Ethanol intake-induced apoptosis in glial cells and axonal disorders in the cerebellar white matter of UChA rats (voluntary ethanol consumers)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin-angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective ATI receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P) H oxidase-mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT(1)-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. (c) 2012 Elsevier Inc. All rights reserved.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 casecontrol studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.590.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.420.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.540.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.160.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Sugar intake is correlated with adiposity and obesity indicators and sedentary lifestyle in Brazilian individuals with morbid obesity

Obesity is a chronic disease characterized by increased accumulation of body fat. We evaluated the socioeconomic aspects, body composition, risk of metabolic complications associated with obesity, eating habits and lifestyle in both women and men adults and elderly with body mass index (BMI) 40 kg/m(2). Among the subjects studied, 79% (n = 32) are female, 5% (n = 2) smokers, 39% (n = 16) use alcohol and only 24% (n = 10) are practitioners of physical exercise. The higher food intake was breads, followed by rice. The daily intake of fruits and vegetables is low. Positive correlation between consumption of sugar and BMI and abdominal circumference (AC) was observed. In summary, was found that morbidly obese patients that looking for nutritional counseling presents increased body fat, poor eating habits and sedentary lifestyle.

Do Tobacco and Alcohol Modify Protective Effects of Diet on Oral Carcinogenesis?

Recent systematic reviews concluded that the frequent consumption of fruits and vegetables is inversely associated with the risk of oral cancer. We assessed this association, specifically comparing results obtained to nonsmokers and smokers, as well to nondrinkers and drinkers. We conducted a case-control study involving 296 patients with oral squamous cell carcinoma (cases) attended in 3 major hospitals of Sao Paulo, Brazil, paired with 296 controls, recruited from outpatient units of the same hospitals. Multivariate models assessed the effect of fruits and salads according to smoking and drinking. The intake of fruit was associated with the prevention of the disease in the specific assessment among light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27-0.78) and heavy (OR = 0.30; 95% CI = 0.14-0.65) smokers. The same was observed for vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22-1.12) or vegetable (for tomato, OR = 0.53; 95% CI = 0.31-0.93) was associated with reduced risk of oral and oropharyngeal cancer. Similar results were found in the stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30-0.87) and 0.18 for fruits (95% CI = 0.07-0.45), respectively, for light and heavy drinkers. This observation suggests that the protective effect of fruit and salad intake may modulate the deleterious effects from tobacco and alcohol.

Characterization of sialic acid index of plasma apolipoprotein J and phosphatidylethanol during alcohol detoxification--a pilot study

Apolipoprotein J (ApoJ) is a component of plasma high-density lipoproteins. Previous studies have shown progressive recovery of ApoJ sialic acid content with increased duration of alcohol abstinence. Therefore, the sialic acid index of plasma apolipoprotein J (SIJ) seems to be a promising alcohol biomarker. Phosphatidylethanol (PEth) is a direct ethanol metabolite and has recently attracted attention as a biomarker of prolonged intake of higher amounts of alcohol. The aim of the pilot study was to explore sensitivity, specificity, and normalization of SIJ and PEth in comparison with traditional and emerging biomarkers.

Assessment of Alcohol Reward in Prairie Voles (Microtus ochrogaster)

The purpose of our study was to assess whether prairie voles find alcohol rewarding. Prairie voles have recently become a species of interest for alcohol studies, which have traditionally used other rodent model species including several different strains of mice and rats. The prairie vole is one of only two known rodent species that readily administers high levels of unsweetened alcohol, implicating it as a potentially effective animal model for studying alcohol abuse. However, voluntary consumption does not necessarily imply that prairie voles find it rewarding. Therefore the purpose of our study was to investigate if alcohol has rewarding properties for prairie voles using three different approaches: place conditioning, flavor conditioning, and immunohistochemistry. Furthermore, we sought to characterize their reward profile and compare it to other commonly used rodent models ¿ C57BL/6 mice, DBA/2J mice, and Sprague-Dawley rats. Place and flavor conditioning are behavioral methods that rely on the learned association between a stimulus and the effects of a drug; the drug of interest in these studies is alcohol. To assess whether prairie voles will demonstrate a conditioned preference for alcohol-paired stimuli, seven place conditioning studies were run that investigated a range of different doses, individual conditioning session durations, and trial durations. Video analysis revealed no difference in the amount of time spent on the alcohol-paired floor, suggesting no conditioned place preference for alcohol. Two flavor conditioning tests were conducted to assess whether voles would demonstrate a preference for an alcohol-paired flavored saccharin solution. Voles demonstrated reduced consumption of the alcohol-paired flavored saccharin solution, regardless of dose or flavor, when alcohol administration occurred after conditioning sessions (p=<0.001). When alcohol was administered before conditioning sessions, no difference in consumption of the alcohol-paired and saline-paired flavored saccharin solutions was seen (p=0.545). Previous studies that have documented similar behavior have hypothesized that this is an example of an anticipatory contrast effect. This theory proposes that prairie voles reduce their intake of a hedonic solution (flavored saccharin solution) in anticipation of later drug administration (alcohol). However, conditioning-based behavioral methods of studying alcohol reward are highly sensitive to the parameters of the conditioned stimulus, thus it is possible that voles will not show preference for alcohol-related stimuli, even if they do find alcohol rewarding. Immunohistochemical analysis supplemented this behavioral data by allowing us to identify specific neural regions that were directly activated in response to the acute administration of alcohol. No difference in the number of activated c-Fos neurons in the Nucleus Accumbens (NAc) core or shell was seen (p=0.3364; p=0.6698) in animals that received an acute injection of alcohol or saline. There was a significant increase in the number of activated c-Fos neurons in the Paraventricular Nucleus of the Hypothalamus (PVN) in alcohol-treated animals compared to saline-treated animals (p=0.0034). There was no difference in the pixel count of activated c-Fos neurons or in the % area activated in the Arcuate Nucleus between alcohol and saline-treated animals (p=0.4523; p=0.3304). In conclusion, the place conditioning studies that were conducted in this thesis suggest that prairie voles do not demonstrate preference or aversion towards alcohol-paired stimuli. The flavor conditioning studies suggest that prairie voles do not demonstrate aversion but rather avoidance of the alcohol-paired flavor in anticipation of future alcohol administration. The preliminary immunohistochemical data collected is inconclusive but cannot rule out the possibility of neuronal activation patterns indicative of reward. Taken together, our data indicate that prairie voles hav

Determination of fatty acid ethyl esters in dried blood spots by LC-MS/MS as markers for ethanol intake: application in a drinking study.

The forensic utility of fatty acid ethyl esters (FAEEs) in dried blood spots (DBS) as short-term confirmatory markers for ethanol intake was examined. An LC-MS/MS method for the determination of FAEEs in DBS was developed and validated to investigate FAEE formation and elimination in a drinking study, whereby eight subjects ingested 0.66-0.84 g/kg alcohol to reach blood alcohol concentrations (BAC) of 0.8 g/kg. Blood was taken every 1.5-2 h, BAC was determined, and dried blood spots were prepared, with 50 μL of blood, for the determination of FAEEs. Lower limits of quantitation (LLOQ) were between 15 and 37 ng/mL for the four major FAEEs. Validation data are presented in detail. In the drinking study, ethyl palmitate and ethyl oleate proved to be the two most suitable markers for FAEE determination. Maximum FAEE concentrations were reached in samples taken 2 or 4 h after the start of drinking. The following mean peak concentrations (c̅ max) were reached: ethyl myristate 14 ± 4 ng/mL, ethyl palmitate 144 ± 35 ng/mL, ethyl oleate 125 ± 55 ng/mL, ethyl stearate 71 ± 21 ng/mL, total FAEEs 344 ± 91 ng/mL. Detectability of FAEEs was found to be on the same time scale as BAC. In liquid blood samples containing ethanol, FAEE concentrations increase post-sampling. This study shows that the use of DBS fixation prevents additional FAEE formation in blood samples containing ethanol. Positive FAEE results obtained by DBS analysis can be used as evidence for the presence of ethanol in the original blood sample. Graphical Abstract Time courses for fatty acid ethyl ester (FAEE) concentrations in DBS and ethanol concentrations for subject 1 over a period of 7 h. Ethanol ingestion occured during the first hour of the time course.

INTAKE VARIABLES AS PREDICTORS OF ASSESSMENT AND REFERRAL PROCEDURE OUTCOMES IN EMPLOYEE ASSISTANCE PROGRAMS

While reported prevalence rates of troubled employees vary considerably, even conservative estimates indicate a major public health problem. For example, alcohol and drug related problems alone cost U.S. industry more than 45 billion dollars annually.^ Of the alternatives available to deal with these problems, e.g., dismissal or disciplinary actions, the most viable and cost effective are employee assistance programs (EAP), designed to provide professional assistance to employees experiencing alcohol, drug, emotional or personal crisis.^ The principal component of an EAP is that of assessment and referral, and this study was developed to determine which EAP client intake variables are the most efficacious predictors of assessment and referral procedures.^ Although, specific client intake variables were statistically significant the discriminant classification analysis was demonstrably inadequate. Nevertheless, the identification of A/R procedure phases which were not efficacious, as well as EAP client populations for whom services were not effective, were extremely valuable discernments. Identifying the less efficacious components of the A/R process provided an opportunity to recommend alternatives to current program procedures and practices, which may ameliorate program effectiveness. ^

Prevalence of alcohol consumption and pattern of use among the elderly in the WHO European Region

BACKGROUND/AIMS: Alcohol-related problems are relevant in the elderly, particularly in developed countries, but there is a lack of cross-country comparisons. The present work aims to examine the frequency and patterns of alcohol consumption in older adults across different European countries, and to analyze the relationship between socioeconomic status and gender with alcohol consumption. METHODS: General population-based household surveys of randomly selected adults over 60 years of age in 14 European countries. PARTICIPANTS: 10,119 subjects [mean age: 70.4 (SD = 7.1)], 61.9% women. RESULTS: There are marked differences in alcohol consumption across countries. Except for three countries from eastern regions, most people in all countries present moderate consumption regarding the amount of alcohol and pattern of use. However, there are marked gender differences, with a higher intake in men (effect sizes ranging from 0.57 to 1.27), although these differences are relatively proportional across countries. Finally, a higher socioeconomic status is positively related (B = 0.845, 95% CI: 0.30/1.40) with alcohol consumption after controlling for gender, age, health-functioning status and the country's development level. CONCLUSIONS: There are marked differences in consumption of alcohol in the elderly between the different countries, and male gender, as well as a higher SES, were associated with higher alcohol consumption.

The importance of improving diet in 'Securing Scotland's Health': exploring differences in dietary intake between Scotland and England

Background: Various factors have been investigated to account for the higher premature death rates in Scotland compared to England. Higher levels of deprivation in Scotland provide a partial explanation for these differences but recent work comparing areas of the UK with similar deprivation profiles and low life expectancy has shown that this is not the only reason. One hypothesis yet to be tested adequately is differences in diet and nutrition. Objective: To conduct a comparative analysis of dietary intake between Scotland and England using pooled food purchase data from the Living Costs and Food Survey (LCFS) from 2001 to 2012 and to assess differences in equivalised income quintiles (controlling for survey year, age of household reference person, and age household reference person left full-time education). Results: Lower intakes of fruit and vegetables, oil rich fish, fibre, vitamin A, folate, vitamin C and vitamin D and higher intakes of red and processed meat, whole milk, butter, savoury snacks, confectionary, soft drinks, saturated fat and NMES (added sugar and sugar in fruit juice), sodium and alcohol were found for Scotland compared to England. Differences between Scotland and England were higher for those on lower incomes for dietary components known to be related to health outcomes. For example fruit consumption was 14g/day lower for the lowest income quintile compared to 4 g/day lower in the highest quintile for Scotland versus England. Conclusions: A poorer diet in Scotland compared to England, particularly among disadvantaged groups, is likely to be one of the reasons for excess mortality. The current evidence on the continued poor diet in Scotland, particularly in disadvantaged groups, should not be ignored. Identifying effective, culturally appropriate approaches to improve diet across the population and notably in the most deprived areas needs further investment. Funded by NHS Health Scotland. Data provided by DEFRA, ONS and the UK Data Archive.

ABSTINENCE AND ALCOHOL CONSUMPTION AMONG STUDENTS: THE INFLUENCE OF PERSONAL, FAMILY AND SOCIO-CULTURAL SPHERES

Introduction: Among young people, regular or alcohol abuse seems to ally with individual factors, which congregate to other generators behaviors health risk, in social environment, including family and school. The consumption of alcoholic beverages in the younger age groups, according to the World Development Report goes beyond 60%. In the Portuguese case, the Alentejo is the region that recorded higher consumption among schoolchildren. Objectives: This study aims to know the personal inluences of family, of belonging to the group and the school environment, on the withdrawal and consumption habits among young people. Methods: A qualitative nature of research, using comprehensive semi-structured interviews. The study was developed in a school district of Evora, Portugal. The sample consists of ten students from the 8th school grade, ive non-consumers-ive consumers aged between 13 and 15 years old. Results: The trial takes place between 12 and 14 years old as a result of curiosity, explicit or tacit motivation, “give style”, the environment, entertainment and observing behavior. Among the effects of intake indicated as motivators consumption highlight the joy of reaching states and willingness. Family members tend to encourage moderate drinking on festive occasions. family models exaggerated consumption repudiate ingestion. The elements of the group of belonging tend to motivate explicitly, the intake among consumers students. The school promotes initiatives on the theme, punctually. Conclusions: The consumption of alcohol among young people suffer the personal, family and belonging group inluences. The initiatives in school tend to have no effect.

Nat2, Xrcc1 And Hogg1 Polymorphisms, Cigarette Smoking, Alcohol Consumption And Risk Of Upper Aerodigestive Tract Cancer.

To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer. A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among never-drinkers (p=0.048). Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

Not Simply A Matter Of Fish Intake.

Background and aims: Recent findings have highlighted enhanced fish consumption as a potential measure to increase intake of healthy fatty acids, particularly omega-3. The generalizability of this recommendation, however, may fall short by differences in fish species and cooking techniques. Hence, we investigated how these 2 variables affect the lipid content in fish flesh. Methods and Results: Nine species of freshwater, deep sea or shore fish were grilled, steamed or fried with or without the addition of soybean oil, olive oil or butter. The lipid composition was analysed and a significant difference was observed in cholesterol, saturated fatty acids, polyunsaturated fatty acids, omega-3 fatty acids, and omega-6 fatty acids contents between species (p<0.05). The use of soybean or olive oil was associated with a significant change in flesh concentration of polyunsaturated, omega-3 and omega-6 fatty acids (p<0.05). Conclusion: This study calls attention to the specific lipid content that must be expected from different fish species and cooking techniques.

Nitric Oxide-releasing Poly(vinyl Alcohol) Film For Increasing Dermal Vasodilation.

Pathological conditions associated with the impairment of nitric oxide (NO) production in the vasculature, such as Raynaud's syndrome and diabetic angiopathy, have stimulated the development of new biomaterials capable of delivering NO topically. With this purpose, we modified poly(vinyl-alcohol) (PVA) by chemically crosslinking it via esterification with mercaptosuccinic acid. This reaction allowed the casting of sulfhydrylated PVA (PVA-SH) films. Differential scanning calorimetry and X-ray diffractometry showed that the crosslinking reaction completely suppressed the crystallization of PVA, leading to a non-porous film with a homogeneous distribution of -SH groups. The remaining free hydroxyl groups in the PVA-SH network conferred partial hydrophylicity to the material, which was responsible for a swelling degree of ca. 110%. The PVA-SH films were subjected to an S-nitrosation reaction of the -SH groups, yielding a PVA containing S-nitrosothiol groups (PVA-SNO). Amperometric and chemiluminescence measurements showed that the PVA-SNO films were capable of releasing NO spontaneously after immersion in physiological medium. Laser Doppler-flowmetry, used to assess the blood flow in the dermal microcirculation, showed that the topical application of hydrated PVA-SNO films on the health skin led to a dose- and time-dependent increase of more than 5-fold in the dermal baseline blood flow in less than 10min, with a prolonged action of more than 4h during continuous application. These results show that PVA-SNO films might emerge as a new material with potential for the topical treatment of microvascular skin disorders.