induced liver damage. To identify some of the genetic variations predisposing persons to alcoholic liver disease (ALD), a genetic study was performed in heavy drinkers from the cohort of the Dionysis study, a survey aimed at evaluating liver disease in the open population of two towns in Northern Italy (6917 individuals). MATERIALS AND METHODS: 158 heavy drinkers (approximately 85% of all heavy drinkers in the population; daily alcohol intake > 120 g in males and >60 g in females) were investigated by the analysis of nine polymorphic regions, mapping in exons III and IX of the alcohol-dehydrogenase (ADH)-2 gene, in exon VIII of the ADH3 gene, in intron VI, in the promoter region of the cytochrome P4502E1 (CYP2E1) gene, and in the promoter region of the tumor necrosis factor-alpha gene. RESULTS: Heavy drinkers with or without ALD significantly differed for the distribution of alleles of the cytochrome P4502E1 (CYP2E1) and alcohol-dehydrogenase-3 (ADH-3) genes. In one town, allele C2 in the promoter region of the CYP2E1 gene had a frequency of 0.06 in healthy heavy drinkers, of 0.19 in heavy drinkers with ALD (p = 0.012), and of 0.33 in heavy drinkers with cirrhosis (p = 0.033). In the other town, whose inhabitants have different genetic derivation, a prominent association between ALD and homozygosity for allele ADH3*2 of ADH3 was found, with a prevalence of 0.31 in heavy drinkers with ALD and of 0.07 in healthy heavy drinkers controls (p = 0.004). CONCLUSIONS. Both heterozygosity for allele C2 of CYP2E1 and homozygosity for allele ADH3*2 of ADH3 are independent risk factors for ALD in alcohol abusers. The relative contribution of these genotypes to ALD is dependent on their frequency in the population. Overall, heavy drinkers lacking either of these two genotypes are 3.2 and 4.3 times more protected from developing ALD and cirrhosis respectively.     

Alcoholgebruik onder 55-plussers in Nederland

In The Netherlands no detailed information about alcohol consumption among older persons (55 years and older) is available. Therefore we investigated the prevalence and determinants of alcohol consumption with data from the Longitudinal Aging Study Amsterdam. The results show that 13.4% of persons of 55 years and older are heavy drinkers (male >3 glasses per day, female >2 glasses per day). Most heavy drinkers are younger than 75 years of age, and in this age group more female (22.2%) than male (14.8%) are heavy drinkers. 13% of all participants frequently drinks 6 or more glasses in a short period of time (binge drinking). In the age group of 55-65 years alcohol consumption has considerably increased over a period of ten years. This increase is stronger among females than among males. When people grow older alcohol consumption decreases, which seems associated with a decline in physical or psychological health and/or cognitive decline. Heavy and binge drinking is associated with younger age, higher education and income, and may be strongly related to their social lifes.     

Maternal serum proinflammatory cytokines in preterm labor with intact membranes: neonatal outcome and histological associations

Our aim was to compare maternal serum concentrations of interleukin(IL)-1alpha IL-1beta, IL-6 and IL-8 in pregnancies complicated by preterm labor (PTL), with the levels in healthy controls at comparable gestational age, and to determine if these assays have any value in the prediction of early-onset neonatal infection or histological chorioamnionitis. The study population consisted of 65 women with new-onset PTL, and 31 healthy controls. Maternal serum concentrations of IL-6 (8.40 versus 3.30 pg/mL; p = 0.002) and IL-1beta (2.20 versus 0.50 pg/mL; p = 0.003) were significantly higher in patients with PTL as compared to healthy pregnant women. The IL-1beta concentration (13.60 versus 1.20 pg/mL; p = 0.02) was significantly higher in the serum of mothers whose babies developed early-onset infections, than in mothers of newborns that were healthy. However, its predictive value, and the value of the other cytokines studied, was poor. In addition, IL-1beta levels (28.79 versus 5.19 pg/mL; p = 0.001) were significantly higher in patients with histological chorionamnionitis, than in those without the condition,. The cut-off value of >or= 14 pg/mL predicted inflammatory changes with a sensitivity of 80%, specificity of 86%, PPV of 80% and NPV of 86%. IL-1beta seems to be of moderate value in the prediction of histological chorioamnionitis.     

Effect of alcohol on urinary and blood dolichols.

Alcohol appears to affect dolichol metabolism, as both serum and urinary dolichol concentrations were found to be significantly higher in alcoholics than in social drinkers. Furthermore, acute heavy drinking (5.5 g alcohol/kg body weight during 42 h) increased urinary dolichol excretion significantly, whereas moderate drinking (60 g/day for 10 days) had no effect. Increased urinary dolichol concentrations in alcoholics returned rapidly to normal with a half-life decay of 3 days, whereas increased serum dolichol concentrations did not change during a 7-day observation period. The mechanism behind alcohol-induced alterations in dolichol metabolism remains unclear, but based on our results, it seems likely that serum and urinary dolichols are regulated independently from each other.     

Stopping drinking and risk of oesophageal cancer.

OBJECTIVE--To examine the effect of stopping drinking on the risk of oesophageal cancer. DESIGN--Hospital based case-control study. SETTING--Surgical departments of four district general hospitals and general practices in Hong Kong. SUBJECTS--Cases were 400 consecutive admissions of patients with histologically confirmed diagnosis of oesophageal cancer during a 21 month period in 1989-90 (87% response rate). Controls were 1598 patients selected from the same surgical departments as the cases and from the general practices from which the cases were originally referred (95% response rate). MAIN OUTCOME MEASURE--Relative risk of developing oesophageal cancer after stopping drinking (adjusted for age, education, place of birth, smoking, and diet). RESULTS--Current light drinking (< 200g ethanol/week) was not associated with significant increase in risk. Among former drinkers risk fell more quickly in moderate (200-599 g/week) than heavy (> or = 600 g/week) drinkers. Even among heavy drinkers, however, risk had dropped substantially after five to nine years of not drinking. The results suggest that the time taken for risk to return to that in subjects who never drink was 10-14 years for moderate drinkers and 15 years or more, if ever, for heavy drinkers. CONCLUSION--Risk of oesophageal cancer decreases fairly rapidly with time after abstaining from drinking. This new finding could be used in health promotion to encourage behavioural changes, especially in heavy drinkers, who have a very high risk of developing oesophageal cancer. It also suggests that alcoholic beverages have a strong effect on the late stage of carcinogenesis.     

Drinking Pattern,Abstention and Problem Drinking as Risk Factors for Depressive Symptoms: Evidence from Three Urban Eastern European Populations

Purpose

To examine whether the frequency and amount of alcohol consumed in binge drinking sessions, total annual volume of alcohol consumed, problem drinking and abstaining from alcohol are associated with depressive symptoms in Eastern Europe.

Subjects and Methods

Cross-sectional data from a total of 24,381 participants from general population samples of the Czech Republic (N = 7,601), Russia (N = 6,908) and Poland (N = 9,872) aged 45–69 years in 2002–2005. Depressive symptoms were defined as ≥16 points on the Centre for Epidemiological Studies – Depression (CES-D) scale. Several alcohol related measures were derived using responses from the graduated frequency questionnaire. Binge drinking was defined at several sex-specific thresholds (ranging from 60+ to 140+ g of ethanol) and two frequencies (at least monthly or weekly). Total annual alcohol intake in grams was also extracted. Problem drinking was defined as ≥2 positive answers on the CAGE questionnaire.

Results

Problem drinking was consistently associated with approximately a 2-fold increase in odds of depressive symptoms across all countries and in both sexes. Abstaining from alcohol was typically associated with increased odds of depressive symptoms. Analyses separating lifelong abstainers and former drinkers in the Russian cohort revealed that this increased odds was driven by former drinkers. Amongst men, heavy frequent binge drinking was associated with increased odds of depressive symptoms in the Czech Republic and Poland. In women, heavy infrequent binge drinking was associated with increased odds of depressive symptoms in Russia and Poland. Only in Polish men was higher annual volume of alcohol intake associated with increased odds of depressive symptoms.

Conclusion

Abstaining from alcohol and problem drinking were associated with increased odds of depressive symptoms in these Eastern European populations. Annual volume of alcohol intake as well as frequency and amount of alcohol consumed in a binge drinking session were less consistently associated with depressive symptoms.     

Enhanced proinflammatory response of mononuclear cells to in vitro LPS-challenge in patients with ventricular fibrillation in the setting of acute myocardial infarction

Aims. Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death. A potential role of intrinsic, subclinical inflammatory states in patients suffering from ischemia-related VF has not been investigated yet. The aim of the present study was (i) to examine serum levels of proinflammatory markers in VF survivors and (ii) to evaluate basal and lipopolysaccharide (LPS)-stimulated interleukin-8-mRNA (IL-8-mRNA) levels in patients with and without VF complicating AMI. Methods. Twenty-five patients with a history of VF during AMI and a control group of 25 AMI patients without VF were included. Blood samples were taken remote from AMI with a mean of 590 days. Circulating serum levels of IL-8, IL-6, soluble E-selectin (sE-selectin), tissue factor activity (TFA), tissue inhibitor of matrix-metalloproteinase-1 (TIMP-1) and matrix-metalloproteinase-9 (MMP-9) were measured. Mononuclear cells were isolated by density gradient centrifugation. The cells were stimulated with lipopolysaccharide (LPS) from Escherichia coli (700 ng/mL). IL-8-mRNA levels in mononuclear cells were determined by a colorimetric mRNA quantification assay. Results. Serum levels (median; range) of IL-8 (VF: 2.24 pg/mL; <0.10–19.3 pg/mL versus controls: 0.10 pg/mL; <0.10–7.7 pg/mL; p = 0.014), IL-6 (VF: 0.68 pg/mL; <0.05–2.9 pg/mL versus controls: 0.23 pg/mL; <0.05–1.8 pg/mL; p = 0.042) and TIMP-1 (VF: 229 ng/mL; 144–348 ng/mL versus controls: 186 ng/mL; 126–263 ng/mL; p = 0.014) were significantly higher among patients with VF as compared to controls. Baseline IL-8-mRNA concentrations of blood mononuclear cells were significantly higher among patients with VF (257 amol/mL; 52–2672 amol/mL) as compared to patients without VF (37 amol/mL, 3.2–770 amol/mL; p < 0.01). IL-8-mRNA levels after LPS-challenge were significantly higher among patients with VF (3503 amol/mL; 215–13,573 amol/mL) than in patients without VF (1003 amol/mL; 208–3386 amol/mL; p < 0.01). Conclusions. Circulating IL-8, IL-6, and TIMP-1 concentrations as well as IL-8-mRNA expression in mononuclear cells at baseline and after LPS-challenge are increased among patients with a history of VF in the setting of AMI as compared to patients without VF. These findings indicate an enhanced inflammatory response to a proinflammatory stimulus in VF survivors. The magnitude of this increased acute phase reactants may indicate a novel pathway of arrhythmogenesis in patients with AMI.     

Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity

BACKGROUND: Psoriatic plaques have been shown to contain increased levels of proinflammatory cytokines. Serum levels of interleukin (IL)-6, IL-7, IL-8, and interferon (IFN)-gamma have been reported elevated in psoriatic patients. AIM: To evaluate serum cytokine profiles in psoriasis patients by improved enzyme-linked immunosorbent assay (ELISA) technique and to correlate these levels with disease severity. METHODS: We analyzed single serum samples from 10 patients with active untreated psoriasis, two patients with active treated psoriasis, and five healthy volunteers for major T helper type 1 and T helper type 2 cytokines using the LINCOplex ELISA multi-analyte detection system that permits simultaneous detection of multiple cytokines from a single sample. The disease severity, including erythema, induration, scale, and surface area, was assessed. RESULTS: IFN-gamma was markedly elevated in all sera from psoriasis patients, 33.8 +/- 1.3 pg/ml (mean +/- standard error) versus 8 +/- 1.5 pg/ml for normal controls (p < 0.01), and positively correlated with all indices of disease severity (Spearman r > 0.6). IL-8 was also increased in psoriasis patients (24.4 +/- 1.8 pg/ml) versus normal controls (3.6 +/- 1.2 pg/ml) (p < 0.05) and positively correlated with the degree of erythema (Spearman r > 0.6). Mean IL-12 levels were decreased in sera from psoriasis patients (8.5 +/- 1.2 pg/ml) compared with normal controls (42.2 +/- 5.3 pg/ml) (p < 0.01). Also, serum IL-10 levels were below detection levels in psoriatics compared with controls (6.4 +/- 1.3 pg/ml). CONCLUSIONS: This new ELISA system allowed rapid and reliable detection of numerous cytokines in single serum samples from patients with psoriasis. We observed that IFN-gamma and IL-8 cytokines were elevated in psoriatics and correlated with parameters of disease severity while IL-10 and IL-12 were decreased.     

Alcohol and blood pressure: the INTERSALT study.

OBJECTIVES--To assess the relation between alcohol intake and blood pressure in men and women and in men at younger and older ages; to examine the influence of amount and pattern of alcohol consumption, as well as of acute effects, taking into account body mass index, smoking, and urinary sodium and potassium excretion. DESIGN--Subjects reported alcohol consumption for each of seven days before standardised blood pressure measurement, and whether they had consumed any alcohol in the 24 hours before measurement. SETTING--50 centres worldwide. SUBJECTS--4844 men and 4837 women aged 20-59. MAIN OUTCOME MEASURES--Effect of alcohol on blood pressure estimated by taking a weighted average of regression coefficients from centres. Acute effect assessed by examining mean differences in blood pressure of non-drinkers and of heavy drinkers who had and had not consumed alcohol in the 24 hours before measurement. Effect of pattern of consumption assessed by examining mean differences in blood pressure of non-drinkers compared with drinkers (i) whose intake was concentrated in fewer days or who were drinking more frequently, and (ii) whose alcohol intake varied little over the seven days or varied more substantially, as indicated by the standard deviation of daily consumption. RESULTS--Of the 48 centres in which some people reported consuming at least 300 ml/week of alcohol, 35 had positive regression coefficients linking heavy alcohol consumption to blood pressure. Overall, alcohol consumption was associated with blood pressure, significantly at the highest intake. After account was taken of key confounders, men who drank 300-499 ml alcohol/week had systolic/diastolic blood pressure on average 2.7/1.6 mmHg higher than non-drinkers, and men who drank > or = 500 ml alcohol/week had pressures of 4.6/3.0 mmHg higher. For women, heavy drinkers (> or = 300 ml/week) had blood pressures higher by 3.9/3.1 mmHg than non-drinkers. Heavy drinking and blood pressure were strongly associated in both sexes, and in men at both younger (20-39 years) and older (40-59 years) ages. In men who were heavy drinkers, episodic drinkers (those with great variation in daily alcohol consumption) had greater differences in blood pressure compared with non-drinkers than did regular drinkers of relatively constant amounts. CONCLUSION--The significant relation of heavy drinking (3-4 or more drinks/day) to blood pressure, observed in both men and women, and in younger and older men, was independent of and added to the effect on blood pressure of body mass index and urinary excretion of sodium and potassium. The findings indicate the usefulness of targeting those at high risk as well as the general population to reduce the adverse effects of alcohol on blood pressure.     

Alcohol Consumption in Midlife and Cognitive Performance Assessed 13 Years Later in the SU.VI.MAX 2 Cohort

Background

Associations between alcohol consumption and cognitive function are discordant and data focusing on midlife exposure are scarce.

Objective

To estimate the association between midlife alcohol consumption and cognitive performance assessed 13 y later while accounting for comorbidities and diet.

Methods

3,088 French middle-aged adults included in the SU.VI.MAX (1994) study with available neuropsychological evaluation 13 y later. Data on alcohol consumption were obtained from repeated 24h dietary records collected in 1994–1996. Cognitive performance was assessed in 2007–2009 via a battery of 6 neuropsychological tests. A composite score was built as the mean of the standardized individual test scores (mean = 50, SD = 10). ANCOVA were performed to estimate mean differences in cognitive performance and 95% confidence intervals (CI).

Results

In women, abstainers displayed lower cognitive scores than did low-to-moderate alcohol drinkers (1 to 2 drinks/day) (mean difference = −1.77; 95% CI: −3.29, −0.25). In men, heavy drinkers (>3 drinks/day) had higher cognitive scores than did low-to-moderate (1 to 3 drinks/day) (mean difference = 1.05; 95% CI: 0.10, 1.99). However, a lower composite cognitive score was detected in male drinkers consuming ≥90 g/d (≈8 drinks/d). A higher proportion of alcohol intake from beer was also associated with lower cognitive scores. These associations remained significant after adjustment for diet, comorbidities and sociodemographic factors.

Conclusion

In men, heavy but not extreme drinking was associated with higher global cognitive scores. Given the known harmful effects of alcohol even in low doses regarding risk of cancer, the study does not provide a basis for modifying current public health messages.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00272428","term_id":"NCT00272428"}}NCT00272428     

Serum Hepatic Enzyme Activity and Alcohol Drinking Status in Relation to the Prevalence of Metabolic Syndrome in the General Japanese Population

Background

Studies on the combined associations of elevated serum hepatic enzyme activity and alcohol drinking with metabolic syndrome are rare. Our objectives were to evaluate the associations of elevated serum hepatic enzyme activity with the prevalence of metabolic syndrome in the general Japanese population and whether alcohol drinking had a modifying effect on these associations.

Methods

We conducted a cross-sectional study with 1,027 men and 1,152 women throughout Japan during 2002–2010. Biochemical factors including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were determined in overnight fasting blood, and a survey on lifestyle was conducted by questionnaire. Serum ALT and GGT levels were divided into tertiles in men and women, and their associations with the prevalence of metabolic syndrome were evaluated by logistic regressions.

Results

Elevated serum ALT and GGT, even within the reference range, were independently associated with increased metabolic syndrome prevalence and were associated with most of its components in both sexes, except for the association between GGT and low high-density lipoprotein (HDL) cholesterol in men. Stratified analyses by alcohol drinking status revealed that within the same tertile category of serum ALT and GGT, subjects classified as alcohol abstainers showed higher adjusted odds ratios for metabolic syndrome prevalence than those classified as regular alcohol drinkers in both sexes. The interaction effects of serum GGT with alcohol drinking status on metabolic syndrome prevalence were significant in both sexes.

Conclusions

These results suggest that elevated serum ALT and GGT, even within the reference range, are independently associated with increased metabolic syndrome prevalence, especially in alcohol abstainers, in Japanese men and women.     

Use of a questionnaire in general practice to increase the recognition of patients with excessive alcohol consumption.

A self administered questionnaire, the health survey questionnaire, was designed to detect excessive alcohol consumption and mailed to patients who were registered with two general practices. Replies were received from 2572(75%) of 3452 patients. Excessive consumption was taken as 42 units of alcohol per week or more for men and 21 units per week or more for women: 1 unit = approximately 10 g ethanol and is equivalent to a half pint of beer, one glass of wine, or one standard measure of spirits. One hundred and twenty men (11%) and 68 women (5%) were identified by their responses to the questionnaire as excessive drinkers. According to their responses, roughly half of these expressed some concern about their drinking. In the practice where a disease register was kept 18 patients had been recorded as heavy drinkers before the study, and an additional 74 were detected by the questionnaire. Within 12 months after the questionnaire survey three groups of respondents were reviewed: (a) the excessive drinkers, (b) those who indicated concern about drinking but did not exceed the limits for excessive consumption, and (c) a random sample of those who were in neither of these two categories. Patients in these three groups were interviewed in a standard fashion to determine their alcohol consumption. Breath alcohol measurement was also carried out and a blood sample taken for the estimation of mean cell volume, gamma glutamyltranspeptidase activity, and serum aspartate transaminase activity. There were highly significant correlations between estimates of consumption obtained by the questionnaire and those obtained at interview except among the women who were excessive consumers, whose responses to the questionnaire indicated levels of consumption that were much higher than those to which they admitted at interview. Stated weekly consumption at interview that was above the limits set for the study was used as the standard measure for comparing the questionnaire with the other indicators of excessive drinking. The questionnaire had a considerably greater estimated sensitivity in detecting male excessive consumers than any of the blood tests. Among the women it apparently performed less well, although the numbers stating excessive consumption at interview were small. Breath alcohol measurement was positive in only a few of the excessive drinkers. The use of this simple and inexpensive instrument is likely to prove widely acceptable to patients in general practice and should result in a considerable increase in the recognition by general practitioners of patients with excessive alcohol consumption.     

Correlation between levels of selected cytokines in cervico-vaginal fluid of women with abnormal vaginal bacterial flora

The aim of this study was to evaluate the rise of the levels of proinflammatory cytokines - IL-1alpha, IL-1beta, IL-6 and IL-8 in vagina of women with bacterial vaginosis (BV) and if there is any relationship between this levels. One hundred and twenty females between 22nd and 36th week of pregnancy were enrolled in the study. According to the bacterial flora of cervico-vaginal fluid evaluated by Gram stain, all women were divided into three groups. Group I (53 females; 44.2%)--normal bacterial flora, group II (35 females; 29.2%)--intermediate flora, and group with BV (32 females; 26.6%). The level of IL-1b in women with BV was over twelve times higher than in women from I group (131.35 and 10.6 pg/mL respectively). The next was the level of IL-1alpha--about seven times higher (128.45 vs 19.1 pg/mL) and the levels of IL-6 and IL-8, which were 1.7 times higher (16.2 vs 9.7 pg/mL and 656.7 vs 375.3 pg/mL respectively). Except for IL-6 these differences of levels were statistically significant (p<0.05). The levels of IL-1beta in group of women with BV correlated strongly with levels of IL-1alpha (r=0.72; p<0.0001) and weakly with levels of IL-6 (r=0.31; p=0.017). The correlation coefficient between levels of IL-6 and IL-8 rose gradually in II and BV group and reached levels r=0.575; p=0.0014 and r=0.67; p=0.0009 respectively. Our findings show that in vagina of women with BV the levels of proinflammatory cytokines rise, and that the rise of levels is in certain cases correlated.     

The osteopontin level in liver, adipose tissue and serum is correlated with fibrosis in patients with alcoholic liver disease

Background

Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.

Methodology/Principal Findings

OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.

Conclusion/Significance

OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.     

Cholesterol efflux to high-density lipoproteins and apolipoprotein A-I phosphatidylcholine complexes is inhibited by ethanol: role of apolipoprotein structure and cooperative interaction of phosphatidylcholine and cholesterol

There is a substantial body of evidence showing that moderate alcohol consumption is associated with a reduced risk of cardiovascular morbidity and mortality. One of the factors thought to contribute to this reduction in risk is an increase in the level of high-density lipoproteins (HDL) correlated with alcohol consumption. However, HDL levels are elevated in heavy drinkers, but their risk of vascular disease is greater compared with that of moderate drinkers. Ethanol at concentrations observed in heavy drinkers and alcoholics may directly act on HDL and apolipoproteins and in turn modify cholesterol efflux. In this paper, we show that ethanol significantly inhibited cholesterol efflux from fibroblasts to HDL and to apolipoprotein A-I (apoA-I) complexed with phosphatidylcholine (PC). Ethanol significantly inhibited binding of PC to apoA-I, inhibited incorporation of cholesterol only when apoA-I contained PC, and did not alter incorporation of cholesterol into HDL. ApoA-I structure was altered by ethanol as monitored by steady-state fluorescence polarization of tryptophan residues. The absence of ethanol effects on incorporation of cholesterol into HDL versus inhibition of cholesterol incorporation into the apoA-I-PC complex suggests that the effects of ethanol on cholesterol efflux mediated by HDL involve interaction with the cell surface and that efflux mediated by the apoA-I-PC complex is a combination of aqueous diffusion and contact with the cell surface. In addition, effects of ethanol on apoA-I suggest that pre-beta-HDL or lipid-free apoA-I may be more perturbed by ethanol than mature HDL, and such effects may be pathophysiological with respect to the process of reverse cholesterol transport in heavy drinkers and alcoholics.