WorldWideScience

Sample records for experimental chronic alcoholism

  1. Alcoholic Beverage Consumption and Chronic Diseases

    National Research Council Canada - National Science Library

    Zhou, Yue; Zheng, Jie; Li, Sha; Zhou, Tong; Zhang, Pei; Li, Hua-Bin

    2016-01-01

    Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity...

  2. Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

    Directory of Open Access Journals (Sweden)

    Godwin Sokpor

    2012-05-01

    Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

  3. [The morphometric characteristics of the main structural components of renal nephrons in the white rats with experimentally induced acute and chronic alcohol intoxication].

    Science.gov (United States)

    Shcherbakova, V M

    2016-01-01

    The objective of the present work was to study the morphometric characteristics of the main structural components of renal nephrons in the white rats with the experimentally induced acute and chronic alcohol intoxication. We undertook the morphometric examination of the structural elements of rat kidneys with the subsequent statistical analysis of the data obtained. The results of the study give evidence of the toxic action of ethanol on all structural components of the nephron in the case of both acute and chronic alcohol intoxication. The study revealed some specific features of the development of pathological process in the renal tissue structures at different stages of alcohol intoxication. The most pronounced morphological changes were observed in the renal proximal tubules and the least pronounced ones in the structure of the renal glomeruli. The earliest morphological changes become apparent in distal convoluted tubules of the nephron; in the case of persistent alcoholemia, they first develop in the renal corpuscles and thereafter in the distal proximal tubules. The maximum changes occur in the case of acute alcohol intoxication and between 2 weeks and 2 months of chronic intoxication; they become less conspicuous during a later period.

  4. Alcoholic Beverage Consumption and Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Yue Zhou

    2016-05-01

    Full Text Available Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity. The impact of drinking is usually dose-dependent, and light to moderate drinking tends to lower risks of certain diseases, while heavy drinking tends to increase the risks. Besides, other factors such as drinking frequency, genetic susceptibility, smoking, diet, and hormone status can modify the association. The amount of ethanol in alcoholic beverages is the determining factor in most cases, and beverage types could also make an influence. This review summarizes recent studies on alcoholic beverage consumption and several chronic diseases, trying to assess the effects of different drinking patterns, beverage types, interaction with other risk factors, and provide mechanistic explanations.

  5. Muscle histochemistry in chronic alcoholism

    Directory of Open Access Journals (Sweden)

    M. L. Ferraz

    1989-06-01

    Full Text Available Twenty-two chronic acoholic patients were assessed by neurologic examination and muscle biopsy. The patients manifested proximal muscular weakness to a variable extent. One case presented as an acute bout of myopathy, according to the Manual Muscle Test, MMT. The most prominent histologic feature observed was muscle atrophy (95.3% better evidenced through the ATPase stain with the predominance of type II A fibers (71.4%. Lack of the mosaic pattern (type grouping seen in 76% of the cases and an important mitochondrial proliferation with intrasarcoplasmatic lipid accumulation in 63% of the patients. In case of acute presentation of muscle weakness the. pathological substrate is quite different, i.e. presence of myositis mainly interstitial characterized by lymphoplasmocytic infiltrate and several spots of necrosis like Zencker degeneration. Based on histologic criteria, our data suggest that: the main determinant of muscle weakness seen in chronic alcoholic patients is neurogenic in origin (alcoholic polineuropathy; the direct toxic action of ethanol under the skeletal muscle is closely related to the mitochondrial metabolism; the so-called acute alcoholic myopathy has probably viral etiology.

  6. Management of Chronic Alcoholism in Nigeria | Oghagbon ...

    African Journals Online (AJOL)

    Man started consuming alcohol a long time ago, and it has become widely available since then. Consequently, the adverse effects of alcohol usage on the individual abuser and society have become prominent. In spite of this, the required proper management knowledge of the chronic alcoholics is sparse in our ...

  7. Neuromuscular disorders in chronic alcohol intoxication

    Directory of Open Access Journals (Sweden)

    A. Yu. Emelyanova

    2015-01-01

    Full Text Available The paper reviews the present-day Russian and foreign literature on neuromuscular disorders in chronic alcohol intoxication. The most common manifestations of alcohol disease include alcoholic polyneuropathy (PNP and alcohol-induced skeletal muscle injury. The clinical polymorphism of alcoholic PNP is discussed. The paper considers a chronic sensory automatic form due to the direct toxic effects of ethanol and its metabolites during long-term alcohol intoxication, as well as acute/subacute sensorimotor neuropathy, the basis for the pathogenesis of which is B group vitamins, predominantly thiamine, deficiency that develops in the presence of drinking bouts concurrent with malnutrition and/or alcohol-related gastrointestinal tract diseases. In addition to nonuse of alcohol and a properly balanced diet, antioxidant therapy with alphalipoic acid and neurotropic B group vitamins is considered to be pathogenetic therapy for neuropathy. The most common and least studied clinicalform of alcohol-induced musculoskeletal injury is chronic alcoholic myopathy (AM, the diagnostic standard for which is morphometricand immunohistochemical examination of a muscle biopsy specimen. The morphological base for this form of myopathy is predominantly type 2 muscle fiber atrophy caused by impaired protein synthesis and a decreased regenerative potential of muscle fiber. The efficacy of antioxidants and leucine-containing amino acid mixtures in the treatment of chronic AM is discussed.

  8. Haematological Profile In Chronic Alcohol Consumers | Stanly ...

    African Journals Online (AJOL)

    Background: Problem drinkers conceal the fact that they are chronic alcoholics, when giving a medical history. Laboratory studies on those who abuse alcohol in this environment are scarce as most studies are behavioral research. Routine haematolgical indices were studied in problem drinkers to help in the diagnosis of ...

  9. Damage of hippocampal neurons in rats with chronic alcoholism

    OpenAIRE

    Du, Ailin; Jiang, Hongbo; Xu, Lei; An, Na; Liu, Hui; Li, Yinsheng; Zhang, Ruiling

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons i...

  10. Characteristics of heart rate variability in alcohol-dependent subjects and nondependent chronic alcohol users.

    Science.gov (United States)

    Karpyak, Victor M; Romanowicz, Magdalena; Schmidt, John E; Lewis, Kriste A; Bostwick, John M

    2014-01-01

    Heart rate variability (HRV) is an objective and sensitive measure of integrated physiological functioning reflective of heart rhythm responsivity to internal and external demands. Reduced HRV is associated with vulnerability to stress and deterioration of medical and/or psychiatric conditions, while increased HRV is associated with a favorable treatment response and recovery from various medical and/or psychiatric conditions. Our previous review found that acute alcohol consumption caused decreased parasympathetic and increased sympathetic HRV effects in both nonalcoholic and chronic alcohol users. This review investigates the effects of chronic alcohol consumption on HRV in alcohol-dependent subjects and nondependent users. MEDLINE, Scopus, and PubMed were searched for human experimental and clinical trials that measured the effects of chronic alcohol use on HRV. Only publications that included a description of their study designs and clearly stated methodologies for data collections, and outcome measures were reviewed. We have reviewed a total of 24 articles. In nondependent users, low dose (approximating the recommended daily amount of 1 standard drink in women and 2 in men) use is associated with increased HRV parameters compared to those who drink less frequently or abstain altogether. A further increase in consumption is associated with decreased HRV compared to both abstainers and more moderate drinkers. HRV changes during withdrawal generally follow the same negative direction but are more complex and less understood. In dependent subjects, an improvement in HRV was seen following abstinence but remained reduced compared to nonalcoholic controls. This review demonstrates that HRV changes associated with chronic use follow a J-shaped curve. It supports recommendations that limit daily alcohol intake to no more than 2 drinks for men and 1 drink for women. Future studies should investigate HRV as a biomarker of alcoholism development and treatment response as

  11. Craving shift in chronic alcoholics.

    Science.gov (United States)

    Junghanns, K; Veltrup, C; Wetterling, T

    2000-06-01

    In order to investigate changes in the consumption of substances that stimulate the reward system, 222 recently detoxified alcoholics were asked about their consumptional habits before as compared to after detoxification (mixed prospective and retrospective design). Seventy-eight point two percent reported an increase in consumption of coffee, cigarettes, chocolate and other sweets, while 34.9% managed to reduce at least one of these substances. The increase was significant for coffee, chocolate and other sweets. The desire for consumption of these substances was correlated with the maximum ever experienced desire for alcohol (0.232 for coffee, 0.213 for cigarettes, 0.193 for chocolate and 0.176 for other sweets), and the actual consumption of coffee, cigarettes and sweets was correlated with the actual desire for alcohol (0.172, 0.157 and 0.245, respectively). The results lend some support to the hypothesis that psychotropic substances might serve as a kind of self-regulation against craving in this group. A possible link to biochemical theories is discussed. Copyright 2000 S. Karger AG, Basel.

  12. Chronic alcohol consumption from adolescence to adulthood in mice — effect on growth and social behavior

    OpenAIRE

    Zou, Hong; Xie, Qinglian; Zhang, Manfang; Zhang, Chenghao; Zhao, Guoping; Jin, Meilei; Yu, Lei

    2009-01-01

    Experimentation with alcohol is common during adolescence. However the long-term consequences from moderate alcohol use during adolescence development are not clear. Using a two-bottle free-choice paradigm in the home cage setting, we studied adolescent mice (4 weeks old) across a 6-week time span of the adolescence-to-adulthood development period. Adolescent mice readily reached a steady level of alcohol consumption and maintained this level throughout the 6-week period. Chronic alcohol cons...

  13. Chronic alcohol drinking: Liver and pancreatic cancer?

    Science.gov (United States)

    Zakhari, Samir

    2015-09-01

    Cancer is a multifactorial disease that results from complex interactions of numerous risk factors - genetic and environmental - over time, eventually leading to the diseased phenotypes. Thus, while epidemiological studies can point to risk factors, they cannot determine cause and effect relationships, and are unable to give biological and clinical insights into carcinogenesis. The link between any risk factor and carcinogenesis needs to be validated in experimental models. This is particularly true in epidemiological studies on alcohol consumption and its consequences. While there is no doubt that heavy alcohol consumption has devastating health effects, the inconsistencies in alcohol-related epidemiological studies and cancer suffer from possible sources of the variability in outcomes, ranging from inaccuracy of self-report of consumption to the problem of correlating cancer that started decades earlier to current or recent alcohol consumption. To further study the interactions between alcohol and cancer, the use of "Molecular Pathological Epidemiology" (MPE) advocated by Ogino et al. for dissecting the interplay between etiological factors, cellular and molecular characteristics, and disease progression in cancer is appropriate. MPE does not consider cancer as a single entity, rather it integrates analyses of epidemiological studies with the macroenvironment and molecular and microenvironment. This approach allows investigating the relationships between potential etiological agents and cancer based on molecular signatures. More research is needed to fully elucidate the link between heavy alcohol consumption and pancreatic cancer, and to further investigate the roles of acetaldehyde and FAEEs in pancreatic carcinogenesis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Moderate alcohol consumption and chronic disease

    DEFF Research Database (Denmark)

    Mukamal, Kenneth J; Clowry, Catherine M; Murray, Margaret M

    2016-01-01

    Drinking within recommended limits is highly prevalent in much of the world, and strong epidemiological associations exist between moderate alcohol consumption and risk of several major chronic diseases, including coronary heart disease, diabetes, and breast cancer. In many cases, plausible...... biological mediators for these associations have been identified in randomized trials, but gold standard evidence that moderate drinking causes or prevents any chronic disease remains elusive and important concerns about available evidence have been raised. Although long-term randomized trials to test...... suggests that objections to the execution of a full-scale, long-term clinical trial of moderate drinking on chronic disease are increasingly untenable. We present potential lessons learned for such a trial and discuss key features to maximize its feasibility and value....

  15. [Acute and chronic alcohol abuse and work].

    Science.gov (United States)

    Riboldi, L; Bordini, L

    2008-01-01

    A not moderate alcohol consumption or its abuse have relevant consequences not only on the health of the general population but also on the possibility to carry out any work in safety conditions. These behaviours have focused the attention of the institutions, which have promoted in the last years a growing number of preventive and informative actions and have adopted specific laws that have significantly involved the figure of occupational physician. Over the clinical implications, in fact, those behaviours, in the employment context, are associated with an increased risk of injuries (from 10 to 30% of total), an increase in the number of absences from work, with greater precariousness, with the possible interaction and/or strengthening of other occupational toxics and with the progressive reduction of working capacity. Diagnostic tools available for the detection of alcohol abuse or dependency consist, in acute cases by direct measuring of alcohol on blood, saliva and exhaled air, while in the chronic situations in addiction to the more traditional indicators (AST, ALT, GGT, MCV) there are recently introduced marker (CDT)--or in validation (ethyl glucuronide)--that representing, also with specific questionnaires (AUDIT, MAST, MALT, CAGE), useful integrated tools in the clinical-diagnostic path. The role and contribution of occupational medicine in the management of alcohol related problems is vital and relevant. Must be clear however that these are problems associated with a particular behaviour of the person and not with risks present on work-site.

  16. A comparative study of Interactions between chronic Alcohol ...

    African Journals Online (AJOL)

    Background: Variation in physiological effects of chronic alcohol consumption is attributable to interference of confounding factors like body weight, diet and sex. Objective: The aim of this study is to investigate the interactions between chronic alcohol intake, body weight, food consumption and sex in rats. Methods: The ...

  17. Acute and chronic alcohol administration: effects on performance of zebrafish in a latent learning task.

    Science.gov (United States)

    Luchiari, Ana C; Salajan, Diana C; Gerlai, Robert

    2015-04-01

    Alcohol abuse is a major medical problem. Zebrafish have been proposed to model alcohol related human disorders. Alcohol impairs learning and memory. Here, we analyze the effects of alcohol on performance of zebrafish in a recently developed latent learning paradigm. We employ a 2×3×2 experimental design (chronic×acute alcohol treatment×path blocked). The latent learning task had two phases: one, 30min long exploration trials (16 days, 1 trial/day) with left or right path of a complex maze blocked, and two, a subsequent probe trial with all paths open leading to a goal box that now contained stimulus fish. During the 16 days each fish received one of two chronic treatments: freshwater or 0.50% (v/v%) alcohol. Subsequently, fish were immersed for 1h in one of the following solutions: 0.00 (freshwater), 0.50% or 1.00% alcohol, the acute challenge. Behavior of fish was recorded during the probe trial that commenced immediately after the acute treatment. Path choices, latency to leave the start box and to enter the goal box, time spent in the goal box, distance traveled, and duration of freezing were quantified. We found that acute exposure to 1.00% alcohol after chronic freshwater disrupted learning performance, so did exposure to freshwater after chronic alcohol treatment (withdrawal). We also found exposure to chronic alcohol to diminish the effect of subsequent acute alcohol suggesting development of tolerance. Our results demonstrate that analysis of learning performance of zebrafish allows detection of alcohol-induced functional changes. The simplicity and scalability of the employed task also imply the utility of the zebrafish in high throughput drug screens. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Chronic alcoholism-mediated metabolic disorders in albino rat testes

    OpenAIRE

    Shayakhmetova Ganna M.; Bondarenko Larysa B.; Matvienko Anatoliy V.; Kovalenko Valentina M.

    2014-01-01

    There is good evidence for impairment of spermatogenesis and reductions in sperm counts and testosterone levels in chronic alcoholics. The mechanisms for these effects have not yet been studied in detail. The consequences of chronic alcohol consumption on the structure and/or metabolism of testis cell macromolecules require to be intensively investigated. The present work reports the effects of chronic alcoholism on contents of free amino acids, levels of cytochrome P450 3A2 (CYP3A2) mRNA exp...

  19. Beta-carbolines in chronic alcoholics following trauma.

    Science.gov (United States)

    Spies, C D; Rommelspacher, H; Winkler, T; Müller, C; Brummer, G; Funk, T; Berger, G; Fell, M; Blum, S; Specht, M; Hannemann, L; Schaffartzik, W

    1996-01-01

    In our society every second polytraumatized patient is a chronic alcoholic. A patient's alcohol-related history is often unavailable and laboratory markers are not sensitive or specific enough to detect alcohol-dependent patients who are at risk of developing alcohol withdrawal syndrome (AWS) during their post-traumatic intensive care unit (ICU) stay. Previously, it has been found that plasma levels of norharman are elevated in chronic alcoholics. We investigated whether beta-carbolines, i.e. harman and norharman levels, could identify chronic alcoholics following trauma and whether possible changes during ICU stay could serve as a predictor of deterioration of clinical status. Sixty polytraumatized patients were transferred to the ICU following admission to the emergency room and subsequent surgery. Chronic alcoholics were included only if they met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use and their daily ethanol intake was > or =60 g. Harman and norharman levels were assayed on admission and on days 2, 4, 7 and 14 in the ICU. Harman and norharman levels were determined by high pressure liquid chromatography. Elevated norharman levels were found in chronic alcoholics (n = 35) on admission to the hospital and remained significantly elevated during their ICU stay. The area under the curves (AUC) showed that norharman was comparable to carbohydrate-deficient transferrin (CDT) and superior to conventional laboratory markers in detecting chronic alcoholics. Seventeen chronic alcoholics developed AWS; 16 of these patients experienced hallucinations or delirium. Norharman levels were significantly increased on days 2 and 4 in the ICU in patients who developed AWS compared with those who did not. An increase in norharman levels preceded hallucinations or delirium with a median period of approximately 3 days. The findings that elevated norharman levels are found in chronic alcoholics, that the AUC was in the range of CDT

  20. [Nutritional care of elderly people with chronic alcoholism].

    Science.gov (United States)

    Brugerolles, Héléna; Mathy, Fabrice; Emery, Sophie; Hervé, Christian

    2014-01-01

    The management of elderly people with chronic alcoholism involves several players, including dieticians.Without stigmatisingthe person or apportioning blame, the challenge is to enable them to become a player in their treatment. Long-term support is required.

  1. Alcoholic chronic pancreatitis: A quality of life study

    OpenAIRE

    Simone Carla BENINCÁ; Angelica de Freitas MELHEM; Renato Duffles MARTINS; Ermelindo Della LIBERA JÚNIOR

    2016-01-01

    ABSTRACT Objective: To compare the quality of life between patients with alcoholic chronic pancreatitis and controls, and between diabetic and non-diabetic patients, correlating clinical, sociodemographic, and nutritional factors with their quality of life scores. Methods: Forty-three outpatients of the pancreas and biliary tract clinic diagnosed with alcoholic chronic pancreatitis were assessed. Quality of life was measured by the Brazilian version of the Short Form-36. The control group c...

  2. Menstrual disturbances and fertility in chronic alcoholic women

    DEFF Research Database (Denmark)

    Becker, U; Tønnesen, H; Kaas-Claesson, N

    1989-01-01

    Data on menstrual pattern, gynecological disorders and infertility were obtained from 51 chronic alcoholic women aged 20--42 years attending an outpatient clinic for alcoholics, using 51 randomly drawn age-matched healthy women as controls. A higher variability (P less than 0.05) in the duration ...

  3. Genetic polymorphisms in alcohol-metabolizing enzymes and chronic pancreatitis.

    NARCIS (Netherlands)

    Verlaan, M.; Morsche, R.H.M. te; Roelofs, H.M.J.; Laheij, R.J.F.; Jansen, J.B.M.J.; Peters, W.H.M.; Drenth, J.P.H.

    2004-01-01

    AIMS: Alcohol misuse is now regarded as an important risk factor for development of chronic pancreatitis (CP). However, not every alcohol misuser develops CP and it therefore might be suggested that susceptibility could be further influenced by inter-individual variations in the activities of

  4. Recent developments in the treatment of alcoholic chronic pancreatitis.

    Science.gov (United States)

    Tsujimoto, Tatsuhiro; Kawaratani, Hideto; Yoshiji, Hitoshi; Uemura, Masahito; Fukui, Hiroshi

    2008-06-01

    Chronic pancreatitis is a progressive inflammatory condition characterized by repeated attacks of abdominal pain, and the destruction and fibrosis of the pancreatic parenchyma which causes to reduced exocrine and endocrine functions. Alcohol is the most common cause of chronic pancreatitis. Although abstinence is usually considered a prerequisite for successful treatment of alcoholic chronic pancreatitis, we often encounter patients who have repeated attacks from the compensated stage through the transitional stage. In alcoholic chronic pancreatitis, continued alcohol consumption causes changes in the digestive hormones and vagal nerve function that induce the pancreatic acinar cells to oversecrete protein, increasing the protein concentration and viscosity of the pancreatic juice. This induces protein sedimentation from the pancreatic juice and formation of protein plugs within the pancreatic duct, triggering repeated attacks of acute pancreatitis. The treatment of alcoholic chronic pancreatitis includes alleviation of symptoms, particularly abdominal pain, elimination of trigger factors, prevention of recurrence and disease progression, adjuvant therapies for pancreatic exocrine and endocrine failure. Recently, the main constituent proteins in these protein plugs have been identified, enabling trials of several therapies, such as the administration of secretin formulations and endoscopic removal. Bromhexine hydrochloride, a bronchial mucolytic, has an affinity for the pancreatic acinar cells, inducing them to secrete pancreatic juice of low viscosity. In this review, we summarize the most recent thoughts about alcoholic chronic pancreatitis, and the new treatments, and in particular, we present our findings concerning the efficacy of bromhexine hydrochloride in the treatment of this disease.

  5. The effect of alcohol advertising on immediate alcohol consumption in college students: an experimental study.

    Science.gov (United States)

    Koordeman, Renske; Anschutz, Doeschka J; Engels, Rutger C M E

    2012-05-01

    Survey studies have emphasized a positive association between exposure to alcohol advertising on television (TV) and the onset and continuation of drinking among young people. Alcohol advertising might also directly influence viewers' consumption of alcohol while watching TV. The present study therefore tested the immediate effects of alcohol advertisements on the alcohol consumption of young adults while watching a movie. Weekly drinking, problem drinking, positive and arousal expectancies of alcohol, ad recall, attitude, and skepticism toward the ads were tested as moderators. An experimental design comparing 2 advertisement conditions (alcohol ads vs. nonalcohol ads) was used. A total of 80 men, young adult friendly dyads (ages 18 to 29) participated. The study examined actual alcohol consumption while watching a 1-hour movie with 3 advertising breaks. A multivariate regression analysis was used to examine the effects of advertisement condition on alcohol consumption. Assignment to the alcohol advertisement condition did not increase alcohol consumption. In addition, no moderating effects between advertisement condition and the individual factors on alcohol consumption were found. Viewing alcohol advertising did not lead to higher alcohol consumption in young men while watching a movie. However, replications of this study using other samples (e.g., different countries and cultures), other settings (e.g., movie theater, home), and with other designs (e.g., different movies and alcohol ads, cumulative exposure, extended exposure effects) are warranted. Copyright © 2011 by the Research Society on Alcoholism.

  6. Characteristics of benzodiazepine receptors in rats differing in predisposition to experimental alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Burov, Yu.V.; Maiskii, A.I.; Yukhananov, R.Yu.

    1986-02-01

    This paper studies the number and affinity of benzodiazepine receptors for diazepam in the cerebral cortex and hippocampus of rats differently predisposed to the development of experimental alcoholism. Ethanol was injected once intraperitoneally, in a dose of 2.5 g/kg. Control animals received the same volume of physiological saline. Bound and free N-methyl-tritium-diazepam were separated by means of GF/B filters. The characteristics of benzodiazepine receptors are shown in rats differing in predisposition to the development of experimental alcoholism and in rats during voluntary chronic alcoholization. It is shown that weakening of functional acitivity of the GABA-benzodiazepam complex in animals predisposed to the development of experimental alcoholism is one of the neurochemical mechanisms of development of the abstinence syndrome.

  7. Effects of alcohol portrayals in movies on actual alcohol consumption: an observational experimental study

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; van Baaren, R.B.; Engels, R.C.M.E.

    2011-01-01

    Aims This study uses an experimental design to assess the effects of movie alcohol portrayal on alcohol consumption of young adults while watching a movie. Gender, weekly alcohol use and identification with the movie actor/character were assessed as moderators. Design A two (sex) × two (movie:

  8. Effects of alcohol portrayals in movies on actual alcohol consumption: an observational experimental study

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Baaren, R.B. van; Engels, R.C.M.E.

    2011-01-01

    Aims - This study uses an experimental design to assess the effects of movie alcohol portrayal on alcohol consumption of young adults while watching a movie. Gender, weekly alcohol use and identification with the movie actor/character were assessed as moderators. Design - A two (sex) x two (movie:

  9. Effects of alcohol portrayals in movies on actual alcohol consumption: An observational experimental study

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Baaren, R.B. van; Engels, R.C.M.E.

    2011-01-01

    Aims - This study uses an experimental design to assess the effects of movie alcohol portrayal on alcohol consumption of young adults while watching a movie. Gender, weekly alcohol use and identification with the movie actor/character were assessed as moderators. Design - A two (sex) x two (movie:

  10. Water metabolism in rats subjected to chronic alcohol administration

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Pohl, C.; Bode, J.C.

    2004-01-01

    and certain renal functions in rats during a period of 12 months. ANIMALS AND STUDY DESIGN: Male Wistar rats received either alcohol (15% v/v; group A, n = 65) or tap water (group C, n = 35) as drinking fluid. Urine and faeces were collected from 6 rats of each group during 7 days, at monthly intervals...... the body as hidden water loss increases after alcohol consumption by up to 25-26% over control values.......AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion...

  11. Effect of Chronic Alcohol Consumption on Phosphatidylcholine ...

    African Journals Online (AJOL)

    as a new marker for alcohol-induced oxidative stress. The positive correlation between PC-OOH content and other oxidative index in both of the liver and brain has demonstrated that PC-OOH content in the tissue as a new marker for alcohol- induced oxidative stress. Since the method of determination PC-OOH has.

  12. Multifocal Osteonecrosis Secondary to Chronic Alcohol Ingestion

    Directory of Open Access Journals (Sweden)

    Kazu Matsumoto

    2015-01-01

    Full Text Available Multifocal osteonecrosis is a relatively rare disorder with an estimated incidence of around 3% among patients diagnosed as having osteonecrosis. Multifocal osteonecrosis is caused by the several conditions including corticosteroid treatment, coagulation disorders, connective tissue disorders including systemic lupus erythematosus (SLE, inflammatory bowel disease, renal transplantation, and underlying malignancies. Alcohol abuse is one of the risk factors for osteonecrosis, and alcohol-induced osteonecrosis is 5% among all the osteonecrosis. Furthermore, the overall incidence of alcohol-induced multifocal osteonecrosis was approximately 6% among all the osteonecrosis induced by the alcohol. Therefore, here, we report an extremely rare case of alcohol-induced multifocal osteonecrosis involving three joints (two knees and one hip and review the related literature.

  13. Chronic alcoholism-mediated metabolic disorders in albino rat testes.

    Science.gov (United States)

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Matvienko, Anatoliy V; Kovalenko, Valentina M

    2014-09-01

    There is good evidence for impairment of spermatogenesis and reductions in sperm counts and testosterone levels in chronic alcoholics. The mechanisms for these effects have not yet been studied in detail. The consequences of chronic alcohol consumption on the structure and/or metabolism of testis cell macromolecules require to be intensively investigated. The present work reports the effects of chronic alcoholism on contents of free amino acids, levels of cytochrome P450 3A2 (CYP3A2) mRNA expression and DNA fragmentation, as well as on contents of different cholesterol fractions and protein thiol groups in rat testes. Wistar albino male rats were divided into two groups: I - control (intact animals), II - chronic alcoholism (15% ethanol self-administration during 150 days). Following 150 days of alcohol consumption, testicular free amino acid content was found to be significantly changed as compared with control. The most profound changes were registered for contents of lysine (-53%) and methionine (+133%). The intensity of DNA fragmentation in alcohol-treated rat testes was considerably increased, on the contrary CYP3A2 mRNA expression in testis cells was inhibited, testicular contents of total and etherified cholesterol increased by 25% and 45% respectively, and protein SH-groups decreased by 13%. Multidirectional changes of the activities of testicular dehydrogenases were detected. We thus obtained complex assessment of chronic alcoholism effects in male gonads, affecting especially amino acid, protein, ATP and NADPH metabolism. Our results demonstrated profound changes in testes on the level of proteome and genome. We suggest that the revealed metabolic disorders can have negative implication on cellular regulation of spermatogenesis under long-term ethanol exposure.

  14. Alcoholic chronic pancreatitis: A quality of life study

    Directory of Open Access Journals (Sweden)

    Simone Carla BENINCÁ

    2016-02-01

    Full Text Available ABSTRACT Objective: To compare the quality of life between patients with alcoholic chronic pancreatitis and controls, and between diabetic and non-diabetic patients, correlating clinical, sociodemographic, and nutritional factors with their quality of life scores. Methods: Forty-three outpatients of the pancreas and biliary tract clinic diagnosed with alcoholic chronic pancreatitis were assessed. Quality of life was measured by the Brazilian version of the Short Form-36. The control group consisted of 43 healthy companions. Nutritional status was classified according to body mass index and triceps, biceps, suprailiac, and subscapular skinfold thicknesses, using the appropriate methods. The percentage of body fat was given by adding the four skinfold thicknesses and by bioelectrical impedance analysis. The statistical tests included the Chi-square, Mann-Whitney, and Spearman's correlation tests, with the significance level set at p<0.05. Results: The sociodemographic variables of the case and control groups did not differ. Quality of life was lower in alcoholic chronic pancreatitis patients than in controls. The only quality of life domain that differed between diabetics and non-diabetics was functional capacity, lower in diabetics (p=0.022. Smoking duration, alcohol intake in grams, and time since pancreatic surgery correlated negatively with the quality of life of alcoholic chronic pancreatitis patients. Old age, skinfold thicknesses, and percentage of body fat correlated positively with quality of life. Conclusion: Quality of life is low in alcoholic chronic pancreatitis patients because of the negative influence of certain factors, such as smoking duration, amount of alcohol consumed, and time since pancreatic surgery.

  15. Chronic alcoholism-mediated metabolic disorders in albino rat testes

    Directory of Open Access Journals (Sweden)

    Shayakhmetova Ganna M.

    2014-09-01

    Full Text Available There is good evidence for impairment of spermatogenesis and reductions in sperm counts and testosterone levels in chronic alcoholics. The mechanisms for these effects have not yet been studied in detail. The consequences of chronic alcohol consumption on the structure and/or metabolism of testis cell macromolecules require to be intensively investigated. The present work reports the effects of chronic alcoholism on contents of free amino acids, levels of cytochrome P450 3A2 (CYP3A2 mRNA expression and DNA fragmentation, as well as on contents of different cholesterol fractions and protein thiol groups in rat testes. Wistar albino male rats were divided into two groups: I - control (intact animals, II - chronic alcoholism (15% ethanol self-administration during 150 days. Following 150 days of alcohol consumption, testicular free amino acid content was found to be significantly changed as compared with control. The most profound changes were registered for contents of lysine (-53% and methionine (+133%. The intensity of DNA fragmentation in alcohol-treated rat testes was considerably increased, on the contrary CYP3A2 mRNA expression in testis cells was inhibited, testicular contents of total and etherified cholesterol increased by 25% and 45% respectively, and protein SH-groups decreased by 13%. Multidirectional changes of the activities of testicular dehydrogenases were detected. We thus obtained complex assessment of chronic alcoholism effects in male gonads, affecting especially amino acid, protein, ATP and NADPH metabolism. Our results demonstrated profound changes in testes on the level of proteome and genome. We suggest that the revealed metabolic disorders can have negative implication on cellular regulation of spermatogenesis under long-term ethanol exposure.

  16. Comorbidities, confounders, and the white matter transcriptome in chronic alcoholism.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Sheahan, Pam J; Kaplan, Warren; Kril, Jillian J

    2014-04-01

    Alcohol abuse is the world's third leading cause of disease and disability, and one potential sequel of chronic abuse is alcohol-related brain damage (ARBD). This clinically manifests as cognitive dysfunction and pathologically as atrophy of white matter (WM) in particular. The mechanism linking chronic alcohol intoxication with ARBD remains largely unknown but it is also complicated by common comorbidities such as liver damage and nutritional deficiencies. Liver cirrhosis, in particular, often leads to hepatic encephalopathy (HE), a primary glial disease. In a novel transcriptomic study, we targeted the WM only of chronic alcoholics in an attempt to tease apart the pathogenesis of ARBD. Specifically, in alcoholics with and without HE, we explored both the prefrontal and primary motor cortices, 2 regions that experience differential levels of neuronal loss. Our results suggest that HE, along with 2 confounders, gray matter contamination, and low RNA quality are major drivers of gene expression in ARBD. All 3 exceeded the effects of alcohol itself. In particular, low-quality RNA samples were characterized by an up-regulation of translation machinery, while HE was associated with a down-regulation of mitochondrial energy metabolism pathways. The findings in HE alcoholics are consistent with the metabolic acidosis seen in this condition. In contrast non-HE alcoholics had widespread but only subtle changes in gene expression in their WM. Notwithstanding the latter result, this study demonstrates that significant confounders in transcriptomic studies of human postmortem brain tissue can be identified, quantified, and "removed" to reveal disease-specific signals. Copyright © 2014 by the Research Society on Alcoholism.

  17. [Alcoholism as chronic disease: a challenge for the physician].

    Science.gov (United States)

    Kruse, G

    1996-10-20

    Alcoholism is associated with a high relapse rate; within four years of a successful intensive hospital withdrawal program a good 50 percent of the patients have relapsed again. In view of this result of research into alcoholism an "aims hierarchy" has been established which meets the requirements of relapsed alcoholics while expressly rejecting the limitation of therapeutic measures to the purely somatic. Psychotherapeutic considerations that take account of the specific situation of the chronic, often multimorbid patient are applied already in the early phase of treatment. For example, relapse must not be interpreted as a failure of previous treatments or even be used as an excuse to abandon therapy.

  18. Effect of Chronic Alcohol Consumption on Phosphatidylcholine ...

    African Journals Online (AJOL)

    Purpose: To investigate the correlation between alcohol-induced oxidative stress and tissue phosphatidylcholine hydroperoxide (PC-OOH) content of rat liver and brain. Methods: Ten Wistar rats were divided into two groups: one group was given 20 % ethanol (5 g/kg) and the other the same volume of normal saline, orally ...

  19. Chronic Alcohol Ingestion Changes the Landscape of the Alveolar Epithelium

    Directory of Open Access Journals (Sweden)

    Charles A. Downs

    2013-01-01

    Full Text Available Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC. The cascading effect of tissue and phagocytic Nadph oxidase (Nox may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS for which hospitalized alcoholics are at an increased risk.

  20. Alcohol Consumption and Viral Hepatitis in Chronic Liver Disease in ...

    African Journals Online (AJOL)

    Background: Precise assessment of the risks and interactions of alcohol consumption and viral hepatitis in the aetiology of chronic liver disease [CLD] are not locally available. Methodology: 74 patients with CLD and 74 controls were evaluated for Hepatitis B and C infection [anti-HCV, HBsAg]. The type and amount of ...

  1. Compensatory recruitment of neural resources in chronic alcoholism.

    Science.gov (United States)

    Chanraud, Sandra; Sullivan, Edith V

    2014-01-01

    Functional recovery occurs with sustained sobriety, but the neural mechanisms enabling recovery are only now emerging. Theories about promising mechanisms involve concepts of neuroadaptation, where excessive alcohol consumption results in untoward structural and functional brain changes which are subsequently candidates for reversal with sobriety. Views on functional adaptation in chronic alcoholism have expanded with results from neuroimaging studies. Here, we first describe and define the concept of neuroadaptation according to emerging theories based on the growing literature in aging-related cognitive functioning. Then we describe findings as they apply to chronic alcoholism and factors that could influence compensation, such as functional brain reserve and the integrity of brain structure. Finally, we review brain plasticity based on physiologic mechanisms that could underlie mechanisms of neural compensation. Where possible, we provide operational criteria to define functional and neural compensation. © 2014 Elsevier B.V. All rights reserved.

  2. An Atypical Presentation of Subacute Encephalopathy with Seizures in Chronic Alcoholism Syndrome

    OpenAIRE

    Kim, Tae-Kyoung; Jung, Eui Sung; Park, Jong-Moo; Kang, Kyusik; Lee, Woong-Woo; Lee, Jung-Ju

    2016-01-01

    Subacute encephalopathy with seizures in chronic alcoholism syndrome is a rare clinical manifestation in patients with chronic alcohol abuse. We report the case of a patient with chronic alcoholism who presented with partial nonconvulsive status epilepticus associated with a thalamic lesion.

  3. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  4. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research.

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Crespo Yanguas, Sara; Colle, Isabelle; Van Den Bossche, Bert; Da Silva, Tereza Cristina; de Oliveira, Cláudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini; Cogliati, Bruno; Vinken, Mathieu

    2015-07-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and '-omics'-based read-outs are still in their infancy, but show great promise. In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Plasma carnitine concentrations after chronic alcohol intoxication 

    Directory of Open Access Journals (Sweden)

    Alina Kępka

    2013-05-01

    Full Text Available Background: Carnitine transports fatty acids from the cytoplasm to the mitochondrial matrix, where the fatty acids are oxidized. Chronic alcohol consumption reduces the concentration of carnitine and interferes with oxidative processes occurring in the cell.Aim: The assessment of carnitine concentrations in plasma of chronically intoxicated alcohol dependent persons in a 49-day abstinence period.Material/Methods: The study included 31 patients (5 women and 27 men aged from 26 to 60 years (44.6± 8.9 and 32 healthy subjects (15 women and 17 men aged 22-60 years (39.8± 9.4. The patients’ alcohol dependence ranged from 2 to 30 years (13.6± 7.5. Examined subjects consumed 75-700 g of ethanol/day (226.9± 151.5. Plasma concentrations of free and total carnitine were measured three times: at the first (T0, 30th (T30 and 49th (T49 day of hospital detoxification. Free (FC and total (TC carnitine were determined by the spectrophotometric method. Plasma acylcarnitine (AC concentration was calculated from the difference between TC and FC; then the AC/FC ratio was calculated. To determine statistically significant differences for related variables, Student’s t-test was used.Results: At T0, alcoholics had significantly lower concentration of FC and TC (p < 0.05 in plasma, as compared to the control group. In comparison to controls, at T30, plasma TC and FC (p < 0.01 as well as AC (p < 0.001 were reduced. The lowest concentration of TC, FC and AC (p < 0.001was found at T49. The ratio of AC/FC at T0 had a tendency to be higher in alcoholics than in the control group (p = 0.05, whereas at T49 it was significantly lower in alcoholics as compared to the control subjects (p < 0.05.Conclusions: Chronic alcohol intoxication causes a plasma deficiency of carnitine. Forty-nine days of abstinence showed a significant decrease in the concentration of TC, FC and AC. Further research is necessary to clarify whether a low level of plasma carnitine

  6. Multiparameter rodent chronic model for complex evaluation of alcoholism-mediated metabolic violations.

    Science.gov (United States)

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Kovalenko, Valentina M; Kharchenko, Olga I; Bohun, Larisa I; Omelchenko, Yuliya O

    2015-01-01

    Despite of the wide spectrum of alcoholism experimental models, the majority of them are very specialized on the short list of investigated parameters and could not provide reproduction of complex metabolic changes in the rats. The aim of the present study was to estimate whether rats selected by high alcohol preference, allowed free access to 15% alcohol for 150 days, develop simultaneous multilevel disturbances of cell macromolecules structure, metabolism and oxidative/nitrosative stress. Wistar albino male rats were divided into groups: I - rats selected by preferences to alcohol were used for chronic alcoholism modeling by replacing water with 15% ethanol (150 days), II - control. Contents of amino acids in serum, liver mRNA CYP2E1 and CYP3A2 expression, DNA fragmentation and lipid peroxidation levels, the reduced glutathione content, superoxide dismutase, catalase, iNOS and cNOS activities were evaluated. In serum of ethanol-treated rats contents of aspartic acid, serine, glycine, alanine and valine were decreased whereas contents of histidine, methionine and phenylalanine were increased. Liver CYP2E1, CYP3A2 mRNA expression, DNA fragmentation levels significantly elevated. Level of cNOS in ethanol-treated rat's hepatocytes was within the normal limits, whereas iNOS activity was raised 1.6 times. Liver pro- and anti-oxidant system alterations were shown. Rats' chronic 15% alcohol consumption (150 days) led solely to complex metabolomic changes at different levels, which simultaneously characterized cell macromolecules structure, metabolism, and oxidative/nitrosative stress. Rodent model of chronic alcoholism in the proposed modification could be an adequate and reasonably priced tool for further preclinical development and testing of pharmacotherapeutic agents.

  7. Intercurrent complications in chronic alcoholic men admitted to the intensive care unit following trauma.

    Science.gov (United States)

    Spies, C D; Neuner, B; Neumann, T; Blum, S; Müller, C; Rommelspacher, H; Rieger, A; Sanft, C; Specht, M; Hannemann, L; Striebel, H W; Schaffartzik, W

    1996-04-01

    A chronic alcoholic group following trauma was investigated to determine whether their ICU stay was longer than that of a non-alcoholic group and whether their intercurrent complication rate was increased. Prospective study. An intensive care unit. A total of 102 polytraumatized patients were transferred to the ICU after admission to the emergency room and after surgical treatment. Of these patients 69 were chronic alcoholics and 33 were allocated to the non-alcoholic group. The chronic-alcoholic group. met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in these patients was > or = 60 g. Diagnostic indicators included an alcoholism-related questionnaire (CAGE), conventional laboratory markers and carbohydrate-deficient transferrin. Major intercurrent complications such as alcohol withdrawal syndrome (AWS), pneumonia, cardiac complications and bleeding disorders were documented and defined according to internationally accepted criteria. Patients did not differ significantly between groups regarding age, TRISS and APACHE score on admission. The rate of major intercurrent complications was 196% in the chronic alcoholic vs 70% in the non-alcoholic group (p = 0.0001). Because of the increased intercurrent complication rate, the ICU stay was significantly prolonged in the chronic-alcoholic group by a median period of 9 days. Chronic alcoholics are reported to have an increased risk of morbidity and mortality. However, to our knowledge, nothing is known about the morbidity and mortality of chronic alcoholics in intensive care units following trauma. Since chronic alcoholics in the ICU develop more major complications with a significantly prolonged ICU stay following trauma than non-alcoholics, it seems reasonable to intensify research to identify chronic alcoholics and to prevent alcohol-related complications.

  8. Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim; Poulsen, Henrik Enghusen

    2002-01-01

    The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were...... studied, giving special attention to alcohol history, time between overdose and intravenous N-acetylcysteine (NAC) treatment ("time to NAC"), and other data available at the time of admittance. Up until 72 hours after ingestion, time to NAC was the single most important independent risk factor....... With a time to NAC less than 12 hours, the mortality rate was 0.42% (95% CI, 0.05-2.7). When time to NAC exceeded 12, 24, and 48 hours, the mortality rate increased to 6.1%, 13%, and 19%, respectively. Chronic alcohol abuse was an independent risk factor of mortality (odds ratio [OR], 3.52; 95% CI, 1...

  9. [Morphological signs of ethanol poisoning, alcohol abstinence and chronic alcoholic intoxication in the mesocorticolimbic dopaminergic system].

    Science.gov (United States)

    Droblenkov, A V

    2011-01-01

    Forensic medical diagnostics of ethanol poisoning, alcohol abstinence, and chronic alcoholic intoxication of the mesocorticolimbic dopaminergic system remains an unresolved problem and encounters difficulties. This situation is due not only to the marked vulnerability of the neurons of the dopaminergic system but also to the fact that its mechanisms are poorly understood. The objective of the present work was to substantiate and develop diagnostic criteria for ethanol poisoning, alcohol abstinence, and chronic alcoholic intoxication of the neurons both in the mesocorticolimbic dopaminergic system and in other brain regions. The object of the study was the brain of healthy adult subjects who died from alcohol intoxication (in the period of ethanol resorption) and under conditions of alcohol abstinence (completion of the abstinence course). The purpose of the study was to elucidate factors responsible for the different degree of damage to the neurons of various identification groups (intact, hypochromic, picnomorphic, shadow) and macrogliocytes. The cells of all these types were counted at an area of 0.25 sq. mm within 4 squares each having a side of 250 mcm in length. The absolute and relative number of neurons in each group as well as the number of polyneuronal satellite cells per one intact neuron was determined. It was shown that alcohol intoxication is associated with acute swelling of and severe damage to brain neurons caused by the combination of such factors as toxic effect of ethanol, excessive production of catecholamines, and functional overstrain of dopaminergic neurons. The severity of acute alcohol damage to the neurons decreased with the distance from the mid-brain dopaminergic nuclei. Restoration of neurons during alcohol abstinence was due to compensatory activation of interactions between neurons and glial cells. It decreased in the sequence from the paranigral nucleus of the ventral portion of mesencephalic tegumentum to the medial portion of the

  10. Effects of alcohol and frustration on experimental graffiti.

    Science.gov (United States)

    Norlander, T; Nordmarker, A; Archer, T

    1998-12-01

    This study aimed to examine effects between alcohol and frustration in regard to graffiti. Forty-two subjects, 21 men and 21 women were randomly assigned in equal numbers to each of the three experimental groups, namely a Control group, an Alcohol group, and an Alcohol + Frustration group (alcohol dose: 1 ml 100% alcohol/kg body weight). For the purposes of this experiment, a test (AET) was constructed that provided scores of "scrawling-graffiti" (i.e., the amount of scrawling on pictures), "destruction", "aggression", and "sexuality". An elaboration test and a test measuring the "dispositional optimism" were also applied. The primary results indicated that (a) the Alcohol + Frustration group scored significantly higher on scrawling-graffiti compared to the Control group, (b) female subjects performed graffiti-scrawling to a greater extent than male subjects in all three groups, (c) women scored significantly higher on elaboration as compared to men. These results were interpreted as supporting the hypothesis that alcohol intake by itself is unlikely to induce destructive behavior unless accompanied by a "provocative" factor (e.g. frustration) that precipitates the putative expressions of aggressiveness.

  11. Peculiarities of death and regeneration of pancreas cells at early stages of alcoholic chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    N. Y. Oshmyanska

    2014-10-01

    Full Text Available The study has been conducted on 39 white laboratory male rats which formed 5 groups: experimental occlusal pancreatitis caused by ligation of the main pancreatic duct (n = 6, experimental alcoholic pancreatitis caused by oral intake of alcohol (n = 6, against the background of an excess (n = 6 or deficiency (n = 6 of nitric oxide, as well as a control group (n = 15. This study provides the detailed description of the processes of death and regeneration in the islets of Langerhans, typical for early stages of the disease. The expression of the proliferation markers (PCNA and Neurogenin-3 has been analyzed using histological and immunohistochemical methods along with the changes of morphological structure, that led to initiation of the alcoholic chronic pancreatitis against the background of imbalance in NO-ergic regulatory system caused by an excess or deficiency of nitric oxide. It has been found that ligation of the pancreatic duct in the experiment reconstructedthe circumstances of chronic pancreatitis in rats and caused the activation of fibrosis and regeneration of endocrine and exocrine tissue. Compared with occlusion, the effects of ethanol on the pancreas also manifested in the activation of fibrogenesis, but the structural changes were negligible and could unlikely lead to advanced fibrosis and chronic pancreatitis in the future. On the other side, an imbalance of NO-system in alcoholic rats leads to disruption of the zymogens secretion in the acinar cells and dilatation of the capillary network in islets. Uneven distribution of zymogen granules may lead to their intracellular activation as evidenced by the deformation of acini and focal apoptosis without inflammatory response. In this case, violation of the key adaptive responses in the pancreas makes it more vulnerable to the effects of ethanol, its metabolites, and other environmental factors, and may increase the probability of chronic pancreatitis development. At the same time

  12. The effect of chronic alcohol intoxication and smoking on the activity of oral peroxidase The effect of chronic alcohol intoxication and smoking on the activity of oral peroxidase

    Directory of Open Access Journals (Sweden)

    Napoleon Waszkiewicz

    2012-10-01

    Full Text Available Peroxidase is the most important antioxidant enzyme in saliva. Through peroxidation of thiocyanate in
    the presence of H2O2, peroxidase catalyses the formation of bacteriocidic compounds such as hypothiocyanate.
    The purpose of this study was to evaluate the effect of chronic alcohol intoxication and smoking on the activity
    of oral peroxidase (OPO. A total of 37 volunteers participated in the study. This cohort consisted of 17 male
    alcohol-dependent smoking patients after chronic alcohol intoxication (AS group, alcohol + smoking (mean
    age: 42 years; range: 26–55 (100–700 g/day of alcohol; 10–20 cigarettes/day and 20 control male social drinkers
    (CNS group, control non-smokers with no history of alcohol abuse or smoking (mean age: 42 years; range:
    30–53. Salivary peroxidase activity was measured by the colorimetric method. The differences between groups
    were evaluated using the Mann–Whitney U test. There was significantly higher activity of OPO (p = 0.00001
    and significantly lower salivary flow (SF (p = 0.007 in alcohol-dependent smokers after chronic alcohol intoxication
    compared to the control group. OPO activity significantly correlated with the number of days of alcohol
    intoxication, but not with smoking. Gingival index (GI was significantly higher in smoking alcohol-dependent
    persons than in the control group, and correlated with OPO activity. The sensitivity of the OPO test was 70% in
    smoking alcoholics, while specificity was 95%. The increased activity of OPO suggests chronic oxidative stress is
    more likely due to ethanol action than to smoking. Smoking alcohol-dependent persons have a worse periodontal
    status than controls. OPO activity as a marker of chronic alcohol abuse may help in the diagnosis of alcoholism.Peroxidase is the most important antioxidant enzyme in saliva. Through peroxidation of thiocyanate in
    the presence of H2O2, peroxidase

  13. Chronic alcohol ingestion exacerbates skeletal muscle myopathy in HIV-1 transgenic rats

    Directory of Open Access Journals (Sweden)

    Bratina Margaux A

    2011-08-01

    Full Text Available Abstract Background Separately, chronic alcohol ingestion and HIV-1 infection are associated with severe skeletal muscle derangements, including atrophy and wasting, weakness, and fatigue. One prospective cohort study reported that 41% of HIV-infected patients met the criteria for alcoholism, however; few reports exist on the co-morbid effects of these two disease processes on skeletal muscle homeostasis. Thus, we analyzed the atrophic effects of chronic alcohol ingestion in HIV-1 transgenic rats and identified alterations to several catabolic and anabolic factors. Findings Relative plantaris mass, total protein content, and fiber cross-sectional area were reduced in each experimental group compared to healthy, control-fed rats. Alcohol abuse further reduced plantaris fiber area in HIV-1 transgenic rats. Consistent with previous reports, gene levels of myostatin and its receptor activin IIB were not increased in HIV-1 transgenic rat muscle. However, myostatin and activin IIB were induced in healthy and HIV-1 transgenic rats fed alcohol for 12 weeks. Catabolic signaling factors such as TGFβ1, TNFα, and phospho-p38/total-p38 were increased in all groups compared to controls. There was no effect on IL-6, leukemia inhibitory factor (LIF, cardiotrophin-1 (CT-1, or ciliary neurotrophic factor (CNTF in control-fed, transgenic rats. However, the co-morbidity of chronic alcohol abuse and HIV-1-related protein expression decreased expression of the two anabolic factors, CT-1 and CNTF. Conclusions Consistent with previous reports, alcohol abuse accentuated skeletal muscle atrophy in an animal model of HIV/AIDS. While some catabolic pathways known to drive alcoholic or HIV-1-associated myopathies were also elevated in this co-morbid model (e.g., TGFβ1, consistent expression patterns were not apparent. Thus, specific alterations to signaling mechanisms such as the induction of the myostatin/activin IIB system or reductions in growth factor signaling via

  14. Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST

    Science.gov (United States)

    Alterations in hypothalamic–pituitary–adrenal axis function contribute to many of the adverse behavioral effects of chronic voluntary alcohol drinking, including alcohol dependence and mood disorders; limbic brain structures such as the bed nucleus of the stria termin...

  15. Reversible loss of reproductive fitness in zebrafish on chronic alcohol exposure.

    Science.gov (United States)

    Dewari, Pooran Singh; Ajani, Funmilola; Kushawah, Gopal; Kumar, Damera Santhosh; Mishra, Rakesh K

    2016-02-01

    Alcoholism is one of the most prevalent diseases in society and causes significant health and social problems. Alcohol consumption by pregnant women is reported to cause adverse effects on the physical and psychological growth of the fetus. However, the direct effect of chronic alcohol consumption on reproductive fitness has not been tested. In recent years, the zebrafish (Danio rerio) has emerged as a versatile model system to study the effects of alcohol on behavior and embryonic development. We utilized the zebrafish model system to address the effect of chronic alcohol exposure (0.5% alcohol in the holding tank for 9 weeks) on reproductive capacity. We found a dramatic decrease in fecundity, measured by counting the number of eggs laid, when at least one of the parents is subject to chronic alcohol exposure. Interestingly, a 9-week alcohol withdrawal program completely restored the reproductive capacity of the treated subjects. In agreement with observations on fecundity, the chronic alcohol exposure leads to increased anxiety, as measured by the novel-tank diving assay. Conversely, the withdrawal program diminished heightened anxiety in alcohol-exposed subjects. Our results highlight the adverse effects of chronic alcohol exposure on the reproductive capacity of both males and females, and underscore the utility of the zebrafish model system to understand the biology of chronic alcoholism. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Isospora belli Infection with Chronic Diarrhea in an Alcoholic Patient

    OpenAIRE

    Kim, Min Jae; Kim, Woo Ho; Jung, Hyun-Chae; Chai, Jee-Won; Chai, Jong-Yil

    2013-01-01

    Chronic diarrhea with a 35 kg weight loss (75 kg to 40 kg) occurred during 2 years in an alcoholic patient was diagnosed with Isospora belli infection in the Republic of Korea. The patient, a 70-year old Korean male, had been a heavy drinker for more than 30 years. He was admitted to the Seoul National University Hospital because of long-standing diarrhea and severe weight loss. He had an increased white blood cell (WBC) count with high peripheral blood eosinophilia (36.8-39.9%) and lowered p...

  17. [An effect of cabergoline on alcohol consumption and DRD2 expression in the brain of rats with chronic alcohol intoxication].

    Science.gov (United States)

    Shamakina, I Yu; Proskuryakova, T V; Shokhonova, V A; Ulyanova, E V; Anokhin, P K; Tapabarko, I E; Anokhina, I P

    2016-01-01

    Cabergoline is a high selective agonist of dopamine D2 receptors (D2R). The activation of D2R plays an important role in the regulation of dopamine transmission, the imbalance of which is thought to underlie the development of alcohol motivation. To examine this possibility, cabergoline effects on alcohol consumption and brain DRD2 expression in rats with chronic alcohol intoxication were studied. Male Wister rats were studied using the following methods: modelling of chronic alcohol intoxication, testing in «10% alcohol vs water» choice regimen, quantitative RT-PCR. Systemic administration of 0.5 mg/kg of cabergoline significantly decreases alcohol intake in alcohol-preferring rats. At the same time, cabergoline elevates the DRD2 expression in the midbrain and striatum of high-alcohol-preferring rats but not in intact (alcohol-naïve) animals. The involvement of cabergoline in the DRD2 expression may lead to the decrease in alcohol motivation. These findings indicate that cabergoline needs further investigations as a new potential medication for alcohol use disorder.

  18. Subjective ratings of prospective memory deficits in chronic heavy alcohol users

    OpenAIRE

    Heffernan, Tom; Moss, Mark; Ling, Jonathan

    2002-01-01

    Chronic alcohol abuse has a detrimental effect on retrospective memory. Less is known about its putative effects on everyday memory. This study looked at self-ratings of prospective memory (PM) (memory for future events). After controlling for other drug and strategy use, chronic heavy alcohol users showed global impairments in PM, when compared to matched controls. The underlying mechanisms are discussed.

  19. Vitamin D supplementation protects against bone loss associated with chronic alcohol administration in female mice

    Science.gov (United States)

    Chronic alcohol consumption is detrimental to bone by decreasing bone mineral density (BMD) resulting in increased risk of osteoporosis risk and fracture, particularly in women. In moderation, alcohol is positively associated with increased BMD and reduced fracture risk. Alcohol's toxic effects ha...

  20. [Effects of alcohol. Besides its harmful health impact, are there any positive aspects of chronic alcohol consumption?].

    Science.gov (United States)

    Meier, Patrick; Seitz, Helmut K

    2006-11-15

    It is well known that chronic alcohol consumption results in a great number of alcohol-associated diseases. In the past 15 years, data showing a protective effect of chronic alcohol consumption have been published, especially with respect to coronary heart disease and ischemic stroke. Already small quantities of alcohol seem to have this protective effect which depends on various individual factors. This is specially pronounced in the elderly and in individuals with additional risk factors for coronary heart disease. An investigation of the German Ministry of Health has clearly shown that poor-risk doses of alcohol in healthy adults are alcohol per day in men and Recommendations of the "German Hauptstelle für Suchtfragen" are based on these data. The present review tries to critically question the protective effect of alcohol on arteriosclerosis. A public recommendation of alcohol as a coronary therapeutic agent would create more damage than benefit. A recommendation of alcohol as protection against myocardial infarction and ischemic stroke cannot be given due to its potential damaging effect on various other organs. In addition, a regular daily administration of alcohol should not be recommended.

  1. Chronic alcohol consumption from adolescence-to-adulthood in mice - hypothalamic gene expression changes in the dilated cardiomyopathy signaling pathway

    OpenAIRE

    Zou, Hong; Wang, Ke; Gao, Yang; Song, Huaiguang; Xie, Qinglian; Jin, Meilei; Zhao, Guoping; Xiao, Huasheng; Yu, Lei

    2014-01-01

    Background Adolescence is a developmental stage vulnerable to alcohol drinking-related problems and the onset of alcoholism. Hypothalamus is a key brain region for food and water intake regulation, and is one of the alcohol-sensitive brain regions. However, it is not known what would be the alcohol effect on hypothalamus following adolescent alcohol intake, chronically over the adolescent development, at moderate levels. Results We employed a paradigm of chronic moderate alcohol intake from a...

  2. The effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment

    DEFF Research Database (Denmark)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina

    2016-01-01

    BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. RSV prevents the development of steatosis in a number of experimental fatty liver (NAFL) models but the preventive or therapeutic effects on experimental NASH are not...

  3. Chronic alcohol ingestion in rats alters lung metabolism, promotes lipid accumulation, and impairs alveolar macrophage functions.

    Science.gov (United States)

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B; Kallen, Caleb B; Lang, Charles H; Summer, Ross

    2014-12-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  4. Chronic periadolescent alcohol consumption produces persistent cognitive deficits in rhesus macaques.

    Science.gov (United States)

    Wright, M Jerry; Taffe, Michael A

    2014-11-01

    Although human alcoholics exhibit lasting cognitive deficits, it can be difficult to definitively rule out pre-alcohol performance differences. For example, individuals with a family history of alcoholism are at increased risk for alcoholism and are also behaviorally impaired. Animal models of controlled alcohol exposure permit balanced group assignment, thereby ruling out the effects of pre-existing differences. Periadolescent male rhesus macaques (N = 5) consumed alcohol during 200 drinking sessions (M-F) across a 10-month period (mean daily alcohol consumption: 1.38 g/kg/day). A control group (N = 5) consumed a fruit-flavored vehicle during the same period. Spatial working memory, visual discrimination learning and retention and response time behavioral domains were assessed with subtests of the Monkey CANTAB (CAmbridge Neuropsychological Test Automated Battery). Spatial working memory performance was impaired in the alcohol group after 120 drinking sessions (6 mo) in a manner that depended on retention interval. The chronic alcohol animals were also impaired in retaining a visual discrimination over 24 hrs when assessed 6-8 weeks after cessation of alcohol drinking. Finally, the presentation of distractors in the response time task impaired the response time and accuracy of the chronic alcohol group more than controls after 6 months of alcohol cessation. Chronic alcohol consumption over as little as 6 months produces cognitive deficits, with some domains still affected after acute (6-8 wks) and lasting (6 mo) discontinuation from drinking. Animals were matched on alcohol preference and behavioral performance prior to exposure, thus providing strong evidence for the causal role of chronic alcohol in these deficits. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. The Cognitive and Behavioural Impact of Alcohol Promoting and Alcohol Warning Advertisements: An Experimental Study

    OpenAIRE

    Brown, Kyle G; Stautz, Kai-Denis; Hollands, Gareth John; Winpenny, Eleanor Margaret; Marteau, Theresa

    2015-01-01

    Aims To assess the immediate effect of alcohol promoting and alcohol warning advertisements on implicit and explicit attitudes towards alcohol and on alcohol seeking behaviour. Methods We conducted a between-participants online experiment in which participants were randomly assigned to view one of three sets of advertisements: (a) alcohol promoting, (b) alcohol warning, or (c) unrelated to alcohol. A total of 373 participants (59.5% female) aged 18?40 (M = 28.03) living in the UK were recruit...

  6. Chronic alcohol consumption impairs visuo-spatial associative memory in periadolescent rhesus monkeys.

    Science.gov (United States)

    Crean, Rebecca D; Vandewater, Sophia A; Katner, Simon N; Huitron-Resendiz, Salvador; Taffe, Michael A

    2011-03-01

    Alcohol abuse in the adult is often preceded by high alcohol consumption during adolescence. Profound changes in brain structure and function occur during this developmental period, therefore alcohol may impact essential cognitive skill development during the formal educational years. The objective of this study was to determine if chronic oral alcohol intake slows acquisition and performance of cognitive tasks in male adolescent rhesus monkeys. Treatment groups (Alcohol, N=4; Control, N=3) were evaluated on bimanual dexterity and tests of visuo-spatial memory and learning adapted from the Cambridge Neuropsychological Test Automated Battery. Animals were trained daily in 30 min sessions and had subsequent access to alcohol/Tang® solutions (Alcohol group) or Tang® only (Control group) Monday through Friday for 11 months. Recordings of brainstem auditory evoked potentials (BSAEP) were conducted periodically before and during the chronic drinking. Chronic alcohol drinking (ave of 1.78 g/kg alcohol per session) impaired behavioral performance assessed ∼22 h after the prior drinking session. The Alcohol group required more trials than the Control group to reach criterion on the visuo-spatial memory task and showed increased sensitivity to trial difficulty and retention interval. Alcohol animals also had slowed initial acquisition of the bimanual task. The latency of P4 and P5 BSAEP peaks were also delayed in the Alcohol group. Chronic alcohol consumption impaired the acquisition and performance of a spatial memory task and disrupted brainstem auditory processing, thus these results show that repeated alcohol exposure in adolescence interferes with a range of brain functions including complex visuo-spatial mnemonic processing. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. An experimental trial exploring the impact of continuous transdermal alcohol monitoring upon alcohol consumption in a cohort of male students.

    Directory of Open Access Journals (Sweden)

    Fergus G Neville

    Full Text Available To examine the impact of continuous transdermal alcohol monitoring upon alcohol consumption in male students at a Scottish university.Using a within-subject mixed-methods design, 60 male university students were randomly allocated into three experimental conditions using AUDIT score stratified sampling. Participants in Conditions A and B were asked not to consume alcohol for a 14-day period, with those in Condition A additionally being required to wear a continuous transdermal alcohol monitoring anklet. Condition C participants wore an anklet and were asked to continue consuming alcohol as normal. Alcohol consumption was measured through alcohol timeline follow-back, and using data collected from the anklets where available. Diaries and focus groups explored participants' experiences of the trial.Alcohol consumption during the 14-day trial decreased significantly for participants in Conditions A and B, but not in C. There was no significant relative difference in units of alcohol consumed between Conditions A and B, but significantly fewer participants in Condition A drank alcohol than in Condition B. Possible reasons for this difference identified from the focus groups and diaries included the anklet acting as a reminder of commitment to the study (and the agreement to sobriety, participants feeling under surveillance, and the use of the anklet as a tool to resist social pressure to consume alcohol.The study provided experience in using continuous transdermal alcohol monitors in an experimental context, and demonstrated ways in which the technology may be supportive in facilitating sobriety. Results from the study have been used to design a research project using continuous transdermal alcohol monitors with ex-offenders who recognise a link between their alcohol consumption and offending behaviour.

  8. Intensive care unit stay is prolonged in chronic alcoholic men following tumor resection of the upper digestive tract.

    Science.gov (United States)

    Spies, C D; Nordmann, A; Brummer, G; Marks, C; Conrad, C; Berger, G; Runkel, N; Neumann, T; Müller, C; Rommelspacher, H; Specht, M; Hannemann, L; Striebel, H W; Schaffartzik, W

    1996-07-01

    The prevalence of chronic alcohol misuse in patients with oral, pharyngeal, laryngeal or esophageal carcinomas exceeds 60%. No data is available, to our knowledge, on the morbidity and mortality of chronic alcoholics in surgical intensive care units (ICU) following tumor resection. We investigated whether the subsequent ICU stay in chronic alcoholics following tumor resection was prolonged and whether the incidence of pneumonia and sepsis was increased. 213 patients with carcinomas of the upper digestive tract were evaluated regarding their drinking habits. Chronic alcoholics met either the DSM-III-R criteria for alcohol abuse or dependence. Conventional laboratory markers and serum carbohydrate-deficient transferrin were determined preoperatively. Major intercurrent complications during ICU stay such as an alcohol withdrawal syndrome, pneumonia and sepsis as well as the frequency of death were documented. Patients did not differ significantly between groups regarding age or APACHE score on admission to the ICU.121 patients were diagnosed as being chronic alcoholics, 39 as being social drinkers and 61 as being non-alcoholics. In chronic alcoholics the frequency of death was significantly increased. Due to the increased incidence of pneumonia and sepsis the ICU stay was significantly prolonged in chronic alcoholics by approximately 8 days. The increased mortality and morbidity rate demonstrates that chronic alcoholics undergoing major tumor surgery have to be considered as high-risk patients during their postoperative ICU stay. Further studies are required with respect to the immuno-competence of chronic alcoholics and the prevention of alcohol withdrawal syndrome, pneumonia and sepsis in these patients.

  9. [Impact of harmful consumption of alcohol in accident-related mortality and chronic diseases in Mexico].

    Science.gov (United States)

    Guerrero-López, Carlos Manuel; Muños-Hernández, José Alberto; Sáenz de Miera-Juárez, Belén; Pérez-Núñez, Ricardo; Reynales-Shigematsu, Luz Myriam

    2013-01-01

    To analyze alcohol consumption, and its impact on road traffic-related mortality and chronic diseases. Through the analysis of national health surveys, registry of traffic collisions, mortality records and economic surveys, we estimated prevalence, mortality and consumption indicators. Between 2000 and 2012, alcohol consumption in adolescents remained stable, with a significant increase among adults. Traffic collision rates related with alcohol were 0.36 and 0.58 among adolescents and adults, respectively; 8.4% of the population who suffered traffic injuries was under alcohol effects when the accident occurred. The trend in mortality from two alcohol-attributable diseases has been constant, with an average of 18 000 deaths per year. Alcohol abuse causes serious health damages. Tax raises to alcohol, along with other policies, could reduce harmful alcohol consumption and its associated mortality.

  10. The Cognitive and Behavioural Impact of Alcohol Promoting and Alcohol Warning Advertisements: An Experimental Study.

    Science.gov (United States)

    Brown, Kyle G; Stautz, Kaidy; Hollands, Gareth J; Winpenny, Eleanor M; Marteau, Theresa M

    2016-05-01

    To assess the immediate effect of alcohol promoting and alcohol warning advertisements on implicit and explicit attitudes towards alcohol and on alcohol seeking behaviour. We conducted a between-participants online experiment in which participants were randomly assigned to view one of three sets of advertisements: (a) alcohol promoting, (b) alcohol warning, or (c) unrelated to alcohol. A total of 373 participants (59.5% female) aged 18-40 (M = 28.03) living in the UK were recruited online through a research agency. Positive and negative implicit attitudes and explicit attitudes towards alcohol were assessed before and after advertisements were viewed. Alcohol seeking behaviour was measured by participants' choice of either an alcohol-related or non-alcohol-related voucher offered ostensibly as a reward for participation. Self-reported past week alcohol consumption was also recorded. There were no main effects on any of the outcome measures. In heavier drinkers, viewing alcohol promoting advertisements increased positive implicit attitudes (standardized beta = 0.15, P = 0.04) and decreased negative implicit attitudes (standardized beta = -0.17, P = 0.02). In heavier drinkers, viewing alcohol warning advertisements decreased negative implicit attitudes (standardized beta = -0.19, P = 0.01). Viewing alcohol promoting advertisements has a cognitive impact on heavier drinkers, increasing positive and reducing negative implicit attitudes towards alcohol. Viewing alcohol warning advertisements reduces negative implicit attitudes towards alcohol in heavier drinkers, suggestive of a reactance effect. © The Author 2015. Medical Council on Alcohol and Oxford University Press.

  11. Temirtau Dust Chronic Exposure on Experimental Animals

    Directory of Open Access Journals (Sweden)

    Ludmila Т. Bazeluk

    2013-01-01

    Full Text Available The article presents cytomorphological research of rats’ bronchoalveolar fluid, gaster, thyroid, liver and kidneys cells. The experimental results showed that cytotoxic effect on rats’ of both sexes was observed during inhalation of Timirtau (Republic of Kazakhstan dust in the dose of 0.15 mg/mL for the period of 4 months.

  12. The effect of alcohol advertising on immediate alcohol consumption in college students: An experimental study

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Engels, R.C.M.E.

    2012-01-01

    Background: Survey studies have emphasized a positive association between exposure to alcohol advertising on television (TV) and the onset and continuation of drinking among young people. Alcohol advertising might also directly influence viewers’ consumption of alcohol while watching TV. The

  13. Is memory impairment greater than cognitive impairment in moderate chronic alcoholics?

    Science.gov (United States)

    Capitani, E; Della Pria, M; Doro, G; Spinnler, H

    1983-12-01

    The aims of the research were to test (i) whether moderate chronic alcoholics (A/pts) perform worse than non teetotaler controls (C/pts) either on memory or on intelligence tasks or on both, and (ii) whether there was a significant difference between verbal and spatial memory scores pointing to the claimed prevailing right hemisphere sensitivity to alcohol abuse. Great care was taken in selecting C/pts not to exaggerate by sample biasing the psychological effects of alcoholism. Intelligence was tested by means of verbal and performance Wechsler-Bellevue IQ and Raven PM47; memory was tested by means of serial immediate memory span and learning by means of verbal and spatial devices. The results support the conclusion that chronic wine alcoholism in a band of drinkers with lowish educational background and very set drinking habits impairs memory and intelligence without any significant difference. Moreover there is no evidence of a prevalent right hemisphere sensitivity to chronic alcohol addiction.

  14. The Cognitive and Behavioural Impact of Alcohol Promoting and Alcohol Warning Advertisements: An Experimental Study

    Science.gov (United States)

    Brown, Kyle G.; Stautz, Kaidy; Hollands, Gareth J.; Winpenny, Eleanor M.; Marteau, Theresa M.

    2016-01-01

    Aims To assess the immediate effect of alcohol promoting and alcohol warning advertisements on implicit and explicit attitudes towards alcohol and on alcohol seeking behaviour. Methods We conducted a between-participants online experiment in which participants were randomly assigned to view one of three sets of advertisements: (a) alcohol promoting, (b) alcohol warning, or (c) unrelated to alcohol. A total of 373 participants (59.5% female) aged 18–40 (M = 28.03) living in the UK were recruited online through a research agency. Positive and negative implicit attitudes and explicit attitudes towards alcohol were assessed before and after advertisements were viewed. Alcohol seeking behaviour was measured by participants' choice of either an alcohol-related or non-alcohol-related voucher offered ostensibly as a reward for participation. Self-reported past week alcohol consumption was also recorded. Results There were no main effects on any of the outcome measures. In heavier drinkers, viewing alcohol promoting advertisements increased positive implicit attitudes (standardized beta = 0.15, P = 0.04) and decreased negative implicit attitudes (standardized beta = −0.17, P = 0.02). In heavier drinkers, viewing alcohol warning advertisements decreased negative implicit attitudes (standardized beta = −0.19, P = 0.01). Conclusions Viewing alcohol promoting advertisements has a cognitive impact on heavier drinkers, increasing positive and reducing negative implicit attitudes towards alcohol. Viewing alcohol warning advertisements reduces negative implicit attitudes towards alcohol in heavier drinkers, suggestive of a reactance effect. PMID:26391367

  15. Isospora belli Infection with Chronic Diarrhea in an Alcoholic Patient

    Science.gov (United States)

    Kim, Min Jae; Kim, Woo Ho; Jung, Hyun-Chae; Chai, Jee-Won

    2013-01-01

    Chronic diarrhea with a 35 kg weight loss (75 kg to 40 kg) occurred during 2 years in an alcoholic patient was diagnosed with Isospora belli infection in the Republic of Korea. The patient, a 70-year old Korean male, had been a heavy drinker for more than 30 years. He was admitted to the Seoul National University Hospital because of long-standing diarrhea and severe weight loss. He had an increased white blood cell (WBC) count with high peripheral blood eosinophilia (36.8-39.9%) and lowered protein and albumin levels but without any evidence of immunosuppression. A parasitic infection was suspected and fecal examination was repeated 3 times with negative results. Peroral endoscopy with mural biopsy was performed in the upper jejunum. The biopsy specimens revealed villous atrophy with loss of villi together with various life cycle stages of I. belli, including trophozoites, schizonts, merozoites, macrogamonts, and microgamonts. The patient was treated successfully with oral doses of trimethoprim 160-320 mg and sulfamethoxazole 800-1,600 mg daily for 4 weeks. A follow-up evaluation at 2.5 years later revealed marked improvement of body weight (68 kg), increased protein and albumin levels, and normal WBC count with low eosinophils (3.1%). This is the first clinical case of isoporiasis with demonstration of various parasitic stages in the Republic of Korea. PMID:23710089

  16. [Effect of puerarin in myocardial protection in rats with acute and chronic alcoholism].

    Science.gov (United States)

    Cui, Shu-qin

    2011-12-01

    To investigate the protective effect of puerarin on the myocardium of rats with acute and chronic alcoholism. In acute alcoholism experiment, normal male SD rats were randomly divided into the control group, alcoholism group and puerarin group (n=8), and high- and low-dose puerarin was administered. In chronic alcoholism experiment, increasing puerarin doses were given. Serum and myocardial levels of spartate aminotransferase (AST) and creatine phosphokinase (CPK) were determined using enzymatic methed, and superoxide dismutase (SOD), malondialdehyde (MDA), Ca(2+)-Mg(2+)-ATPase, and Na(+)-K(+)-ATPase in the myocardium were assayed with colorimetric method. HE staining was used to observe the microscopic changes of the myocardium. Compared with alcoholism group, puerarin-treated groups showed significantly lowered myocardial contents of MDA, CPK and AST and serum levels of AST and CPK (P0.05). HE staining of the myocardium showed cell swelling and obscure cell boundaries in alcoholism group, especially in chronic alcoholism group. The myocardial structure in puerarin group remained clear and regular. Puerarin can protect from myocardial injuries induced by acute and chronic alcoholism in rats.

  17. The contribution of alcohol to chronic liver disease in patients from ...

    African Journals Online (AJOL)

    Objective: This study aimed at determining the level and type of alcohol consumed by patients diagnosed with chronic liver disease (CLD) and, hence, the extent to which alcohol may have contributed to the development of the condition. Study Design: Patients with diagnosis ofCLDwere consecutively recruited and a ...

  18. Buss-Durkee Assessment and Validation with Violent versus Nonviolent Chronic Alcohol Abusers.

    Science.gov (United States)

    Renson, Gisele J.; And Others

    1978-01-01

    Chronic alcohol abusers who had been violent while intoxicated and nonviolent alcohol abusers were administered the Buss-Durkee Inventory. Violence was documented. Violent drinkers scored significantly higher than control subjects on the inventory total hostility score and on subscales measuring assault, irritability, verbal hostility, indirect…

  19. Alcohol abuse and dependence criteria as predictors of a chronic course of alcohol use disorders in the general population

    NARCIS (Netherlands)

    de Bruijn, Carla; van den Brink, Wim; de Graaf, Ron; Vollebergh, Wilma A. M.

    2005-01-01

    Aims: To investigate whether DSM-IV abuse and dependence criteria and the ICD-10 criterion for craving differentially predict a chronic course of alcohol use disorders (AUD) in the general population. Methods: Data were derived from the Netherlands Mental Health Survey and Incidence Study, a large

  20. Chronic alcohol consumption increases the expression of uncoupling protein-2 and -4 in the brain.

    Science.gov (United States)

    Graw, Jan A; von Haefen, Clarissa; Poyraz, Deniz; Möbius, Nadine; Sifringer, Marco; Spies, Claudia D

    2013-10-01

    Chronic alcohol consumption leads to oxidative stress in a variety of cells, especially in brain cells because they have a reduced oxidative metabolism of alcohol. Uncoupling proteins (UCPs) are anion channels of the inner mitochondrial membrane, which can decouple internal respiration. "Mild uncoupling" of the mitochondrial respiratory chain leads to a reduced production of free radicals (reactive oxygen species) and a reduction in oxidative cell stress. The extent to which chronic alcohol consumption regulates UCP-2 and -4 in the brain is still unknown. We examined the effects of a 12-week 5% alcohol diet in the brain of male Wistar rats (n = 34). Cerebral gene and protein expression of UCP-2, -4, as well as Bcl-2, and the release of cytochrome c out of the mitochondria were detected by real-time polymerase chain reaction and Western blot analysis. The percentage of degenerated cells was determined by Fluoro-Jade B staining of brain slices. Brains of rats with a chronic alcohol diet showed an increased gene and protein expression of UCP-2 and -4. The expression of the antiapoptotic protein Bcl-2 in the brain of the alcohol-treated animals was decreased significantly, whereas cytochrome c release from mitochondria was increased. In addition increased neurodegeneration could be demonstrated in the alcohol-treated animals. Chronic alcohol consumption leads to a cerebral induction of UCP-2 and -4 with a simultaneous decrease in the antiapoptotic protein Bcl-2, cytochrome c release from mitochondria and increased neurodegeneration. This study reveals a compensatory effect of UCP-2 and -4 in the brain during chronic alcohol consumption. Copyright © 2013 by the Research Society on Alcoholism.

  1. Chronic alcohol consumption enhances iNKT cell maturation and activation.

    Science.gov (United States)

    Zhang, Hui; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G

    2015-01-15

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1(-) iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1(+)CD44(hi) mature iNKT cells but does not alter the number of NK1.1(-) immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1(-) iNKT cells, especially the NK1.1(-)CD44(lo) Stage I iNKT cells. The percentage of NKG2A(+) iNKT cells increases in all of the tissues and organs examined; whereas CXCR3(+) iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Alcohol consumers’ attention to warning labels and brand information on alcohol packaging: Findings from cross-sectional and experimental studies

    Directory of Open Access Journals (Sweden)

    Inge Kersbergen

    2017-01-01

    Full Text Available Abstract Background Alcohol warning labels have a limited effect on drinking behavior, potentially because people devote minimal attention to them. We report findings from two studies in which we measured the extent to which alcohol consumers attend to warning labels on alcohol packaging, and aimed to identify if increased attention to warning labels is associated with motivation to change drinking behavior. Methods Study 1 (N = 60 was an exploratory cross-sectional study in which we used eye-tracking to measure visual attention to brand and health information on alcohol and soda containers. In study 2 (N = 120 we manipulated motivation to reduce drinking using an alcohol brief intervention (vs control intervention and measured heavy drinkers’ attention to branding and warning labels with the same eye-tracking paradigm as in study 1. Then, in a separate task we experimentally manipulated attention by drawing a brightly colored border around health (or brand information before measuring participants’ self-reported drinking intentions for the subsequent week. Results Study 1 showed that participants paid minimal attention to warning labels (7% of viewing time. Participants who were motivated to reduce drinking paid less attention to alcohol branding and alcohol warning labels. Results from study 2 showed that the alcohol brief intervention decreased attention to branding compared to the control condition, but it did not affect attention to warning labels. Furthermore, the experimental manipulation of attention to health or brand information did not influence drinking intentions for the subsequent week. Conclusions Alcohol consumers allocate minimal attention to warning labels on alcohol packaging and even if their attention is directed to these warning labels, this has no impact on their drinking intentions. The lack of attention to warning labels, even among people who actively want to cut down, suggests that there is room for

  3. Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior.

    Science.gov (United States)

    Cannady, Reginald; Rinker, Jennifer A; Nimitvilai, Sudarat; Woodward, John J; Mulholland, Patrick J

    2018-01-28

    Neural mechanisms underlying alcohol use disorder remain elusive, and this lack of understanding has slowed the development of efficacious treatment strategies for reducing relapse rates and prolonging abstinence. While synaptic adaptations produced by chronic alcohol exposure have been extensively characterized in a variety of brain regions, changes in intrinsic excitability of critical projection neurons are understudied. Accumulating evidence suggests that prolonged alcohol drinking and alcohol dependence produce plasticity of intrinsic excitability as measured by changes in evoked action potential firing and after-hyperpolarization amplitude. In this chapter, we describe functional changes in cell firing of projection neurons after long-term alcohol exposure that occur across species and in multiple brain regions. Adaptations in calcium-activated (K Ca 2), voltage-dependent (K V 7), and G protein-coupled inwardly rectifying (K ir 3 or GIRK) potassium channels that regulate the evoked firing and after-hyperpolarization parallel functional changes in intrinsic excitability induced by chronic alcohol. Moreover, there are strong genetic links between alcohol-related behaviors and genes encoding K Ca 2, K V 7, and GIRK channels, and pharmacologically targeting these channels reduces alcohol consumption and alcohol-related behaviors. Together, these studies demonstrate that chronic alcohol drinking produces adaptations in K Ca 2, K V 7, and GIRK channels leading to impaired regulation of the after-hyperpolarization and aberrant cell firing. Correcting the deficit in the after-hyperpolarization with positive modulators of K Ca 2 and K V 7 channels and altering the GIRK channel binding pocket to block the access of alcohol represent a potentially highly effective pharmacological approach that can restore changes in intrinsic excitability and reduce alcohol consumption in affected individuals.

  4. Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Talamini, G; Bassi, C; Falconi, M; Sartori, N; Salvia, R; Rigo, L; Castagnini, A; Di Francesco, V; Frulloni, L; Bovo, P; Vaona, B; Angelini, G; Vantini, I; Cavallini, G; Pederzoli, P

    1999-07-01

    The aim of this study was to compare alcohol and smoking as risk factors in the development of chronic pancreatitis and pancreatic cancer. We considered only male subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47 extrapancreatic cancers; (2) 69 patients with histologically well documented pancreatic cancer and no clinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona polling list and submitted to a complete medical check-up. Chronic pancreatitis subjects drink more than control subjects and more than subjects with pancreatic cancer without chronic pancreatitis (Ppancreatitis is significantly higher than that in the control group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; Ppancreatic carcinomas but with no history of chronic pancreatitis (OR 5.3; 95% CI 3.0-9.4; Prisk of chronic pancreatitis correlates both with alcohol intake and with cigarette smoking with a trend indicating that the risk increases with increased alcohol intake and cigarette consumption; (2) alcohol and smoking are statistically independent risk factors for chronic pancreatitis; and (3) the risk of pancreatic cancer correlates positively with cigarette smoking but not with drinking.

  5. Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis

    Science.gov (United States)

    Treutlein, Jens; Streit, Fabian; Juraeva, Dilafruz; Degenhardt, Franziska; Rietschel, Liz; Forstner, Andreas J.; Ridinger, Monika; Dukal, Helene; Foo, Jerome C.; Soyka, Michael; Maier, Wolfgang; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Müller-Myhsok, Bertram; Lucae, Susanne; Ising, Marcus; Stickel, Felix; Berg, Thomas; Roggenbuck, Ulla; Jöckel, Karl-Heinz; Scholz, Henrike; Zimmermann, Ulrich S.; Buch, Stephan; Sommer, Wolfgang H.; Spanagel, Rainer; Brors, Benedikt; Cichon, Sven; Mann, Karl; Kiefer, Falk; Hampe, Jochen; Rosendahl, Jonas; Nöthen, Markus M.; Rietschel, Marcella

    2017-01-01

    The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10−6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed. PMID:28714907

  6. [The expression and significance of VIP and its receptor in the cochlea of different degrees of chronic alcoholism rats].

    Science.gov (United States)

    Feng, Jing; Liu, Haibing

    2015-07-01

    To determine whether chronic alcoholism alters the expression levels of Vasoactive intestinal polypeptide (VIP) and its receptor (VIPR1) in the cochlea of chronic alcoholism rats. We measured their expression levels in 30 SD rats, in which we created models of different degrees of chronic alcoholism. We investigated the presence of the mRNA of VIP in the cochlea of chronic alcoholism rats and controls by reverse transcription-polymerase chain reaction (RT-PCR) method. We investigated the presence of proteins of VIPR1 in poisoned rats and controls by western blot. We also evaluated the local distribution of VIP cells by immunohistochemistry. We found that the levels of VIP and VIPR1 were downregulated in the chronic alcoholism groups compared to the controls group. The differences in some expression levels were significant different between chronic alcoholism rats and control rats. Moreover, at different degrees of alcohol poisoning in rats, the contents of VIP and VIPR1 differed. Decreased levels of VIP and VIPR1 were detected in the deep chronic alcoholism group compared to the group with low-degree poisoning (P 0.05). These results suggest that VIP and VIPR1 play an important role in the auditory function in rats with chronic alcoholism. Chronic alcoholism may cause a peptide hormone secretion imbalance in the auditory system, eventually leading to hearing loss.

  7. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    Science.gov (United States)

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms. Copyright © 2014 the American Physiological Society.

  8. The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats

    Science.gov (United States)

    Reed, Adam H.; McCarty, Heidi L.; Evans, Glenda L.; Turner, Russell T.; Westerlind, Kim C.

    2002-01-01

    BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no

  9. Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

    Science.gov (United States)

    Sharma, Bhawana; Dabur, Rajesh

    2016-01-01

    Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels. Furthermore, effects of Tinospora cordifolia water extract (TCE) (hepatoprotective) on vitamin excretion and intestinal absorption were also studied. In the study, asymptomatic moderate alcoholics (n = 12) without chronic liver disease and healthy volunteers (n = 14) of mean age 39 ± 2.2 (mean ± SD) were selected and divided into three groups. TCE treatment was performed for 14 days. The blood and urine samples were collected on Day 0 and 14 after treatment with TCE and analyzed. In alcoholics samples, a significant increase in the levels of gamma-glutamyl transferase, aspartate transaminase, alanine transaminase, Triglyceride, Cholesterol, HDL and LDL (P alcoholic samples; however, TCE intervention restored the CA and biotin levels. Vitamin metabolism biomarkers, i.e. homocysteine and xanthurenic acid, were also normalized after TCE intervention. Overall data depict that moderate alcohol intake is also hepatotoxic and decreases intestinal absorption. However, TCE treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  10. Alcohol and smoking behavior in chronic pain patients: the role of opioids

    DEFF Research Database (Denmark)

    Ekholm, Ola; Grønbaek, Morten; Peuckmann, Vera

    2008-01-01

    The primary aim of this epidemiological study was to investigate associations between chronic non-cancer pain with or without opioid treatment and the alcohol and smoking behavior. The secondary aims were to investigate self-reported quality of life, sleeping problems, oral health and the use...... individuals. We found, that individuals suffering from chronic pain were less likely to drink alcohol. In opioid users alcohol consumption was further reduced. Cigarette smoking was significantly increased in individuals suffering from chronic pain and in opioid users smoking was further increased. Poor oral...... of different health care providers. The Danish health survey of 2005 was based on a region-stratified random sample of 10.916 individuals. Data were collected via personal interviews and self-administrated questionnaires. Respondents suffering from chronic pain were identified through the question 'Do you have...

  11. Neuroadaptations in human chronic alcoholics: dysregulation of the NF-kappaB system.

    Directory of Open Access Journals (Sweden)

    Anna Okvist

    2007-09-01

    Full Text Available Alcohol dependence and associated cognitive impairments apparently result from neuroadaptations to chronic alcohol consumption involving changes in expression of multiple genes. Here we investigated whether transcription factors of Nuclear Factor-kappaB (NF-kappaB family, controlling neuronal plasticity and neurodegeneration, are involved in these adaptations in human chronic alcoholics.Analysis of DNA-binding of NF-kappaB (p65/p50 heterodimer and the p50 homodimer as well as NF-kappaB proteins and mRNAs was performed in postmortem human brain samples from 15 chronic alcoholics and 15 control subjects. The prefrontal cortex involved in alcohol dependence and cognition was analyzed and the motor cortex was studied for comparison. The p50 homodimer was identified as dominant kappaB binding factor in analyzed tissues. NF-kappaB and p50 homodimer DNA-binding was downregulated, levels of p65 (RELA mRNA were attenuated, and the stoichiometry of p65/p50 proteins and respective mRNAs was altered in the prefrontal cortex of alcoholics. Comparison of a number of p50 homodimer/NF-kappaB target DNA sites, kappaB elements in 479 genes, down- or upregulated in alcoholics demonstrated that genes with kappaB elements were generally upregulated in alcoholics. No significant differences between alcoholics and controls were observed in the motor cortex.We suggest that cycles of alcohol intoxication/withdrawal, which may initially activate NF-kappaB, when repeated over years downregulate RELA expression and NF-kappaB and p50 homodimer DNA-binding. Downregulation of the dominant p50 homodimer, a potent inhibitor of gene transcription apparently resulted in derepression of kappaB regulated genes. Alterations in expression of p50 homodimer/NF-kappaB regulated genes may contribute to neuroplastic adaptation underlying alcoholism.

  12. Clozapine chronically suppresses alcohol drinking in Syrian golden hamsters

    Science.gov (United States)

    Chau, David T.; Gulick, Danielle; Xie, Haiyi; Dawson, Ree; Green, Alan I.

    2015-01-01

    Alcohol use disorder is common in patients with schizophrenia and is associated with poor clinical outcomes. Preliminary reports from our group and others suggest that the atypical antipsychotic clozapine may decrease alcohol use in these patients. We have previously shown that clozapine suppresses alcohol consumption for 9 days in Syrian golden hamsters. Here, we assessed the effects of clozapine on alcohol consumption in hamsters over a 27-day period, using a continuous access, 2-bottle (15% alcohol vs. water) protocol. Clozapine (4, 8, or 12 mg/kg/day, injected subcutaneously [s.c.]) dose-dependently suppressed alcohol drinking, while increasing food and water intake, and there was no tolerance within individual groups to this effect of clozapine over time. In a separate experiment, the effects of clozapine on sucrose and water drinking and food intake over a 9-day period were assessed. Clozapine (4, 8, or 12 mg/kg/day s.c.) failed to suppress sucrose (0.09 M), food, or water consumption at any time-point tested. In a related study, assessment of blood alcohol levels in hamsters indicated that blood alcohol levels were maintained within a narrow and moderate range (7–13 mg/dL), levels noted by others to produce physiologic effects in rodents. The ability of clozapine to suppress alcohol drinking in the hamster over an extended period of time without suppressing sucrose, water, or food consumption is consistent with preliminary reports indicating that clozapine limits frequent alcohol use, even producing abstinence in many patients with schizophrenia. PMID:19895824

  13. The effect of alcohol advertising on immediate alcohol consumption in college students: an experimental study

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Engels, R.C.M.E.

    2012-01-01

    Background:  Survey studies have emphasized a positive association between exposure to alcohol advertising on television (TV) and the onset and continuation of drinking among young people. Alcohol advertising might also directly influence viewers’ consumption of alcohol while watching TV. The

  14. Chronic Alcohol Exposure is Associated with Decreased Neurogenesis, Aberrant Integration of Newborn Neurons, and Cognitive Dysfunction in Female Mice.

    Science.gov (United States)

    Golub, Haleigh M; Zhou, Qi-Gang; Zucker, Hannah; McMullen, Megan R; Kokiko-Cochran, Olga Nicole; Ro, Eun Jeoung; Nagy, Laura E; Suh, Hoonkyo

    2015-10-01

    Neurological deficits of alcohol use disorder (AUD) have been attributed to dysfunctions of specific brain structures. Studies of alcoholic patients and chronic alcohol exposure animal models consistently identify reduced hippocampal mass and cogntive dysfunctions as a key alcohol-induced brain adaptation. However, the precise substrate of chronic alcohol exposure that leads to structural and functional impairments of the hippocampus is largely unknown. Using a calorie-matched alcohol feeding method, we tested whether chronic alcohol exposure targets neural stem cells and neurogenesis in the adult hippocampus. The effect of alcohol on proliferation of neural stem cells as well as cell fate determination and survival of newborn cells was evaluated via bromodeoxyuridine pulse and chase methods. A retrovirus-mediated single-cell labeling method was used to determine the effect of alcohol on the morphological development and circuitry incorporation of individual hippocampal newborn neurons. Finally, novel object recognition (NOR) and Y-maze tests were performed to examine whether disrupted neurogenesis is associated with hippocampus-dependent functional deficits in alcohol-fed mice. Chronic alcohol exposure reduced proliferation of neural stem cells and survival rate of newborn neurons; however, the fate determination of newborn cells remained unaltered. Moreover, the dendritic spine density of newborn neurons significantly decreased in alcohol-fed mice. Impaired spine formation indicates that alcohol interfered the synaptic connectivity of newborn neurons with excitatory neurons originating from various areas of the brain. In the NOR test, alcohol-fed mice displayed deficits in the ability to discriminate the novel object. Our study revealed that chronic alcohol exposure disrupted multiple steps of neurogenesis, including the production and development of newborn neurons. In addition, chronic alcohol exposure altered connectivity of newborn neurons with other input

  15. Decrease in salivary lactoferrin output in chronically intoxicated alcohol-dependent patients

    Directory of Open Access Journals (Sweden)

    Napoleon Waszkiewicz

    2012-07-01

    Full Text Available

    Salivary lactoferrin is a glycoprotein involved in the elimination of pathogens and the prevention of massive overgrowth of microorganisms that affect oral and general health. A high concentration of lactoferrin in saliva is often considered to be a marker of damage to the salivary glands, gingivitis, or leakage through inflamed or damaged oral mucosa, infiltrated particularly by neutrophils. We conducted a study to determine the effect of chronic alcohol intoxication on salivary lactoferrin concentration and output. The study included 30 volunteers consisting of ten non-smoking male patients after chronic alcohol intoxication (group A, and 20 control nonsmoking male social drinkers (group C with no history of alcohol abuse. Resting whole saliva was collected 24 to 48 hours after a chronic alcohol intoxication period. Lactoferrin was assessed by enzyme-linked immunosorbent assay. For all participants, the DMFT index (decayed, missing, or filled teeth, gingival index (GI and papilla bleeding index (PBI were assessed. The differences between groups were evaluated using the Mann–Whitney U test. We noticed significantly decreased salivary flow (SF in alcohol dependent patients after chronic alcohol intoxication (A, compared to the control group (C. Although there was no significant difference in salivary lactoferrin concentration between the alcohol dependent group A and the control group C, we found significantly decreased lactoferrin output in group A compared to group C. We found a significant correlation between the amount of daily alcohol use and a decrease in lactoferrin output. There was a significant increase in GI and a tendency of PBI to increase in group A compared to group C. We demonstrated that chronic alcohol intoxication decreases SF and lactoferrin output. The decreased lactoferrin output in persons chronically intoxicated by alcohol may be the result of lactoferrin exhaustion during drinking (due to its alcohol-related lower

  16. Experimental models of non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Kucera, Otto; Cervinkova, Zuzana

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease.

  17. [Effects of polydatin on learning and memory and Cdk5 kinase activity in the hippocampus of rats with chronic alcoholism].

    Science.gov (United States)

    Li, Xin-juan; Zhang, Yan; Xu, Chun-yang; Li, Shuang; Du, Ai-lin; Zhang, Li-bin; Zhang, Rui-ling

    2015-03-01

    To observe the effects of polydatin on learning and memory and cyclin-dependent kinase 5 (Cdk5) kinase activity in the hippocampus of rats with chronic alcoholism. Forty rats were randomly divided into 4 groups: control group, chronic alcoholism group, low and high polydatin group. The rat chronic alcoholism model was established by ethanol 3.0 g/(kg · d) (intragastric administration). The abstinence scoring was used to evaluate the rats withdrawal symptoms; cognitive function was measured by Morris water maze experiment; Cdk5 protein expression in the hippocampus was detected by immunofluorescence; Cdk5 kinase activity in the hippocampus was detected by liquid scintillation counting method. The abstinence score, escape latency, Cdk5 kinase activity in chronic alcoholism group rats were significantly higher than those of control group (P < 0.05). The abstinence score, escape latency in high polydatin group rats were significantly lower than those of chronic alcoholism group (P < 0.05); Cdk5 kinase activity in high and low polydatin group rats was significantly lower than that of chronic alcoholism group( P < 0.05); immunofluorescence showed that the Cdk5 positive cells of chronic alcoholism group were significantly increased compared with control group (P < 0.05), and the Cdk5 positive cells of polydatin groups were significantly decreased compared with chronic alcoholism group ( P < 0.05). Polydatin-reduced the chronic alcoholism damage may interrelate with regulation of Cdk5 kinase activity.

  18. Uptake of ascorbic acid by pancreatic acinar cells is negatively impacted by chronic alcohol exposure.

    Science.gov (United States)

    Subramanian, Veedamali S; Srinivasan, Padmanabhan; Said, Hamid M

    2016-07-01

    Vitamin C (ascorbic acid, AA) is indispensable for normal metabolism of all mammalian cells including pancreatic acinar cells (PACs). PACs obtain AA from their surroundings via transport across the cell membrane. Chronic alcohol exposure negatively affects body AA homeostasis; it also inhibits uptake of other micronutrients into PACs, but its effect on AA uptake is not clear. We examined this issue using both in vitro (266-6 cells) and in vivo (mice) models of chronic alcohol exposure. First, we determined the relative expression of the AA transporters 1 and 2 [i.e., sodium-dependent vitamin C transporter-1 (SVCT-1) and SVCT-2] in mouse and human PACs and found SVCT-2 to be the predominant transporter. Chronic exposure of 266-6 cells to alcohol significantly inhibited AA uptake and caused a marked reduction in SVCT-2 expression at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Similarly, chronic alcohol feeding of mice significantly inhibited AA uptake and caused a marked reduction in level of expression of the SVCT-2 protein, mRNA, and hnRNA. These findings suggest possible involvement of transcriptional mechanism(s) in mediating chronic alcohol effect on AA uptake by PACs. We also observed significant epigenetic changes (histone modifications) in the Slc23a2 gene (reduction in H3K4me3 level and an increase in H3K27me3 level) in the alcohol-exposed 266-6 cells. These findings show that chronic alcohol exposure inhibits PAC AA uptake and that the effect is mediated, in part, at the level of transcription of the Slc23a2 gene and may involve epigenetic mechanism(s).

  19. Chronic binge alcohol exposure during pregnancy impairs rat maternal uterine vascular function.

    Science.gov (United States)

    Subramanian, Kaviarasan; Naik, Vishal D; Sathishkumar, Kunju; Yallampalli, Chandrashekar; Saade, George R; Hankins, Gary D; Ramadoss, Jayanth

    2014-07-01

    Alcohol exposure during pregnancy results in an array of structural and functional abnormalities called fetal alcohol spectrum disorders (FASD). Alcohol dysregulates the exquisite coordination and regulation of gestational adaptations at the level of the uterine vasculature. We herein hypothesized that chronic binge-like alcohol results in uterine vascular dysfunction and impairs maternal uterine artery reactivity to vasoconstrictors and dilators. We utilized a once-daily binge alcohol (4.5 g/kg body weight) exposure paradigm (gestational day 7 to 17) in a pregnant rat model system and investigated primary uterine artery function in response to vasoconstrictors and vasodilators utilizing wire myography. Alcohol (peak blood alcohol concentration, 216 mg/dl) produced uterine vascular dysfunction. Alcohol did not produce altered uterine vascular reactivity to α1 adrenergic agonist phenylephrine or the prostanoid thromboxane. However, alcohol specifically impaired acetylcholine (ACh)-mediated uterine artery vasodilation but exogenous endothelium-independent vasodilators like sodium nitroprusside exhibited no alcohol effect; ACh significantly decreased vessel relaxation (p = 0.003; ↓pD2 [negative log molar ACh concentration producing the half maximum response], -7.004 ± 0.215 vs. -6.310 ± 0.208; EMax [maximal ACh response], 92% vs. 75%). We conclude that moderate alcohol exposure impairs uterine vascular function in pregnant mothers. Alcohol specifically impairs agonist-induced uterine artery vasodilation. In summary, the maternal uterine compartment may play a significant role in the pathogenesis of FASD. Thus, the mechanistic targets of alcohol at the level of both the mother and the fetus need to be considered in order to develop effective therapeutic treatment strategies for FASD. Copyright © 2014 by the Research Society on Alcoholism.

  20. Characterization of Mouse Models of Early Pancreatic Lesions Induced by Alcohol and Chronic Pancreatitis.

    Science.gov (United States)

    Xu, Shiping; Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Bourhim, Mouloud; Grippo, Paul J; Principe, Daniel R; Mascariñas, Emman; DeCant, Brian; Tsukamoto, Hidekazu; Pandol, Stephen J; Edderkaoui, Mouad

    2015-08-01

    We describe the first mouse model of pancreatic intraepithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. Pdx1-Cre;LSL-K-ras mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. The PanIN lesions and markers of fibrosis, inflammation, histone deacetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immunohistochemistry and Western. Exposure of Pdx1-Cre;LSL-K-ras mice to an alcohol diet significantly stimulated fibrosis and slightly but not significantly increased the level of PanIN lesions associated with an increase in tumor-promoting M2 macrophages. Importantly, the alcohol diet did not increase activation of stellate cells. Alcohol diet and cerulein injections resulted in synergistic and additive effects on PanIN lesion and M2 macrophage phenotype induction, respectively. Cerulein pancreatitis caused stellate cell activation, EMT, and cancer stemness in the pancreas. Pancreatitis caused histone deacetylation, which was promoted by the alcohol diet. Pancreatitis increased EMT and cancer stemness markers, which were not further affected by the alcohol diet. The results suggest that alcohol has independent effects on promotion of PDAC associated with fibrosis formed through a stellate cell-independent mechanism and that it further promotes early PDAC and M2 macrophage induction in the context of chronic pancreatitis.

  1. Characterization of mouse models of early pancreatic lesions induced by alcohol and chronic pancreatitis

    Science.gov (United States)

    Xu, Shiping; Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Bourhim, Mouloud; Grippo, Paul J.; Principe, Daniel R.; Mascariñas, Emman; DeCant, Brian; Tsukamoto, Hidekazu; Pandol, Stephen J.; Edderkaoui, Mouad

    2015-01-01

    Objective We describe the first mouse model of pancreatic intra-epithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. Methods Pdx1-Cre; LSL-Kras (KC) mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. PanIN lesions and markers of fibrosis, inflammation, histone de-acetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immuno-histochemistry and Western. Results Exposure of KC mice to an alcohol diet significantly stimulated fibrosis and slightly, but not significantly, increased the level of PanIN lesions associated with an increase in tumor-promoting M2-macrophages. Importantly, the alcohol diet did not increase activation of stellate cells. Alcohol diet and cerulein injections resulted in synergistic and additive effects on PanIN lesion and M2-Macrophage phenotype induction, respectively. Cerulein-pancreatitis caused stellate cell activation, EMT, and cancer stemness in the pancreas. Pancreatitis caused histone deacetylation which was promoted by the alcohol diet. Pancreatitis increased EMT and cancer stemness markers which not further affected by the alcohol diet. Conclusion The results suggest that alcohol has independent effects on promotion of PDAC associated with fibrosis formed through a stellate cell-independent mechanism and that it further promotes early PDAC and M2 macrophage induction in the context of chronic pancreatitis. PMID:26166469

  2. Cerebrospinal fluid monocyte chemoattractant protein-1 in alcoholics: support for a neuroinflammatory model of chronic alcoholism.

    Science.gov (United States)

    Umhau, John C; Schwandt, Melanie; Solomon, Matthew G; Yuan, Peixiong; Nugent, Allison; Zarate, Carlos A; Drevets, Wayne C; Hall, Samuel D; George, David T; Heilig, Markus

    2014-05-01

    Liver inflammation in alcoholism has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) elevations have been noted in the alcoholic brain at autopsy and may have a role in this process. We studied cerebrospinal fluid (CSF) levels of MCP-1 as well as interleukin-1β and tumor necrosis factor-α in 13 healthy volunteers and 28 alcoholics during weeks 1 and 4 following detoxification. Serum liver enzymes were obtained as markers of alcohol-related liver inflammation. Compared to healthy volunteers, MCP-1 levels were significantly higher in alcoholics both on day 4 and day 25 (p alcohol-induced liver inflammation, as defined by peripheral concentrations of GGT and AST/GOT. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  3. Narcolepsy induced by chronic heavy alcohol consumption: a case report

    National Research Council Canada - National Science Library

    Wang, Xinyuan

    2012-01-01

    Narcolepsy is a chronic neurological disorder, characterized by uncontrollable excessive daytime sleepiness, cataplectic episodes, sleep paralysis, hypnagogic hallucinations, and night time sleep disruption...

  4. Hypertrophy signaling pathways in experimental chronic aortic regurgitation

    DEFF Research Database (Denmark)

    Olsen, Niels Thue; Dimaano, Veronica L; Fritz-Hansen, Thomas

    2013-01-01

    at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern......The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one...... of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy....

  5. Synaptic microRNAs Coordinately Regulate Synaptic mRNAs: Perturbation by Chronic Alcohol Consumption.

    Science.gov (United States)

    Most, Dana; Leiter, Courtney; Blednov, Yuri A; Harris, R Adron; Mayfield, R Dayne

    2016-01-01

    Local translation of mRNAs in the synapse has a major role in synaptic structure and function. Chronic alcohol use causes persistent changes in synaptic mRNA expression, possibly mediated by microRNAs localized in the synapse. We profiled the transcriptome of synaptoneurosomes (SN) obtained from the amygdala of mice that consumed 20% ethanol (alcohol) in a 30-day continuous two-bottle choice test to identify the microRNAs that target alcohol-induced mRNAs. SN are membrane vesicles containing pre- and post-synaptic compartments of neurons and astroglia and are a unique model for studying the synaptic transcriptome. We previously showed that chronic alcohol regulates mRNA expression in a coordinated manner. Here, we examine microRNAs and mRNAs from the same samples to define alcohol-responsive synaptic microRNAs and their predicted interactions with targeted mRNAs. The aim of the study was to identify the microRNA-mRNA synaptic interactions that are altered by alcohol. This was accomplished by comparing the effect of alcohol in SN and total homogenate preparations from the same samples. We used a combination of unbiased bioinformatic methods (differential expression, correlation, co-expression, microRNA-mRNA target prediction, co-targeting, and cell type-specific analyses) to identify key alcohol-sensitive microRNAs. Prediction analysis showed that a subset of alcohol-responsive microRNAs was predicted to target many alcohol-responsive mRNAs, providing a bidirectional analysis for identifying microRNA-mRNA interactions. We found microRNAs and mRNAs with overlapping patterns of expression that correlated with alcohol consumption. Cell type-specific analysis revealed that a significant number of alcohol-responsive mRNAs and microRNAs were unique to glutamate neurons and were predicted to target each other. Chronic alcohol consumption appears to perturb the coordinated microRNA regulation of mRNAs in SN, a mechanism that may explain the aberrations in synaptic

  6. The Experimental Manipulation of Desire Thinking in Alcohol use Disorder.

    Science.gov (United States)

    Caselli, Gabriele; Gemelli, Antonella; Spada, Marcantonio M

    2017-03-01

    Desire thinking is a voluntary cognitive process involving verbal and imaginal elaboration of a desired target. Recent research has revealed that desire thinking may play a significant role in the escalation of craving. The goal of this study was to explore the effect of a desire thinking induction on craving in a sample of patients with alcohol use disorder. Ten patients with alcohol use disorder were exposed to a brief exposure to alcohol-related thoughts plus desire thinking induction versus brief exposure to alcohol-related thoughts plus distraction. The induction of desire thinking led to a significant increase in distress and urge to use alcohol when compared to a behavioural assessment test and a distraction task. The clinical implications for the treatment of alcohol use disorder are discussed. Copyright © 2016 John Wiley & Sons, Ltd. Psychotherapeutic strategies that target desire thinking, both at the assessment and at the intervention levels, may be relevant in the treatment of craving-related problems. Deriving and illustrating the role of desire thinking in a given episode of craving may support the development of metacognitive awareness about its functions and consequences. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Reactivity to alcohol assessment measures: an experimental test.

    Science.gov (United States)

    Walters, Scott T; Vader, Amanda M; Harris, T Robert; Jouriles, Ernest N

    2009-08-01

    Previous research has suggested that alcohol screening and assessment may affect drinking. This study was a randomized test of reactivity to alcohol assessment questionnaires among a group of heavy drinking college students. A total of 147 university students completed a screening questionnaire and were randomized to either immediate assessment or delayed assessment. The immediate assessment group completed a set of drinking questionnaires at baseline, 3, 6 and 12 months, while the delayed assessment group completed questionnaires only at 12 months. Primary outcomes included overall volume of drinking, risky drinking and use of risk reduction behaviors. We found a significant effect of assessment on measures of risky drinking and risk reduction behaviors, but not on overall volume of drinking. Specifically, at 12 months, participants who had previously completed drinking assessments had a lower peak blood alcohol concentration (BAC) (d = -0.373), were more likely to report a low score on the Alcohol Use Disorders Identification Test (AUDIT; odds ratio = 2.55) and tended to use more strategies to moderate their alcohol consumption (d = 0.352). Risk reduction behaviors that were affected tended to be those that limited alcohol consumption, rather than those that minimized consequences. These results may have implications for the development of brief interventions.

  8. Portable Chronic Alcohol Consumption Monitor in Human Sweat through Square-Wave Voltammetry.

    Science.gov (United States)

    Kinnamon, David; Muthukumar, Sriram; Panneer Selvam, Anjan; Prasad, Shalini

    2017-09-01

    Chronic alcohol consumption is a significant financial and physical burden in the United States each year. Alcohol consumption monitors focus on establishing a state of intoxication, not assessing a user's health risks as a function of consumed alcohol. This work demonstrates a biosensor for a chronic alcohol consumption monitor through the electrochemical detection of ethyl glucuronide (EtG) in human sweat using square-wave voltammetry (SWV). A novel affinity assay was demonstrated in which monoclonal antibodies were chemically coabsorbed onto a gold electrode surface in parallel with thiolated charge transfer molecule. Concentration-dependent EtG binding was detected by measuring a reduction in the charge transfer of the sensor, manifesting as a current response during SWV measurement. A companion compact electronic reader was constructed, demonstrating comparable sensitivity to a conventional lab instrument. Both tools demonstrated a limit of detection of 0.1 µg/L and a linear dynamic range of 0.1-100 µg/L corresponding to the physiologically relevant range of EtG expression in human sweat. This device can address the need for a chronic alcohol consumption monitor toward establishing a user's long-term consumption habits to assess the risk of developing specific diseases and conditions associated with regular alcohol consumption, through integration with existing technologies.

  9. Hepatic Hazard Assessment of Silver Nanoparticle Exposure in Healthy and Chronically Alcohol Fed Mice

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Jacobsen, Nicklas R.; Roursgaard, Martin

    2017-01-01

    Silver (Ag) nanoparticles (NPs) are currently among one of the most widely used nanomaterials. This in turn, implies an increased risk of human and environmental exposure. Alcohol abuse is a global issue with millions of people in the general population affected by the associated adverse effects....... The excessive consumption of alcohol is a prominent cause of chronic liver disease which manifest in multiple disorders. In this study, the adverse health effects of Ag NP exposure were investigated in models of alcoholic hepatic disease in vitro and in vivo. The data showed that Ag NP induced hepatic health...... effects were aggravated in the alcohol pretreated mice in comparison to controls with regards to an organ specific inflammatory response, changes in blood biochemistry, acute phase response and hepatic pathology. In addition, alcoholic disease influenced the organ’s ability for recovery post-NP challenge...

  10. [The efficacy of enterosorbents and antioxidants in the treatment of chronic liver diseases of alcoholic etiology].

    Science.gov (United States)

    Skalyga, I M; Zhigarenko, N I

    1998-01-01

    Efficacies were studied of enterosorbents (ES) and antioxidants (AO) combined in treatment of chronic hepatic pathology of alcoholic etiology. 102 patients were given ES (enterosgel, polysorb, sillard) in combination with tocopheroli acetas over 6 to 10 days. The control group comprised 84 individuals. A positive effect was ascertained of an ES + AO combination on the clinical course of the illness and on the immunological indices, which observation warrants the above drugs to be included into a combined treatment of patients presenting with chronic disorders of the liver of alcoholic etiology.

  11. Musculus gastrocnemius tetanus kinetics in alcohol-intoxicated rats with experimentally-induced hindlimb vascular ischemia under conditions of low-frequence muscle fatigue

    Directory of Open Access Journals (Sweden)

    O. A. Melnychuk

    2014-04-01

    Full Text Available Alcohol intoxication and ischemic injury of skeletal muscles often accompany each other. It is shown that patients hospitalized with chronic alcoholism develop muscle fatigue. Skeletal muscle dysfunction in alcohol-dependent patients is caused by ethanol-associated myofibrillar atrophy and metabolic disbalance, while compression-ischemic lesions result from unconsciousness of the patient, in case of taking the critical alcohol dose. Therefore, the aim of this study is to discover typical m. gastrocnemius (cap. med. tetanic kinetics changes in alcohol intoxicated rats with experimentally induced vascular ischemia of hindlimb muscles under conditions of low-frequency progressive muscle fatigue. Experiments were carried out on 10 young male Wistar rats (149.5 ± 5.8 g kept under standard vivarium conditions and diet. The investigation was conducted in two phases: chronic (30 days and acute (3 hours experiment. All surgical procedures were carried out aseptically under general anesthesia. Ishemic m. gastrocnemius (cap. med. tetanic kinetic changes and force productivity in alcohol intoxicated rats were investigated in the isometric mode, with direct electrical stimulation. The fatigue of m. gastrocnemius (cap. med. was evaluated by three characteristic criteria: the first sag effect, the secondary force rise, the second sag effect. There have been 10 similar experiments: 5 series in each study group with 10 tetanic runs in each series. The highest amplitude of the native m. gastrocnemius (cap. med. tetanus relative to isoline was taken as 100% force response. The same pattern of m. gastrocnemius (cap. med. low-frequency fatigue development was found in both rat groups under study. It is evidenced by the absence of substantial m. gastrocnemius (cap. med. tetanus kinetics differences in alcohol intoxicated rats, compared with non-alcohol intoxicated rats during fatigue test. However, the appreciable m. gastrocnemius (cap. med. tetanic force reduction

  12. Effect of chronic alcohol ingestion on the progression of periodontitis induced in Fisher-344 rats

    Directory of Open Access Journals (Sweden)

    Éder Ricardo Biasoli

    2009-01-01

    Full Text Available Objective: Understand the effect of chronic alcohol on the progression of periodontitis induced in Fischer-344 rats.Methods: For the study, 22 Fischer-344 rats, two months old were used, divided into groups: alcohol (n=8, ligature (n=7 and control (n=7. On the first day, the animals in the alcohol group were exposed to ingestion of a water solution containing 20% alcohol (size/size, up to day 90. After thirty days from the beginning of the experiment, the animals in the alcohol group and the ligature group were submitted to the placement of a silk thread around the right maxillary second molar. Nothing was performed on the left side, serving as control. All the groups were submitted to euthanasia 60 days after ligature placement. To assess the destruction of periodontitis, a radiographic exam was used to measure the destruction of bone height. Results: The results of the study showed that on the side in which periodontitis was induced, the group that ingested alcohol suffered an increase in destruction, with statistical differences when compared with the ligature and control groups and increased bone destruction in the ligature group when compared to control. Conclusion: Within the limitations of the study, it was concluded that chronic alcohol consumption by Fischer-344 rats led to greater progression of induced periodontitis.

  13. Alcoholic Liver Disease in the Asian–Pacific Region with High Prevalence of Chronic Viral Hepatitis

    Directory of Open Access Journals (Sweden)

    Sien-Sing Yang

    2016-09-01

    Full Text Available The hospitalized cases and mortality from alcoholic liver disease (ALD are increasing in Taiwan and worldwide. Meanwhile, the Asia–Pacific region also has a high prevalence of hepatitis B virus (HBV and hepatocellular carcinoma (HCC. The Taiwanese have the highest percentage of aldehyde dehydrogenase 2 (ALDH2 deficiency and the lowest amount of alcohol consumption. Based on the histological changes, ALD is clinically classified as steatosis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatitis on cirrhosis. Patients with overt alcoholic hepatitis often develop marked hepatomegaly, audible hepatic arterial bruit, mild leukocytosis, and mild fever. Patients having alcoholic cirrhosis had much more serious complications and mortality. It is clinically important to identify hepatic fibrosis and cirrhosis earlier for early management. Active assessments for esophageal varices and ascites may help the diagnosis of cirrhosis. Sonography is helpful for exanimating features of cirrhosis including portal hypertension, ascites, increased hepatic portal flow, and collaterals. Synergistic damage of viral hepatitis on ALD patients lead to rapid progression to cirrhosis and HCC. Distinct from the Western population, 30% of Taiwanese alcoholics had concomitant chronic HBV regardless of the different histologic categories. Patient groups with combined alcoholics and HBV had fewer platelet counts and much more cirrhosis with Ishak Stage 5–6 fibrosis. The annual incidences of HCC were significantly higher in alcoholic cirrhotic patients having concomitant HBV infection than those with only HBV infection or alcoholism alone. Antiviral nucleotide and nucleoside analogs therapy reduces the prevalence of HCC to a similar level to those ALD patients without active HBV.

  14. THE ROLE OF CORTISOL IN CHRONIC BINGE ALCOHOL-INDUCED CEREBELLAR INJURY: OVINE MODEL

    Science.gov (United States)

    Washburn, Shannon E.; Tress, Ursula; Lunde, Emilie R.; Chen, Wei-Jung A.; Cudd, Timothy A.

    2012-01-01

    Women who drink alcohol during pregnancy are at high risk of giving birth to children with neurodevelopmental disorders. Previous reports from our laboratory have shown that third trimester equivalent binge alcohol exposure at a dose of 1.75 g/kg/day results in significant fetal cerebellar Purkinje cell loss in fetal sheep and that both maternal and fetal adrenocorticotropin (ACTH) and cortisol levels are elevated in response to alcohol treatment. In this study, we hypothesized that repeated elevations in cortisol from chronic binge alcohol are responsible at least in part for fetal neuronal deficits. Animals were divided into four treatment groups: normal control, pair-fed saline control, alcohol and cortisol. The magnitude of elevation in cortisol in response to alcohol was mimicked in the cortisol group by infusing pregnant ewes with hydrocortisone for 6 hours on each day of the experiment, and administering saline during the first hour in lieu of alcohol. The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109 until GD 132. Peak maternal blood alcohol concentration in the alcohol group was 239 ± 7 mg/dl. The fetal brains were collected and processed for stereological cell counting on GD 133. The estimated total number of fetal cerebellar Purkinje cells, the reference volume and the Purkinje cell density were not altered in response to glucocorticoid infusion in the absence of alcohol. These results suggest that glucocorticoids independently during the third trimester equivalent may not produce fetal cerebellar Purkinje cell loss. However, the elevations in cortisol along with other changes induced by alcohol could together lead to brain injury seen in the fetal alcohol spectrum disorders. PMID:23218665

  15. Uniting Epidemiology and Experimental Disease Models for Alcohol-Related Pancreatic Disease

    OpenAIRE

    Setiawan, Veronica Wendy; Monroe, Kristine; Lugea, Aurelia; Yadav, Dhiraj; Pandol, Stephen

    2017-01-01

    Findings from epidemiologic studies and research with experimental animal models provide insights into alcohol-related disease pathogeneses. Epidemiologic data indicate that heavy drinking and smoking are associated with high rates of pancreatic disease. Less clear is the association between lower levels of drinking and pancreatitis. Intriguingly, a very low percentage of drinkers develop clinical pancreatitis. Experimental models demonstrate that alcohol administration alone does not initiat...

  16. A common variant of PNPLA3 (p.I148M) is not associated with alcoholic chronic pancreatitis.

    NARCIS (Netherlands)

    Rosendahl, J.; Tonjes, A.; Schleinitz, D.; Kovacs, P.; Wiegand, J.; Ruffert, C.; Jesinghaus, M.; Schober, R.; Herms, M.; Grutzmann, R.; Schulz, H.U.; Stickel, F.; Werner, J.; Bugert, P.; Bluher, M.; Stumvoll, M.; Bohm, S.; Berg, T. van den; Wittenburg, H.; Mossner, J.; Morsche, R.H.M. te; Derikx, M.; Keim, V.; Witt, H.; Drenth, J.P.H.

    2012-01-01

    BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease that in some patients leads to exocrine and endocrine dysfunction. In industrialized countries the most common aetiology is chronic alcohol abuse. Descriptions of associated genetic alterations in alcoholic CP are rare. However, a

  17. [Content of free radical oxidation products in the heart and plasma in diabetes mellitus with concurrent chronic alcohol intoxication].

    Science.gov (United States)

    Indutnyĭ, A V; Bykov, D E; Vysokogorskiĭ, V E

    2010-01-01

    The research results of level glycemia, contents of free radical oxidation products (thiobarbiturate-reactive substances, oxidized-modified proteins) in blood plasma and heart of diabetes mellitus rats with chronic alcohol intoxication are presented. It is shown, that at presence of a diabetes mellitus the chronic alcohol consumption does not change blood plasma levels of the oxidized-modified proteins, thiobarbiturate-reactive substances and glucose. However the contents of thiobarbiturate-reactive substances and oxidizing modification of proteins products in animals heart is more considerably increased at combination of the diabetes with chronic alcohol consumption, in comparison with changes at the diabetes mellitus outside of alcoholization and with changes at the isolated chronic alcohol influence. Found out alcohol-induced free radical processes hyperactivation in heart at the diabetes is capable to render additional injuring influence.

  18. Chronic ethanol consumption increases dopamine uptake in the nucleus accumbens of high alcohol drinking rats

    OpenAIRE

    Carroll, Michelle R.; Rodd, Zachary A.; Murphy, James M.; Simon, Jay R.

    2006-01-01

    Past research has indicated that chronic ethanol exposure enhances dopamine (DA) neurotransmission in several brain regions. The present study examined the effects of chronic ethanol drinking on dopamine transporter (DAT) function in the nucleus accumbens (Acb) of High-Alcohol-Drinking replicate line 1 (HAD-1) rats. HAD rats were given concurrent 24-hr access to 15% ethanol and water or water alone for 8 weeks. Subsequently, DA uptake and the Vmax of the DAT were compared between the two grou...

  19. Posttraumatic immune modulation in chronic alcoholics is associated with multiple organ dysfunction syndrome.

    Science.gov (United States)

    von Heymann, Christian; Langenkamp, Jörg; Dubisz, Norman; von Dossow, Vera; Schaffartzik, Walter; Kern, Hartmut; Kox, Wolfgang J; Spies, Claudia

    2002-01-01

    Patients with chronic alcohol abuse constitute approximately 50% of trauma care patients, and these patients have a two- to fourfold increase in posttraumatic infectious complications. Cytokines such as interleukin-6 (IL-6) and interleukin-10 (IL-10) and the adhesion molecule soluble endothelial selectin (sE-selectin) have been found to play an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome (MODS). The aim of this study was to compare the immune modulation and clinical relevance between chronic alcoholic and nonalcoholic patients following trauma. Sixty-three patients (37 alcohol abusers, 26 nonalcoholics) were included in this prospective controlled study. IL-6, IL-10, and sE-selectin were determined on admission and on days 2, 4, and 7 following admission to the ICU. On admission to the ICU but not on the following days of the study period, plasma IL-6, IL-10, and sE-selectin were significantly elevated in chronic alcoholic patients compared with nonalcoholics. The incidence of MODS was significantly higher in chronic alcoholic patients (89% vs. 50%, p < 0.01), whereas the incidence of pneumonia (35% vs. 19%, p < 0.17) and sepsis (14% vs. 0%, p < 0.07) did not reach statistical significance. The significantly elevated levels of IL-6, IL-10, and sE-selectin in chronic alcoholic trauma patients on admission to the ICU could play an important role in the development of MODS in intensive care. In patients with high levels of inflammatory mediators, immune modulatory treatment before the development of MODS may be considered.

  20. Health risks of chronic moderate and heavy alcohol consumption: how much is too much?

    Science.gov (United States)

    Meyerhoff, Dieter J; Bode, Christiane; Nixon, Sara Jo; de Bruin, Eveline A; Bode, J Christian; Seitz, Helmut K

    2005-07-01

    This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October 2004. Most of what we know about the deleterious effects of alcohol in vivo has been gleaned from studies in sober alcoholics recruited from substance abuse treatment programs. Little is known about effects of chronic drinking in the moderate or heavy range encountered in a much larger fraction of modern society. Extrapolation of information on the adverse effects of chronic drinking on organ function from clinical samples to social drinkers in the general population has to be met with great skepticism, as it may lead to wrong conclusions about the chronic effects of alcohol in social drinkers. Several recent studies suggest that moderate alcohol consumption has certain beneficial health effects, whereas heavy social alcohol consumption has recently been associated with organ abnormalities and cognitive deficits. These social drinking effects have attracted great public interest; reports of benefits of moderate drinking have also inspired inappropriate publications by the media, including misleading advertisements by the alcohol producing and distributing industry. Although adverse effects of moderate to heavy drinking on heart, liver, and cancer development have attracted attention by clinicians and researchers for some time, its compromising effects on brain and cognition have only recently been studied. This symposium brought together researchers from different disciplines, who reviewed and presented new data on consequences of social drinking in the areas of clinical neuropsychology and behavior (Drs. Nixon and Meyerhoff), neurophysiology (Dr. Nixon, Ms. De Bruin), neuroimaging (Ms. de Bruin, Dr. Meyerhoff), hepatic disease (Dr. Bode), and cancer (Dr. Seitz). The symposium aimed to clarify both the potential health benefits of moderate alcohol consumption and risks of moderate and

  1. Uniting Epidemiology and Experimental Disease Models for Alcohol-Related Pancreatic Disease

    Science.gov (United States)

    Setiawan, Veronica Wendy; Monroe, Kristine; Lugea, Aurelia; Yadav, Dhiraj; Pandol, Stephen

    2017-01-01

    Findings from epidemiologic studies and research with experimental animal models provide insights into alcohol-related disease pathogeneses. Epidemiologic data indicate that heavy drinking and smoking are associated with high rates of pancreatic disease. Less clear is the association between lower levels of drinking and pancreatitis. Intriguingly, a very low percentage of drinkers develop clinical pancreatitis. Experimental models demonstrate that alcohol administration alone does not initiate pancreatitis but does sensitize the pancreas to disease. Understanding the effects of alcohol use on the pancreas may prove beneficial in the prevention of both pancreatitis and pancreatic cancer. PMID:28988572

  2. Uniting Epidemiology and Experimental Disease Models for Alcohol-Related Pancreatic Disease.

    Science.gov (United States)

    Setiawan, Veronica Wendy; Monroe, Kristine; Lugea, Aurelia; Yadav, Dhiraj; Pandol, Stephen

    2017-01-01

    Findings from epidemiologic studies and research with experimental animal models provide insights into alcohol-related disease pathogeneses. Epidemiologic data indicate that heavy drinking and smoking are associated with high rates of pancreatic disease. Less clear is the association between lower levels of drinking and pancreatitis. Intriguingly, a very low percentage of drinkers develop clinical pancreatitis. Experimental models demonstrate that alcohol administration alone does not initiate pancreatitis but does sensitize the pancreas to disease. Understanding the effects of alcohol use on the pancreas may prove beneficial in the prevention of both pancreatitis and pancreatic cancer.

  3. Effect of a high-fat diet and alcohol on cutaneous repair: A systematic review of murine experimental models.

    Directory of Open Access Journals (Sweden)

    Daiane Figueiredo Rosa

    Full Text Available Chronic alcohol intake associated with an inappropriate diet can cause lesions in multiple organs and tissues and complicate the tissue repair process. In a systematic review, we analyzed the relevance of alcohol and high fat consumption to cutaneous and repair, compared the main methodologies used and the most important parameters tested. Preclinical investigations with murine models were assessed to analyze whether the current evidence support clinical trials.The studies were selected from MEDLINE/PubMed and Scopus databases, according to Fig 1. All 15 identified articles had their data extracted. The reporting bias was investigated according to the ARRIVE (Animal Research: Reporting of in Vivo Experiments strategy.In general, animals offered a high-fat diet and alcohol showed decreased cutaneous wound closure, delayed skin contraction, chronic inflammation and incomplete re-epithelialization.In further studies, standardized experimental design is needed to establish comparable study groups and advance the overall knowledge background, facilitating data translatability from animal models to human clinical conditions.

  4. Testing the validity of the Danish urban myth that alcohol can be absorbed through feet: open labelled self experimental study

    Science.gov (United States)

    Hansen, Christian Stevns; Færch, Louise Holmsgaard

    2010-01-01

    Objective To determine the validity of the Danish urban myth that it is possible to get drunk by submerging feet in alcohol. Design Open labelled, self experimental study, with no control group. Setting Office of a Danish hospital. Participants Three adults, median age 32 (range 31-35), free of chronic skin and liver disease and non-dependent on alcohol and psychoactive drugs. Main outcome measures The primary end point was the concentration of plasma ethanol (detection limit 2.2 mmol/L (10 mg/100 mL)), measured every 30 minutes for three hours while feet were submerged in a washing-up bowl containing the contents of three 700 mL bottles of vodka. The secondary outcome was self assessment of intoxication related symptoms (self confidence, urge to speak, and number of spontaneous hugs), scored on a scale of 0 to 10. Results Plasma ethanol concentrations were below the detection limit of 2.2 mmol/L (10 mg/100 mL) throughout the experiment. No significant changes were observed in the intoxication related symptoms, although self confidence and urge to speak increased slightly at the start of the study, probably due to the setup. Conclusion Our results suggest that feet are impenetrable to the alcohol component of vodka. We therefore conclude that the Danish urban myth of being able to get drunk by submerging feet in alcoholic beverages is just that; a myth. The implications of the study are many though. PMID:21156749

  5. Hyperhomocysteinemia in chronic alcoholism: A case with retinal manifestations.

    Science.gov (United States)

    Palmero-Fernández, L; Fernández-Treguerres, F; Santos-Bueso, E; Sáenz-Francés, F; Martínez-de-la-Casa, J M; García-Feijóo, J; García-Sánchez, J

    2014-08-01

    An alcoholic patient with loss of vision in his right eye and a peripapillar haemorrhage, who then presented with a venous thrombosis. Blood analysis revealed hyperhomocysteinemia with coagulation parameters within the normal range. In the follow-up he developed a bilateral optic neuropathy. An increase in homocysteine levels is common in alcoholics, and it has been considered a vascular risk factor. Folic acid and vitamins B6 and B12 deficiency may lead to hyperhomocysteinemia, as they participate in its metabolism. When presented with a retinal occlusive disease or ischemic optic neuropathy in young patients, coagulation disorders and elevated levels of homocysteine should be ruled out. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. Acute and chronic effects of dinner with alcoholic beverages on nitric oxide metabolites in healthy men

    NARCIS (Netherlands)

    Sierksma, A.; Gaag, M.S. van der; Grobbee, D.E.; Hendriks, H.F.J.

    2003-01-01

    1. The present study investigated the acute and chronic effect of dinner with alcoholic beverages on serum nitric oxide (NO) metabolites, namely nitrate and nitrite (NOx), in 11 healthy, non-smoking middle-aged men. 2. In a randomized, diet-controlled, cross-over trial, subjects consumed dinner with

  7. The effects of chronic alcohol self-administration in nonhuman primate brain networks.

    Science.gov (United States)

    Telesford, Qawi K; Laurienti, Paul J; Davenport, April T; Friedman, David P; Kraft, Robert A; Daunais, James B

    2015-04-01

    Long-term alcohol abuse is associated with change in behavior, brain structure, and brain function. However, the nature of these changes is not well understood. In this study, we used network science to analyze a nonhuman primate model of ethanol self-administration to evaluate functional differences between animals with chronic alcohol use and animals with no exposure to alcohol. Of particular interest was how chronic alcohol exposure may affect the resting state network. Baseline resting state functional magnetic resonance imaging was acquired in a cohort of vervet monkeys. Animals underwent an induction period where they were exposed to an isocaloric maltose dextrin solution (control) or ethanol in escalating doses over three 30-day epochs. Following induction, animals were given ad libitum access to water and a maltose dextrin solution (control) or water and ethanol for 22 h/d over 12 months. Cross-sectional analyses examined region of interests in hubs and community structure across animals to determine differences between drinking and nondrinking animals after the 12-month free access period. Animals were classified as lighter (Animals that consume alcohol show topological differences in brain network organization, particularly in animals that drink heavily. Differences in the resting state network were linked to areas that are associated with spatial association, working memory, and visuomotor processing. Copyright © 2015 by the Research Society on Alcoholism.

  8. The Effect of Chronic Alcoholism on the Conjunctival Flora.

    Science.gov (United States)

    Gunduz, Göksel; Gunduz, Abuzer; Polat, Nihat; Cumurcu, Birgul Elbozan; Yakupogulları, Yusuf

    2016-06-01

    We aimed to investigate the effect of alcohol abuse on the conjunctival flora. The cases were evaluated as two groups. The study group consisted of 55 heavy-drinking males diagnosed with alcohol abuse, while the control group consisted of 55 males without a history of alcohol abuse. Samples were taken from the inferior fornix conjunctiva with sterile cotton-tipped swabs (Amies transport medium) for culture. The samples were inoculated into blood agar, chocolate agar, eosine methylene blue agar and Saboraud-Dextrose agar (Oxoid/UK) with the dilution method. The microorganisms that grew in study group subjects were Coagulase Negative Staphylococcus (CNS) in 30 (54.5%), Staphylococcus aureus in 14 (25.5%), Moraxella spp. in 3 (5.5%), Streptococcus spp. in 3 (5.5), Bacillus spp. in 3 (5.5%), Corynebacterium spp. in 3 (5.5%), Candida spp. in 3 (5.5%), Haemophilus spp. in 2 (3.6%), Acinetobacter spp. in 2 (3.6%), Neisseria spp. in 1 (1.8%) and Micrococcus spp. in 1 (1.8%). The results for control group were CNS in 31 (56.4%), Bacillus spp. in 7 (12.7%), S. aureus in 5 (9.1%), and Corynebacterium spp. in 2 (3.6%). Moraxella spp., Streptococcus spp., Candida spp., Haemophilus spp., Acinetobacter spp., Neisseria spp. and Micrococcus spp. microorganisms grew in the conjunctival flora samples of the study group but not in the control group. S. aureus colonization was significantly higher in the study group than the control group (p alcoholism is different than the normal population.

  9. Chronic alcohol consumption from adolescence to adulthood in mice--hypothalamic gene expression changes in insulin-signaling pathway.

    Science.gov (United States)

    Wang, Ke; Song, Huaiguang; Jin, Meilei; Xiao, Huasheng; Zhao, Guoping; Zou, Hong; Yu, Lei

    2014-09-01

    Adolescence is a developmental stage vulnerable to alcohol drinking-related problems, and alcohol exposure during adolescence may lead to long-lasting consequences. The hypothalamus is a key brain region for food and water intake regulation as well as weight control, and is one of the alcohol-sensitive brain regions. However, it is not known what the alcohol effect is on the hypothalamus following adolescent alcohol intake, chronically over adolescent development, at moderate levels. We employed a model of chronic moderate alcohol intake from adolescence to adulthood in mice, and analyzed the effect of alcohol on growth and weight gain, as well as hypothalamic gene expression patterns. The results indicated that chronic alcohol consumption during adolescence, even at moderate levels, led to both a reduction in weight gain in mice, and considerable gene expression changes in the hypothalamus. Pathway analysis and real-time PCR identified the type II diabetes mellitus and the insulin-signaling pathways as being the hypothalamic pathways affected by chronic alcohol. Our findings from the mouse alcohol consumption study therefore serve as a potential warning against alcohol consumption during adolescence, such as in teens and college students. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Chronic alcohol ingestion increases mortality and organ injury in a murine model of septic peritonitis.

    Directory of Open Access Journals (Sweden)

    Benyam P Yoseph

    Full Text Available BACKGROUND: Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was to determine how chronic alcohol ingestion alters the host response to sepsis in mice. METHODS: Mice were randomized to receive either alcohol or water for 12 weeks and then subjected to cecal ligation and puncture. Mice were sacrificed 24 hours post-operatively or followed seven days for survival. RESULTS: Septic alcohol-fed mice had a significantly higher mortality than septic water-fed mice (74% vs. 41%, p = 0.01. This was associated with worsened gut integrity in alcohol-fed mice with elevated intestinal epithelial apoptosis, decreased crypt proliferation and shortened villus length. Further, alcohol-fed mice had higher intestinal permeability with decreased ZO-1 and occludin protein expression in the intestinal tight junction. The frequency of splenic and bone marrow CD4+ T cells was similar between groups; however, splenic CD4+ T cells in septic alcohol-fed mice had a marked increase in both TNF and IFN-γ production following ex vivo stimulation. Neither the frequency nor function of CD8+ T cells differed between alcohol-fed and water-fed septic mice. NK cells were decreased in both the spleen and bone marrow of alcohol-fed septic mice. Pulmonary myeloperoxidase levels and BAL levels of G-CSF and TFG-β were higher in alcohol-fed mice. Pancreatic metabolomics demonstrated increased acetate, adenosine, xanthine, acetoacetate, 3-hydroxybutyrate and betaine in alcohol-fed mice and decreased cytidine, uracil, fumarate, creatine phosphate, creatine, and choline. Serum and peritoneal cytokines were generally similar between alcohol-fed and water-fed mice, and there were no differences in bacteremia, lung wet to dry weight, or pulmonary, liver or splenic histology. CONCLUSIONS: When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality

  11. [Neurological complications of chronic alcoholism: study of 42 observations in Guinea].

    Science.gov (United States)

    Cisse, F A; Keita, M M; Diallo, I M; Camara, M I; Konate, M M; Konate, F; Conde, K; Diallo, A N; Nyassinde, J; Djigue, B S; Camara, M; Koumbassa, M L; Diakhate, I; Cisse, A

    2014-01-01

    Neurologic disorders related to chronic alcoholism in traditional areas of Guinea are frequent, but reports about them are rare. We conducted the first study in Guinea on this subject and retrospectively collected 42 cases of neurologic manifestations related to alcoholism over a 7-year period. The standard findings of the literature were confirmed in our population: peak frequency after the age of 40 years (82.8%) and clear male overrepresentation (M/F sex ratio: 13/1). All the standard signs and symptoms are reported, with a clear predominance of alcoholic polyneuropathy and hepatic encephalopathy. The study of nutritional status by both body mass index (BMI) and the Detsky criteria showed that these patients were severely malnourished. The brain MRI was a crucial contribution for diagnosing the standard central nervous system complications of alcoholism: Gayet Wernicke encephalopathy, Marchiafava-Bignami disease, Korsakoff syndrome, central pontine myelinolysis, and cerebellar degeneration.

  12. Interaction of cannabinoid receptor 2 and social environment modulates chronic alcohol consumption.

    Science.gov (United States)

    Pradier, Bruno; Erxlebe, Edda; Markert, Astrid; Rácz, Ildikó

    2015-01-01

    Genetic and environmental factors contribute nearly in equal power to the development of alcoholism. Environmental factors, such as negative life events or emotionally disruptive conditions, initiate and promote alcohol drinking and relapse. The endocannabinoid system is involved in hedonic control and modulates stress reactivity. Furthermore, chronic alcohol drinking alters endocannabinoid signalling, which in turn influences the stress reactivity. Recently, it has been shown that CB2 receptor activity influences stress sensitivity and alcohol drinking. We hypothesized that CB2 receptors influence the impact of environmental risk factors on alcohol preference and consumption. Therefore, in this study, we investigated the alcohol-drinking pattern of wild-type and CB2-deficient animals under single- and group-housing conditions using different alcohol-drinking models, such as forced drinking, intermittent forced drinking and two-bottle choice paradigms. Our data showed that CB2 receptor modulates alcohol consumption and reward. Interestingly, we detected that lack of CB2 receptors led to increased alcohol drinking in the intermittent forced drinking paradigm under group-housing conditions. Furthermore, we found that CB2 knockout mice consumed more food and that their body weight gain was modulated by social environment. On the basis of these data, we conclude that social environment critically affects the modulatory function of CB2 receptors, especially in alcohol intake. These findings suggest that a treatment strategy targeting CB2 receptors may have a beneficial effect on pathological drinking, particularly in situations of social stress and discomfort. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Effect of quality chronic disease management for alcohol and drug dependence on addiction outcomes.

    Science.gov (United States)

    Kim, Theresa W; Saitz, Richard; Cheng, Debbie M; Winter, Michael R; Witas, Julie; Samet, Jeffrey H

    2012-12-01

    We examined the effect of the quality of primary care-based chronic disease management (CDM) for alcohol and/or other drug (AOD) dependence on addiction outcomes. We assessed quality using (1) a visit frequency based measure and (2) a self-reported assessment measuring alignment with the chronic care model. The visit frequency based measure had no significant association with addiction outcomes. The self-reported measure of care-when care was at a CDM clinic-was associated with lower drug addiction severity. The self-reported assessment of care from any healthcare source (CDM clinic or elsewhere) was associated with lower alcohol addiction severity and abstinence. These findings suggest that high quality CDM for AOD dependence may improve addiction outcomes. Quality measures based upon alignment with the chronic care model may better capture features of effective CDM care than a visit frequency measure. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Chronic effects of hydro-alcoholic artemisia absinthium extract on ...

    African Journals Online (AJOL)

    Artemisia absinthium has many pharmacological effects, but toxic effects of it, were seen on nervous system and liver. Therefore, the aim of this study was to evaluate the chronic effects of different doses of Artemisia absinthium extract on the enzymes and histopathological changes of the liver tissue of adult normal male rat.

  15. Intestinal Redox Status of Major Intracellular Thiols in a Rat Model of Chronic Alcohol Consumption

    Science.gov (United States)

    Tian, Junqiang; Brown, Lou Ann S.; Jones, Dean P.; Levin, Marc S.; Wang, Lihua; Rubin, Deborah C.; Ziegler, Thomas R.

    2011-01-01

    Background Alcohol consumption is associated with oxidative stress in multiple tissues in vivo, yet the effect of chronic alcohol intake on intestinal redox state has received little attention. In this study, we investigated the redox status of 2 major intracellular redox regulating couples: glutathione (GSH)/glutathione disulfide (GSSG) and cysteine (Cys)/cystine (CySS) in a rat model of chronic alcohol ingestion. Methods Sprague-Dawley rats were fed the liquid Lieber-DeCarli diet consisting of 36% ethanol of total calories for 6 weeks. Control rats were pair-fed with an isocaloric, ethanol-free liquid diet. Defined mucosal samples from the jejunum, ileum, and colon were obtained and analyzed by high-performance liquid chromatography (HPLC) for GSH and Cys pool redox status. Mucosal free malondialdehyde (MDA) was measured as an indicator of lipid peroxidation. Results In the ethanol-fed rats, Cys and mixed disulfide (GSH-Cys) were significantly decreased in all 3 segments of intestinal mucosa. Free MDA was increased in jejunal but not in ileal or colonic mucosa. Chronic ethanol ingestion significantly increased mucosal GSH concentration in association with a more reducing GSH/GSSG redox potential in the jejunum, but these indices were unchanged in the ileum. In the colon, chronic ethanol ingestion increased oxidant stress as suggested by decreased GSH and oxidized GSH/GSSG redox potential. Conclusions Chronic alcohol intake differentially alters the mucosal redox status in proximal to distal intestinal segments in rats. Such changes may reflect different adaptability of these intestinal segments to the oxidative stress challenge induced by chronic ethanol ingestion. PMID:19597188

  16. Effects of chronic moderate alcohol consumption and novel environment on heart rate variability in primates (Macaca fascicularis).

    Science.gov (United States)

    Shively, Carol A; Mietus, Joseph E; Grant, Kathleen A; Goldberger, Ary L; Bennett, Allyson J; Willard, Stephanie L

    2007-06-01

    The effects of chronic moderate alcohol consumption on cardiac function are not understood. Acute stress may affect cardiac function by shifting autonomic cardiac regulation in favor of the sympathetic nervous system. Although alcohol consumption often increases at times of stress, the interactive effects of stress and chronic moderate alcohol consumption on cardiac regulation have not been studied. The objective was to assess the effects of long-term (1-2 years) moderate (a two-drink/day equivalent, 5 days/week) alcohol consumption on heart rate (HR) variability under normal and acutely stressful conditions in small stable groups of ovariectomized adult cynomolgus monkeys (Macaca fascicularis). Monkeys were trained to voluntarily drink their daily alcohol dose (moderate alcohol consumption decreased HR variability and the low frequency components of the power spectrum. When stressed, monkeys with a history of chronic moderate alcohol consumption had higher HRs than the controls. HR dynamics in monkeys rapidly respond to acute stress. Chronic moderate alcohol consumption may be deleterious to cardiac function. HR response to stress may be exaggerated when accompanied by a history of chronic moderate alcohol consumption.

  17. Alcohol

    Science.gov (United States)

    ... to buy or use alcohol. By setting the drinking age at 21, they hope older people will be ... stop without help. A person who starts drinking alcohol at a young age is more likely to develop alcoholism. Alcoholism is ...

  18. Carnitine: function, metabolism and value in hepatic failure during chronic alcohol intoxication

    Directory of Open Access Journals (Sweden)

    Alina Kępka

    2011-10-01

    Full Text Available Alcoholism is one of the most frequent dependences among people, leading to damage of the liver and death of the person. Chronic alcohol consumption decreases fatty acid oxidation by interfering with carnitine metabolism and citric acid cycle activity. Block in activity of the citric acid cycle caused by alcohol and its metabolites is partially compensated by increased ketone body production, which results in ketosis. Chronic administration of alcohol induces liver injury, inflammation, cirrhosis, focal necrosis and steatosis.L-carnitine (L-3-hydroxy-4-N, N, N-trimethylaminebutyric acid is an essential factor in fatty acid metabolism, which plays a major role in transport of activated long-chain fatty acids to sites of β-oxidation in mitochondria. Carnitine also stabilizes cell membranes by removing long-chain acyl-CoA and excess of the acyl group from the body. L-carnitine can be a useful and safe drug in the liver pathology induced by chronic ethanol exposure.

  19. Severe diffuse axon injury in chronic alcoholic rat medulla oblongata following a concussion blow.

    Science.gov (United States)

    Luo, Jianming; Chen, Guang; Wei, Lai; Qian, Hong; Lai, Xiaoping; Wang, Dian; Lv, Junyao; Yu, Xiaojun

    2014-01-01

    We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined. (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.

  20. Approach to the pharmacological management of chronic pain in patients with an alcohol use disorder

    Directory of Open Access Journals (Sweden)

    Murphy L

    2015-11-01

    Full Text Available Laura Murphy,1,2 Karen WK Ng,1 Victoria CH Su,3 Sarah Woodworth-Giroux,4 Todd S Levy,1 Beth A Sproule,2,5 Andrea D Furlan1,6 1University Health Network, Toronto, ON, Canada; 2Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; 3St Paul's Hospital, Lower Mainland Pharmacy Services, Vancouver, BC, Canada; 4Windsor Regional Hospital, Windsor, ON, Canada; 5Centre for Addiction and Mental Health (CAMH, Toronto, ON, Canada; 6Institute for Work and Health, Toronto, ON, Canada Abstract: This paper provides an overview of research, guidelines, and clinical considerations for the use of medications for chronic pain in the management of patients with an alcohol use disorder. A review of the literature identified randomized controlled trials, epidemiological cohort studies, consensus guidelines, and one systematic review and meta-analysis. Where gaps in the literature existed, clinical experience of the authors is included. Use of nonopioid medications should be given priority and may offer a more favorable risk profile as well as benefits beyond pain management, such as improvement in anxiety, depression, or insomnia. Pregabalin and gabapentin have additional benefits to decrease alcohol cravings or time to relapse after a period of abstinence from alcohol. Drug interactions between selected analgesics and alcohol, disulfiram, or naltrexone require careful consideration. Keywords: chronic pain, alcohol use disorder, opioids 

  1. Chronic moderate alcohol consumption induces iNOS expression in the penis: An immunohistochemical study.

    Science.gov (United States)

    Gonca, Süheyla; Yazir, Yusufhan; Göçmez, Semil Selcan; Dalçik, Ekim Nur; Utkan, Tijen; Dalçik, Hakki

    2014-01-01

    To investigate the effect of moderate alcohol consumption on metabolic alterations, inducible nitric oxide synthase (iNOS), immunohistochemical distribution, and morphological damage to penile erectile tissue in rats. Male Wistar albino rats were divided into 2 groups. Group 1 rats (control group, n = 8) received tap water ad libitum, and group 2 rats (n = 8) were fed with 20% ethanol. Increasing levels of alcohol were given to the rats over 12 weeks. Immunohistochemistry was then performed using the avidin-biotin-peroxidase technique on 5-pm thickness tissue sections. Stained sections were examined by imaging microscope. Alcohol consumption resulted in a significant increase in iNOS immunoreactivity in the penile erectile tissue. Increased iNOS expression was determined in the tunica albuginea, cavernosal smooth muscle cells, trabeculae of connective tissue, arterioles, and the urethral epithelium. Moreover, chronic alcohol consumption resulted in decreasing serum testosterone and high density lipoprotein (HDL) levels with increasing cholesterol and triglyceride levels. Chronic moderate alcohol consumption can affect penile erectile tissue by increasing iNOS immunoreactivity and induce histopathological damage such as penile fibrosis. These abnormalities are also related to the defense mechanism against morphological damage.

  2. [Relation between expression of cerebral beta-APP in the chronic alcoholism rats and death caused by TSAH].

    Science.gov (United States)

    Wei, Lai; Lei, Huai-Cheng; Yu, Xiao-Jun; Lai, Xiao-Ping; Qian, Hong; Xu, Xiao-Hu; Zhu, Fang-Cheng

    2013-04-01

    By observing the cerebral beta-amyloid precursor protein (beta-APP) expression in the chronic alcoholism rats with slight cerebral injury, to discuss the correlation of chronic alcoholism and death caused by traumatic subarachnoid haemorrhage (TSAH). Sixty male SD rats were randomly divided into watering group, watering group with strike, alcoholism group and alcoholism group with strike. Among them, the alcohol was used for continuous 4 weeks in alcoholism groups and the concussion was made in groups with strike. In each group, HE staining and immunohistochemical staining of the cerebral tissues were done and the results were analyzed by the histopathologic image system. In watering group, there was no abnormal. In watering group with strike, mild neuronic congestion was found. In alcoholism group, vascular texture on cerebral surface was found. And the neurons arranged in disorder with dilated intercellular space. In alcoholism group with strike, diffuse congestion on cerebral surface was found. And there was TSAH with thick-layer patches around brainstem following irregular axonotmesis. The quantity of beta-APP IOD in alcoholism group was significantly higher in the frontal lobe, hippocampus, cerebellum, brainstem than those in watering group with strike and alcoholism group with strike. The cerebral tissues with chronic alcoholism, due to the decreasing tolerance, could cause fatal TSAH and pathological changes in cerebral tissues of rats under slight cerebral injury.

  3. Systematic review: effect of alcohol intake on adherence to outpatient medication regimens for chronic diseases.

    Science.gov (United States)

    Grodensky, Catherine A; Golin, Carol E; Ochtera, Rebecca D; Turner, Barbara J

    2012-11-01

    Nonadherence to medications can lead to adverse health outcomes. Alcohol consumption has been shown to be associated with nonadherence to antiretroviral medications, but this relationship has not been examined at different drinking levels or with other chronic disease medications. We conducted a narrative synthesis of the association of alcohol consumption with nonadherence to medications for four chronic diseases. We searched MEDLINE, PsycINFO, Cochrane Library, and Web of Science for relevant studies published through 2009. To be included in this analysis, studies had to be quantitative; have a sample size of 50 or greater; and examine the effect of alcohol consumption on medication adherence for diabetes, hypertension, depression, or HIV/AIDS. Study characteristics and results were abstracted according to pre-specified criteria, and study quality was assessed. Study heterogeneity prevented a systematic synthesis. Sixty eligible studies addressed medication adherence for HIV in 47 (78%), diabetes in 6 (10%), hypertension in 2 (3%), both diabetes and hypertension in 1 (2%), depression in 2 (3%), and all medications in 2 (3%). Mean number of subjects was 245 (range: 57-61,511). Effect sizes for the association of alcohol use with nonadherence varied (0.76-4.76). Six of the seven highest quality studies reported significant effect sizes (p < .05), ranging from 1.43 to 3.6. Most (67%) studies reporting multivariate analyses, but only half of non-HIV medicine studies, reported significant associations. Most studies reported negative effects of alcohol consumption on adherence, but evidence among non-HIV studies was less consistent. These data suggest the relevance of addressing alcohol use in improving antiretroviral adherence and a need for further rigorous study in non-HIV chronic diseases.

  4. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Schütz, Tanja

    2000-01-01

    and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD). METHODS: The permeability to polyethylene glycol Mr 400......BACKGROUND/AIMS: No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse...... with alcoholic liver disease (20/54, pintestinal barrier, which might enhance...

  5. Microsatellite Scan Identifies New Candidate Genes for Susceptibility to Alcoholic Chronic Pancreatitis in Japanese Patients

    Directory of Open Access Journals (Sweden)

    Kei Kitahara

    2008-01-01

    Full Text Available Alcohol abuse is one of the most common risk factor for chronic pancreatitis, but the underlying pathophysiological mechanisms remain unclear. The aim of this study was to identify genes that contribute to susceptibility or resistance for alcoholic chronic pancreatitis by screening the whole genome. Sixty-five patients with alcoholic chronic pancreatitis (63 men and 2 women, mean age 55.2 years and 99 healthy Japanese controls were enrolled in this study. This was an association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. This search revealed 10 candidate susceptibility regions and 5 candidate resistant regions throughout the genome. No specific microsatellite markers were detected in association with previously reported susceptibility genes for chronic pancreatitis, such as PRSS1, PRSS2, CTRC, SPINK1, CFTR, ALDH2, and CYP2E1. Among the statistically significant markers, D15S1007 on chromosome 15q14 showed strong evidence for disease susceptibility (70.8% vs. 35.1%, Pc = 0.0001. Within 500 kb of D15S1007, several genes were candidate genes for susceptibility, including FMN1, DKFZP686C2281, LOC440268, RYR3, and AVEN, This study identified 10 candidate susceptibility and 5 candidate resistant regions that may contain genes involved in ACP pathogenesis.

  6. [Comparative morphological characteristic of immune deficiency in subjects with opioid addiction and chronic alcoholic intoxication].

    Science.gov (United States)

    Pigolkin, Iu I; Gasanov, A B

    2010-01-01

    The objective of the present study was to analyse changes of morphological properties in the organs of immune and endocrine systems in subjects with opioid addiction and chronic alcoholic intoxication (CAI) based on the results of 322 autopsies. These included 190 cases of drug addiction from 0.5 to 10.5 years in duration, 90 cases of chronic alcoholic intoxication, 42 cases of combined drug addiction and CAI. The study demonstrated phasic character of changes in the organs of immune and endocrine systems in subjects with opioid addiction. Three phases were distinguished in the development of immune and endocrine disorders (secondary immunodeficiency syndrome) that correspond to the stages of formation, compensation, and decompensation, respectively, of general adaptation syndrome as a reaction to chronic stress. These processes may be deranged in case of combination of opioid addiction and CAI when changes in the immune and endocrine systems resemble those observed in severe immunodeficiency with serious atrophic and sclerotic lesions in lymphoid organs and endocrine glands. Characteristics of immune deficiency resulting from the consumption of narcotic substances and chronic alcoholic intoxication have much in common even though either of the two underlying conditions shows certain specific features.

  7. Microsatellite Scan Identifies New Candidate Genes for Susceptibility to Alcoholic Chronic Pancreatitis in Japanese Patients

    Science.gov (United States)

    Kitahara, Kei; Kawa, Shigeyuki; Katsuyama, Yoshihiko; Umemura, Takeji; Ozaki, Yayoi; Takayama, Mari; Arakura, Norikazu; Ota, Masao

    2008-01-01

    Alcohol abuse is one of the most common risk factor for chronic pancreatitis, but the underlying pathophysiological mechanisms remain unclear. The aim of this study was to identify genes that contribute to susceptibility or resistance for alcoholic chronic pancreatitis by screening the whole genome. Sixty-five patients with alcoholic chronic pancreatitis (63 men and 2 women, mean age 55.2 years) and 99 healthy Japanese controls were enrolled in this study. This was an association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. This search revealed 10 candidate susceptibility regions and 5 candidate resistant regions throughout the genome. No specific microsatellite markers were detected in association with previously reported susceptibility genes for chronic pancreatitis, such as PRSS1, PRSS2, CTRC, SPINK1, CFTR, ALDH2, and CYP2E1. Among the statistically significant markers, D15S1007 on chromosome 15q14 showed strong evidence for disease susceptibility (70.8% vs. 35.1%, Pc = 0.0001). Within 500 kb of D15S1007, several genes were candidate genes for susceptibility, including FMN1, DKFZP686C2281, LOC440268, RYR3, and AVEN, This study identified 10 candidate susceptibility and 5 candidate resistant regions that may contain genes involved in ACP pathogenesis. PMID:19096130

  8. Effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment.

    Science.gov (United States)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina; Haldrup, David; Pedersen, Steen Bønløkke; Jessen, Niels; Christensen, Lars Porskjaer; Grønbaek, Henning

    2016-03-01

    Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. Resveratrol (RSV) prevents the development of steatosis in a number of experimental fatty liver (non-alcoholic fatty liver [NAFL]) models, but the preventive or therapeutic effects on experimental NASH are not yet clarified, and clinical results on non-alcoholic fatty liver disease are ambiguous. Thus, we aimed to compare the RSV-mediated preventive and therapeutic effects on experimental NAFL and NASH. We used a high-fat (HF) diet to generate a rat NAFL model and a high-fat, high-cholesterol (HFC) diet to generate a rat NASH model. The preventive and therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from study start or after 1 week of the diets. Animals were sacrificed after 8 weeks with appropriate controls. Blood and liver were harvested for analysis, including measurement of RSV metabolites. Resveratrol reduced the development of histological steatosis (P = 0.03) and partly triglyceride accumulation (fold change reduced from 3.6 to 2.4, P = 0.08) in the male NAFL model, although effects were moderate. In NASH prevention, RSV reduced the accumulation of triglyceride in hepatic tissue (P liver tissue, confirming low bioavailability. These experimental findings suggest that a weak hepatic benefit of RSV treatment is seen in prevention of steatosis only. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  9. EFFECTS OF THE LITHIUM – CONTAINING SORBENT ON TERMS OF BEHAVIORAL REACTIONS UNDER CHRONIC ALCOHOL INTOXICATION MODEL

    Directory of Open Access Journals (Sweden)

    A. A. Kotlyarova

    2016-01-01

    Full Text Available Lithium preparations are widely used for stabilize mood in case of bipolar affective disorder. Currently neuroprotective and neuroregenerative effects of lithium are of interest as in case of acute brain injury, also in chronic neurodegenerative diseases such as dementia, alcoholism, Alzheimer disease, etc. [1–5]. In clinical practice use of lithium preparations is limited due to difficult adjustment of drug dosage, necessity of monitoring its concentration in blood, side effects development as a result of accumulation of lithium in a body. For the purpose of improvement of pharmacologic properties lithium is combined with other agents (for example modifying sorbent thus it can produce longer-term and more harmless (less side reactions effect in the long view. Lithium immobilization on sorption basis will allow to use sorbent as detoxicant and carrying agent of drugs to body. The purpose of the work is studying the effect of the lithium – containing sorbent on terms of behavioral reactions under chronic alcohol intoxication model.Materials and methods. During the work we used nonlinear mice – males, which weight 25–30 g (180 animals. Chronic alcohol intoxication was precipitated via 40% proof spirit injections (oral supplementation in quantity of 3 g/kg during 2 weeks, additionally mice drunk 5% proof spirit from drinking bowl. Each experimental group consisted of 10 animals. Study drugs were inserted inside while ethanol injecting. Control animals were inserted 0,9% salin solution. Emotional state of animals was assessed through forced swim test, short – term memory assessment was performed through conditioned passive avoidance reflex. Effect of chronic alcohol intoxication on the parameters of conditioned reflex activity was measured every 7 days.Results. It was found that the investigated lithium-containing sorbent increases: the number of mice are trained passive avoidance reflex, remembering percent of electric shock

  10. Chronic alcoholism and bone remodeling processes: Caveats and considerations for the forensic anthropologist.

    Science.gov (United States)

    Michael, Amy R; Bengtson, Jennifer D

    2016-02-01

    Clinical literature provides substantial information on the effects of chronic alcohol abuse on bone remodeling and related skeletal disease processes. This biomedical information is seldom considered in detail by forensic anthropologists, who often rely on normative macroscopic models of bone remodeling and traditional macroscopic age estimation methods in the creation of biological profiles. The case study presented here considers the ways that alcoholism disrupts normal bone remodeling processes, thus skewing estimations of age-at-death. Alcoholism affects bone macroscopically, resulting in a porous appearance and an older estimation of age, while simultaneously inhibiting osteoblastic activity and resulting in a younger microscopic appearance. Forensic anthropologists must also be cognizant of pathological remodeling stemming from alcoholism in cases where trauma analysis is critical to the reconstruction of events leading up to death, as fracture healing rates can be affected. Beyond the case study, we also consider how forensic anthropologists and practitioners can recognize and account for osteological signatures of alcoholism in medico-legal contexts. In order to best estimate age at death, a combined macroscopic and microscopic approach should be employed whenever possible alcohol and drug abuse is known or suspected. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  11. Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism.

    Science.gov (United States)

    Fama, Rosemary; Le Berre, Anne-Pascale; Hardcastle, Cheshire; Sassoon, Stephanie A; Pfefferbaum, Adolf; Sullivan, Edith V; Zahr, Natalie M

    2017-12-15

    Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n = 96) and a normal comparison group (n = 41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernicke's encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernicke's encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functioning and oculomotor abnormalities in 86 of the 96 ALC participants. Subgroups based on Caine criteria yielded a graded effect, where those meeting more criteria exhibited greater impairment than those meeting no to fewer criteria. These results could not be accounted for by history of drug dependence. Multiple regression indicated that compromised performance on ataxia, indicative of cerebellar dysfunction, predicted non-mnemonic and upper motor deficits, whereas low whole blood thiamine level, consistent with limbic circuit dysfunction, predicted mnemonic deficits. This double dissociation indicates biological markers that contribute to heterogeneity in expression of functional impairment in ALC. That non-mnemonic and mnemonic deficits are subserved by the dissociable neural systems of frontocerebellar and limbic circuitry, both commonly disrupted in ALC, suggests neural mechanisms that can differentially affect selective functions, thereby contributing to heterogeneity in pattern and extent of dysfunction in ALC. © 2017 Society for the Study of Addiction.

  12. Hepatic DNA hydroxymethylation is site-specifically altered by chronic alcohol consumption and aging.

    Science.gov (United States)

    Tammen, Stephanie A; Park, Lara K; Dolnikowski, Gregory G; Ausman, Lynne M; Friso, Simonetta; Choi, Sang-Woon

    2017-03-01

    Global DNA hydroxymethylation is markedly decreased in human cancers, including hepatocellular carcinoma, which is associated with chronic alcohol consumption and aging. Because gene-specific changes in hydroxymethylcytosine may affect gene transcription, giving rise to a carcinogenic environment, we determined genome-wide site-specific changes in hepatic hydroxymethylcytosine that are associated with chronic alcohol consumption and aging. Young (4 months) and old (18 months) male C57Bl/6 mice were fed either an ethanol-containing Lieber-DeCarli liquid diet or an isocaloric control diet for 5 weeks. Genomic and gene-specific hydroxymethylcytosine patterns were determined through hydroxymethyl DNA immunoprecipitation array in hepatic DNA. Hydroxymethylcytosine patterns were more perturbed by alcohol consumption in young mice than in old mice (431 differentially hydroxymethylated regions, DhMRs, in young vs 189 DhMRs in old). A CpG island ~2.5 kb upstream of the glucocorticoid receptor gene, Nr3c1, had increased hydroxymethylation as well as increased mRNA expression (p = 0.015) in young mice fed alcohol relative to the control group. Aging alone also altered hydroxymethylcytosine patterns, with 331 DhMRs, but alcohol attenuated this effect. Aging was associated with a decrease in hydroxymethylcytosine ~1 kb upstream of the leptin receptor gene, Lepr, and decreased transcription of this gene (p = 0.029). Nr3c1 and Lepr are both involved in hepatic lipid homeostasis and hepatosteatosis, which may create a carcinogenic environment. These results suggest that the location of hydroxymethylcytosine in the genome is site specific and not random, and that changes in hydroxymethylation may play a role in the liver's response to aging and alcohol.

  13. Chronic Hepatitis C and Alcohol Abuse: The Single Center Experience of Novi Sad - Serbia.

    Science.gov (United States)

    Preveden, Tomislav; Ruzic, Maja; Lendak, Dajana; Pete, Maria; Abenavoli, Ludovico; Brkic, Snezana

    2016-01-01

    Chronic ethyl alcohol consuming is well known independent negative predictor of unfavorable natural course and therapy outcome of Chronic Hepatitis C (CHC) infection. The aim of the present study was to clarify the impact of alcohol consumption on fibrosis rate progression in patients with CHC and Sustained Virologic Response (SVR) rates in patients undergoing treatment with pegylated interferon and ribavirin. This cross sectional retrospective study included 807 CHC patients underwent liver biopsy and hospitalized at Clinical center of Vojvodina, Novi Sad, Serbia. According to the alcohol consumption equal or greater than 50 g/day prior to liver biopsy, patients were divided into two groups. We compared demographic, clinical, virologic and histopathological markers of CHC, as well as response to antiviral therapy. We find statistically significant difference (p=0.001) in gender, but not in age (p=0.081), estimated duration of the CHC (p=0.470) and hepatitis C genotype (p=0.545) between two groups. Among patients with CHC who consume alcohol ≥50 g/day there were significantly higher incidence of intravenous drug users (p=0.000). Binary logistic regression showed that the only independent predictors of moderate to severe fibrosis (fibrosis ≥2) were age (p=0.000) and alcohol use (p=0.027). There was not statistically significant difference in SVR rate between two groups (p=0.810). We believe that this good result in treatment outcome was the consequence of proper selection of patients based primarily on regulations of Republic of Serbia on the necessity of abstinence from the use of alcohol and psychoactive substances at least one year before starting antiviral therapy.

  14. Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption.

    Science.gov (United States)

    Bell, Richard L; Kimpel, Mark W; McClintick, Jeanette N; Strother, Wendy N; Carr, Lucinda G; Liang, Tiebing; Rodd, Zachary A; Mayfield, R Dayne; Edenberg, Howard J; McBride, William J

    2009-11-01

    The objective of this study was to determine the effects of binge-like alcohol drinking on gene expression changes in the nucleus accumbens (ACB) of alcohol-preferring (P) rats. Adult male P rats were given ethanol under multiple scheduled access (MSA; three 1-h dark cycle sessions/day) conditions for 8 weeks. For comparison purposes, a second ethanol drinking group was given continuous/daily alcohol access (CA; 24h/day). A third group was ethanol-naïve (W group). Average ethanol intakes for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hours after the last drinking episode, rats were euthanized, the brains extracted, and the ACB dissected. RNA was extracted and purified for microarray analysis. The only significant differences were between the CA and W groups (palcohol consumption and preference; 4 of these genes (Tgfa, Hspa5, Mtus1 and Creb3l2) are involved in anti-apoptosis and increased transcription, suggesting that they may be contributing to cellular protection and maintaining high alcohol intakes. Overall, these findings suggest that chronic CA drinking results in genomic changes that can be observed during the early acute phase of ethanol withdrawal. Conversely, chronic MSA drinking, with its associated protracted withdrawal periods, results in genomic changes that may be masked by tight regulation of these genes following repeated experiences of ethanol withdrawal.

  15. Housing retention in single-site housing first for chronically homeless individuals with severe alcohol problems.

    Science.gov (United States)

    Collins, Susan E; Malone, Daniel K; Clifasefi, Seema L

    2013-12-01

    We studied housing retention and its predictors in the single-site Housing First model. Participants (n = 111) were chronically homeless people with severe alcohol problems who lived in a single-site Housing First program and participated in a larger nonrandomized controlled trial (2005-2008) conducted in Seattle, Washington. At baseline, participants responded to self-report questionnaires assessing demographic, illness burden, alcohol and other drug use, and psychiatric variables. Housing status was recorded over 2 years. Participants were interested in housing, although a sizable minority did not believe they would be able to maintain abstinence-based housing. Only 23% of participants returned to homelessness during the 2-year follow-up. Commonly cited risk factors--alcohol and other drug use, illness burden, psychiatric symptoms, and homelessness history--did not predict resumed homelessness. Active drinkers were more likely to stay in this housing project than nondrinkers. We found that single-site Housing First programming fills a gap in housing options for chronically homeless people with severe alcohol problems.

  16. A rat model of chronic moderate alcohol consumption and risk of decompression sickness.

    Science.gov (United States)

    Buzzacott, Peter; Mazur, Aleksandra; Wang, Qiong; Lambrechts, Kate; Theron, Michael; Guerrero, François

    2015-06-01

    This study aimed to establish if chronic, moderate, pre-dive alcohol consumption had any affect upon susceptibility to decompression sickness (DCS) in rats. A treatment group of 15 rats were given water containing 12 mL ·L ⁻¹ of ethanol for four weeks. Controls (n = 15) were given water. Both groups were compressed with air to 1,000 kPa, followed by staged decompression. An additional 30 control rats from a similar previous experiment were added, raising the control-treatment ratio to 3:1. Rats in the treatment group consumed the equivalent of an 80 kg man drinking 2 L of 5 % alcohol by volume beer per day, which is three times the recommended daily limit for men. Overall, comparing the treatment group with the combined control groups neither weight (P = 0.23) nor alcohol consumption (P = 0.69) were associated with DCS. We observed that chronic, moderate alcohol consumption prior to compression was neither prophylactic nor deleterious for DCS in young, male rats.

  17. Experimental and Theoretical Mechanistic Investigation of the Iridium-Catalyzed Dehydrogenative Decarbonylation of Primary Alcohols

    DEFF Research Database (Denmark)

    Olsen, Esben Paul Krogh; Singh, Thishana; Harris, Pernille

    2015-01-01

    The mechanism for the iridium-BINAP catalyzed dehydrogenative decarbonylation of primary alcohols with the liberation of molecular hydrogen and carbon monoxide was studied experimentally and computationally. The reaction takes place by tandem catalysis through two catalytic cycles involving...... dehydrogenation of the alcohol and decarbonylation of the resulting aldehyde. The square planar complex IrCl(CO)(rac-BINAP) was isolated from the reaction between [Ir(cod)Cl](2), rac-BINAP, and benzyl alcohol. The complex was catalytically active and applied in the study of the individual steps in the catalytic...... cycles. One carbon monoxide ligand was shown to remain coordinated to iridium throughout the reaction, and release of carbon monoxide was suggested to occur from a dicarbonyl complex. IrH2Cl(CO)(rac-BINAP) was also synthesized and detected in the dehydrogenation of benzyl alcohol. In the same experiment...

  18. Effects of chronic alcoholism in the sensitivity to luminance contrast in vertical sinusoidal gratings

    Directory of Open Access Journals (Sweden)

    Éllen Dias Nicácio da Cruz

    2016-01-01

    Full Text Available Abstract The aim of this study was to measure visual contrast sensitivity (CS of luminance using vertical sinusoidal gratings with spatial frequencies of 0.6, 2.5, 5.0 and 20.0 cycles per degree of visual angle in chronic alcoholics in abstinence period. The participants were 20 volunteers (26–59 years of age divided into two groups: the study group (SG consisted of 10 volunteers with a clinical history of chronic alcoholism abstinence and the control group (CG consisted of 10 healthy volunteers. Each group had five female and five male participants. All participants had normal or corrected visual acuity and were free of identifiable diseases. The psychophysical method of forced choice between two temporal alternatives (2AFC was used to measure visual CS of luminance of 41.2 cd/m2. The results showed significant differences between groups for all spatial frequencies tested (p< 0.001. These results suggest alterations in the visual perception related to chronic alcohol consumption even after years of abstinence.

  19. Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research.

    Science.gov (United States)

    Bujarski, Spencer; Ray, Lara A

    2016-11-01

    In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice.

    Science.gov (United States)

    Peterson, Veronica L; Jury, Nicholas J; Cabrera-Rubio, Raúl; Draper, Lorraine A; Crispie, Fiona; Cotter, Paul D; Dinan, Timothy G; Holmes, Andrew; Cryan, John F

    2017-04-14

    The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (pdiversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (pgut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism.

    Science.gov (United States)

    Ritz, Ludivine; Segobin, Shailendra; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Beaunieux, Hélène; Pitel, Anne L

    2016-09-01

    Alcoholism is associated with widespread brain structural abnormalities affecting mainly the frontocerebellar and the Papez's circuits. Brain glucose metabolism has received limited attention, and few studies used regions of interest approach and showed reduced global brain metabolism predominantly in the frontal and parietal lobes. Even though these studies have examined the relationship between grey matter shrinkage and hypometabolism, none has performed a direct voxel-by-voxel comparison between the degrees of structural and metabolic abnormalities. Seventeen alcoholic patients and 16 control subjects underwent both structural magnetic resonance imaging and (18)F-2-fluoro-deoxy-glucose-positron emission tomography examinations. Structural abnormalities and hypometabolism were examined in alcoholic patients compared with control subjects using two-sample t-tests. Then, these two patterns of brain damage were directly compared with a paired t-test. Compared to controls, alcoholic patients had grey matter shrinkage and hypometabolism in the fronto-cerebellar circuit and several nodes of Papez's circuit. The direct comparison revealed greater shrinkage than hypometabolism in the cerebellum, cingulate cortex, thalamus and hippocampus and parahippocampal gyrus. Conversely, hypometabolism was more severe than shrinkage in the dorsolateral, premotor and parietal cortices. The distinct profiles of abnormalities found within the Papez's circuit, the fronto-cerebellar circuit and the parietal gyrus in chronic alcoholism suggest the involvement of different pathological mechanisms. © The Author(s) 2015.

  2. Moderate alcohol consumption predicts long-term mortality in elderly subjects with chronic heart failure.

    Science.gov (United States)

    Gargiulo, G; Testa, G; Cacciatore, F; Mazzella, F; Galizia, G; Della-Morte, D; Langellotto, A; Pirozzi, G; Ferro, G; Ferrara, N; Rengo, F; Abete, P

    2013-01-01

    Moderate alcohol consumption is related to a reduction of mortality. However, this phenomenon is not well established in the elderly, especially in the presence of chronic heart failure (CHF). The aim of the study was to verify the effect of moderate alcohol consumption on 12-year mortality in elderly community-dwelling with and without CHF. community-dwelling from 5 regions of Italy. A cohort of 1332 subjects aged 65 and older. Mortality after 12-year follow-up in elderly subjects (≥65 years old) with and without CHF was studied. Moderate alcohol consumption was considered ≤250 ml/day (drinkers). In the absence of CHF (n=947), mortality was 42.2% in drinkers vs. 53.7% in non-drinker elderly subjects (p=0.021). In contrast, in the presence of CHF (n=117), mortality was 86.5% in drinkers vs. 69.7% in non-drinker elderly subjects (p=0.004). Accordingly, Cox regression analysis shows that a moderate alcohol consumption is protective of mortality in the absence (HR=0.79; CI 95% 0.66-0.95; pmoderate alcohol consumption is associated with an increased long-term mortality risk in the elderly in the presence of CHF.

  3. Alcohol

    Science.gov (United States)

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  4. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

    Science.gov (United States)

    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  5. Cigarette smoking exacerbates chronic alcohol-induced brain damage: a preliminary metabolite imaging study.

    Science.gov (United States)

    Durazzo, Timothy C; Gazdzinski, Stefan; Banys, Peter; Meyerhoff, Dieter J

    2004-12-01

    Cigarette smoking is common among alcohol-dependent individuals. Nevertheless, previous research has typically not accounted for the potential independent or compounding effects of cigarette smoking on alcohol-induced brain injury and neurocognition. Twenty-four 1-week-abstinent recovering alcoholics (RAs; 14 smokers and 10 nonsmokers) in treatment and 26 light-drinking controls (7 smokers and 19 nonsmokers) were compared on measures of common brain metabolites in gray matter and white matter of the major lobes, basal ganglia, midbrain, and cerebellar vermis, obtained via multislice short-echo time proton magnetic resonance spectroscopic imaging. Smoking and nonsmoking RAs were also contrasted on measures of neurocognitive functioning, as well as laboratory markers of drinking severity and nutritional status. Chronic alcohol dependence, independent of smoking, was associated with lower concentrations of frontal N-acetylaspartate (NAA) and frontal choline-containing compounds, as well as lower parietal and thalamic choline. Smoking RAs had lower NAA concentrations in frontal white matter and midbrain and lower midbrain choline than nonsmoking RAs. A four-group analysis of covariance also demonstrated that chronic cigarette smoking was associated with lower midbrain NAA and choline and with lower vermian choline. In smoking RAs, heavier drinking was associated with heavier smoking, which correlated with numerous subcortical metabolite abnormalities. The 1-week-abstinent smoking and nonsmoking RAs did not differ significantly on a brief neurocognitive battery. In smoking RAs, lower cerebellar vermis NAA was associated with poorer visuomotor scanning speed and incidental learning, and in nonsmoking RAs lower vermis NAA was related to poorer visuospatial learning and memory. These human in vivo proton magnetic resonance spectroscopic imaging findings indicate that chronic cigarette smoking exacerbates chronic alcohol-induced neuronal injury and cell membrane damage in

  6. Exposure to alcohol commercials in movie theatres affects actual alcohol consumption in young adult high weekly drinkers: an experimental study

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Engels, R.C.M.E.

    2011-01-01

    The present pilot study examined the effects of alcohol commercials shown in movie theaters on the alcohol consumption of young adults who see these commercials. A two (alcohol commercials vs. nonalcohol commercials) by two (high weekly alcohol consumption vs. low weekly alcohol consumption)

  7. Exposure to Alcohol Commercials in Movie Theaters Affects Actual Alcohol Consumption in Young Adult High Weekly Drinkers: An Experimental Study

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Engels, R.C.M.E.

    2011-01-01

    The present pilot study examined the effects of alcohol commercials shown in movie theaters on the alcohol consumption of young adults who see these commercials. A two (alcohol commercials vs. nonalcohol commercials) by two (high weekly alcohol consumption vs. low weekly alcohol consumption)

  8. Exposure to alcohol commercials in movie theaters affects actual alcohol consumption in young adult high weekly drinkers: An experimental study

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Engels, R.C.M.E.

    2011-01-01

    The present pilot study examined the effects of alcohol commercials shown in movie theaters on the alcohol consumption of young adults who see these commercials. A two (alcohol commercials vs. nonalcohol commercials) by two (high weekly alcohol consumption vs. low weekly alcohol consumption)

  9. A common variant of PNPLA3 (p.I148M is not associated with alcoholic chronic pancreatitis.

    Directory of Open Access Journals (Sweden)

    Jonas Rosendahl

    Full Text Available BACKGROUND: Chronic pancreatitis (CP is an inflammatory disease that in some patients leads to exocrine and endocrine dysfunction. In industrialized countries the most common aetiology is chronic alcohol abuse. Descriptions of associated genetic alterations in alcoholic CP are rare. However, a common PNPLA3 variant (p.I148M is associated with the development of alcoholic liver cirrhosis (ALC. Since, alcoholic CP and ALC share the same aetiology PNPLA3 variant (p.I148M possibly influences the development of alcoholic CP. METHODS: Using melting curve analysis we genotyped the variant in 1510 patients with pancreatitis or liver disease (961 German and Dutch alcoholic CP patients, 414 German patients with idiopathic or hereditary CP, and 135 patients with ALC. In addition, we included in total 2781 healthy controls in the study. RESULTS: The previously published overrepresentation of GG-genotype was replicated in our cohort of ALC (p-value <0.0001, OR 2.3, 95% CI 1.6-3.3. Distributions of genotype and allele frequencies of the p.I148M variant were comparable in patients with alcoholic CP, idiopathic and hereditary CP and in healthy controls. CONCLUSIONS: The absence of an association of PNPLA3 p.I148M with alcoholic CP seems not to point to a common pathway in the development of alcoholic CP and alcoholic liver cirrhosis.

  10. Toll-like receptor 4 participates in the myelin disruptions associated with chronic alcohol abuse.

    Science.gov (United States)

    Alfonso-Loeches, Silvia; Pascual, Maria; Gómez-Pinedo, Ulises; Pascual-Lucas, Maya; Renau-Piqueras, Jaime; Guerri, Consuelo

    2012-05-01

    Alcohol abuse and alcoholism can cause brain damage, loss of white matter, myelin fiber disruption, and even neuronal injury. The underlying mechanisms of these alterations remain elusive. We have shown that chronic ethanol intake, by activating glial toll-like receptor 4 (TLR4) receptors, triggers the production of inflammatory mediators and can cause brain damage. Because neuroinflammation may be associated with demyelination and neuronal damage, we evaluate whether the ethanol-induced TLR4-dependent proinflammatory environment in the brain could be involved in the myelin disruptions observed in alcoholics. Using brains from wild-type (WT) and TLR4 knockout (KO, TLR4(-/-) ) mice, we demonstrate that chronic ethanol treatment downregulated proteins involved in myelination [proteolipid protein (PLP), myelin basic protein (MBP), myelin-oligodendrocyte glycoprotein, 2,3-cyclic-nucleotide-3-phosphodiesterase, and myelin-associated glycoprotein], while increased chondroitin sulfate proteoglycan NG2 (NG2)-proteoglycan in several brain regions of ethanol-treated WT mice. The immunohistochemistry analysis also revealed that ethanol-treatment-altered myelin morphology reduced the number of MBP-positive fibers and caused oligodendrocyte death, as demonstrated by an increase in caspase-3-positive oligodendrocytes. The in vivo imaging system further confirmed that chronic ethanol intake markedly reduced the PLP in WT mice. Most myelin alterations were not observed in brains from ethanol-treated TLR4(-/-) mice. Electron microscopy studies revealed that although 41-47% of axons showed myelin sheath disarrangements in the cerebral cortex and corpus callosum of WT ethanol-treated mice, respectively, small focal fiber disruptions were noticed in these brain areas of ethanol-treated TLR4(-/-) mice. In summary, the present results suggest that ethanol-induced neuroinflammation might be involved in myelin disruptions and white matter loss observed in human alcoholics. Copyright

  11. The need for fentanyl supplementation of N2O-O2 relaxant anaesthesia in chronic alcoholics.

    Science.gov (United States)

    Tammisto, T; Tigerstedt, I

    1977-01-01

    In order to find out how the need for analgesic supplementation during N2O-O2-relaxant anaesthesia is affected by chronic alcohol consumption, 82 patients with various known alcohol habits were anaesthetized for gastric or biliary surgery. Muscular relaxation was kept constant with the aid of a peripheral neurostimulator, and fentanyl was given in increments of 0.05-0.1 mg for nociceptive symptoms during the anaesthesia. For induction, alcoholics (annual consumption above 151 pure alcohol) needed significantly more thiopental/kg body weight than social drinkers (1--151 annually) or non-alcoholics (less than 11 annually), and excitative symptoms were more frequent in alcoholics. A positive correlation was found between fentanyl supplementation and alcohol consumption (r = 0.41), non-alcoholics requiring on average 3.8 microng/kg/h of fentanyl, as compared with 6.4 microng/kg/h in alcoholics. This correlation was clearer than that found previously under similar conditions by the authors between halothane supplementation and alcohol consumption (r = 0.20). In both studies the correlation was partly due to the higher incidence of gastric surgery among alcoholics, since gastric surgery itself requires more supplementation. An analysis of the different symptoms pointing to the need for fentanyl supplementation revealed that the simultaneous occurrence of several symptoms and the prevalence of motor responses were more common in alcoholics. In one patient halothane had to be used as well. In other patients no special difficulties were observed, and none of the patients reported dreams or recollections. The results suggest that during N2O-O2-relaxant anaesthesia the demand for fentanyl supplementation is increased by about 70% in chronic alcoholics with a mean annual consumption of 311 pure alcohol.

  12. Ultrastructural alterations of choroid plexuses of lateral ventricles of rats (Rattus norvegicus submitted to experimental chronic alcoholism Alterações ultraestruturais dos plexos coróides dos ventrículos laterais de ratos (Rattus norvegicus submetidos a alcoolismo crônico experimental

    Directory of Open Access Journals (Sweden)

    LUÍS FERNANDO TIRAPELLI

    2000-03-01

    Full Text Available Adult male rats (Wistar lineage were alcoholized with sugar cane liquor diluted at 30(0 GL during 300 days and sacrificed every 60 days in 5 stages. Samples of choroid plexuses of lateral ventricles were collected and examined at transmission electronic microscope to detect possible ultrastructural alterations and to raise possible pathological correlations. Gradual changes were observed in these animals during all the experiment: dilatation and enlargement of cisternae of Golgi complex, dilatation of RER, presence of digestive vacuoles and a large amount of pinocytic vesicles as well as vesicles with electronlucent content throughout cytoplasm, as well as an enlargement of intercellular space between basolateral interdigitation of the cells and of the connective tissue. The changes observed in the epithelium and connective tissue of choroid plexuses specially in 240 and 300 days of treatment are presumably due to a disturbance in hydroelectrolitic homeostasis, contributing to several morpho-functional disturbs of central nervous system. No changes were observed in the control group animals.Ratos machos adultos (linhagem Wistar foram alcoolizados com aguardente de cana diluída a 30(0 GL durante 300 dias e sacrificados a cada 60 dias em 5 etapas. Amostras dos plexos coróides dos ventrículos laterais foram coletadas e examinadas ao microscópio eletrônico de transmissão para detectar possíveis alterações ultraestruturais e suas correlações patológicas. Alterações graduais foram observadas nestes animais durante todo o experimento: dilatação e aumento das cisternas de complexo de Golgi, dilatação do retículo endoplasmático rugoso, presença de vacúolos digestivos e grande quantidade de vesículas pinocíticas assim como de vesículas de conteúdo elétron-lúcido por todo o citoplasma, além de aumento do espaço intercelular, entre as interdigitações das células assim como no tecido conjuntivo. As alterações observadas no

  13. Experimental rat models of chronic allograft nephropathy: a review

    Directory of Open Access Journals (Sweden)

    Shrestha B

    2014-07-01

    Full Text Available Badri Shrestha, John HaylorSheffield Kidney Institute, Sheffield Teaching Hospitals NHS Trust, Sheffield, UKAbstract: Chronic allograft nephropathy (CAN is the leading cause of late allograft loss after renal transplantation (RT, which continues to remain an unresolved problem. A rat model of CAN was first described in 1969 by White et al. Although the rat model of RT can be technically challenging, it is attractive because the pathogenesis of CAN is similar to that following human RT and the pathological features of CAN develop within months as compared with years in human RT. The rat model of RT is considered as a useful investigational tool in the field of experimental transplantation research. We have reviewed the literature on studies of rat RT reporting the donor and recipient strain combinations that have investigated resultant survival and histological outcomes. Several different combinations of inbred and outbred rat combinations have been reported to investigate the multiple aspects of transplantation, including acute rejection, cellular and humoral rejection mechanisms and their treatments, CAN, and potential targets for its prevention.Keywords: interventions, therapy, late allograft loss, renal transplantation

  14. Hepatoprotective effect of aged black garlic on chronic alcohol-induced liver injury in rats.

    Science.gov (United States)

    Kim, Min Hee; Kim, Min Ji; Lee, Jeung Hee; Han, Jang Il; Kim, Jin Hee; Sok, Dai-Eun; Kim, Mee Ree

    2011-01-01

    The hepatoprotective effect of aged black garlic (ABG) against ethanol-induced oxidative liver damage was investigated in adult male Sprague-Dawley rats for 4 weeks. Rats were divided into three groups: a saline (WT) group, an ethanol (ET) group (15 mL/kg of body weight 20% [wt/vol] ethanol), and an ethanol + ABG (ET+ABG) group (ethanol + 100 mg/kg of body weight ABG). ABG administration led to decreased epididymal and total fat pad (P<.05) and liver weights, ameliorated prominent fatty changes around the portal triad, and reduced fat accumulation in liver. ABG caused a significant decrease of the alcohol-induced increases in hepatic activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. Cytochrome P450 2E1 activity was reduced by 55%, whereas the activities of glutathione S-transferase and quinine reductase were increased by 1.5-fold (P<.05) and fourfold (P<.05), respectively, in the ET+ABG group compared with the ET group. ABG treatment significantly decreased the thiobarbituric acid-reactive substances level in liver, heart, and plasma. Glutathione content and the activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase in liver were significantly enhanced. Furthermore, the oxidative damage to blood lymphocyte DNA caused by chronic alcohol ingestion was significantly decreased in the ET+ABG group. In conclusion, ABG has strong antioxidative properties and may be a promising agent for protecting against chronic alcohol-induced liver damage.

  15. Effect of abstinence on left ventricular performance in asymptomatic chronic alcoholics

    Energy Technology Data Exchange (ETDEWEB)

    Slutsky, R.; Berger, F.; Garver, P.

    1983-08-01

    Twelve asymptomatic men who were chronic alcoholics (42.3+-10.7 years, mean age +- 1 SD) underwent supine bicycle exercise and gated cardiac blood pool imaging 4-7 days after alcohol withdrawal and then again 32-65 days after abstinence (42.2+-15.0 days). Workloads and exercise stages were identical during both exercise studies. Rest and exercise heart rates, blood pressures, cardiac outputs, double products, and systemic vascular resistances were similar in both studies. Ejection fraction (EF) was higher after abstinence at peak exercise (0,68+-0,07 vs. 0.61+-0.08 P<0.05); end-systolic volume (ESV) was smaller at rest and at peak exercise after abstinence (P<0.05). During the first exercise study, 6 of 12 (50%) subjects did not increase their EF by 0.05 units and 4 of 12 (33%) had no EF increase after abstinence. Even the original ''normal'' responders had greater rest and exercise EFs after abstinence. In the first exercise study end diastolic volume (EDV) rose during exercise (P<0.05) while ESV did not change. After abstinence, EDV did not change during exercise, while ESV declined (P<0.05). These results show that latent cardiac dysfunction exists in asymptomatic chronic alcoholics, which is partially although not completely resolved by abstinence of brief periods.

  16. Neurocognitive impairment due to chronic alcohol consumption in an American Indian community.

    Science.gov (United States)

    Harris, C R; Albaugh, B; Goldman, D; Enoch, M A

    2003-07-01

    Studies have shown that clinically ascertained alcoholics tend to have lower scores than nonalcoholics on cognitive performance tests, particularly the Block Design (BD) and Digit Symbol (DS) tests of the Weschler Adult Intelligence Scale-Revised (WAIS-R). The aim of this study was to determine whether similar differences are found in a community sample of Plains Indian men and women with an episodic pattern of drinking and a high lifetime prevalence of alcoholism (71% for men, 44% for women). We administered a truncated form of the WAIS-R to 334 members of a Plains Indian tribe (197 women and 137 men). Blind-rated psychiatric diagnoses were assigned according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III-R) criteria and based on the Schedule for Affective Disorders, Lifetime Version (SADS-L) interview. We compared 68 currently drinking alcoholics (38 men and 30 women), 116 abstaining alcoholics (59 men and 57 women) and 150 nonalcoholics (40 men and 110 women). Current and past heavy drinking had no impact on WAIS-R scores in women. Male alcoholics who were abstinent > or = 2years had similar scores to nonalcoholic men. Male current drinkers showed a trend for lower overall verbal and performance (PIQ) scores and BD performance subtest. Further analysis showed that drinking for > or = 15 years was significantly associated with reduced DS in male current drinkers. These findings suggest that for the men in this community sample, the impact on PIQ is due to the direct effect of chronic alcohol consumption on cognitive performance and is at least partially reversible after 2 years of abstinence.

  17. Alcohol prevention at sporting events: study protocol for a quasi-experimental control group study

    Directory of Open Access Journals (Sweden)

    Natalie Durbeej

    2016-06-01

    Full Text Available Abstract Background Alcohol intoxication and overserving of alcohol at sporting events are of great concern, given the relationships between alcohol consumption, public disturbances, and violence. During recent years this matter has been on the agenda for Swedish policymakers, authorities and key stakeholders, with demands that actions be taken. There is promising potential for utilizing an environmental approach to alcohol prevention as a strategy to reduce the level of alcohol intoxication among spectators at sporting events. Examples of prevention strategies may be community mobilization, Responsible Beverage Service training, policy work, and improved controls and sanctions. This paper describes the design of a quasi-experimental control group study to examine the effects of a multi-component community-based alcohol intervention at matches in the Swedish Premier Football League. Methods A baseline assessment was conducted during 2015 and at least two follow-up assessments will be conducted in 2016 and 2017. The two largest cities in Sweden are included in the study, with Stockholm as the intervention area and Gothenburg as the control area. The setting is Licensed Premises (LP inside and outside Swedish football arenas, in addition to arena entrances. Spectators are randomly selected and invited to participate in the study by providing a breath alcohol sample as a proxy for Blood Alcohol Concentration (BAC. Actors are hired and trained by an expert panel to act out a standardized scene of severe pseudo-intoxication. Four types of cross-sectional data are generated: (i BAC levels among ≥ 4 200 spectators, frequency of alcohol service to pseudo-intoxicated patrons attempting to purchase alcohol at LP (ii outside the arenas (≥200 attempts and (iii inside the arenas (≥ 200 attempts, and (iv frequency of security staff interventions towards pseudo-intoxicated patrons attempting to enter the arenas (≥ 200 attempts. Discussion There

  18. Alcohol prevention at sporting events: study protocol for a quasi-experimental control group study.

    Science.gov (United States)

    Durbeej, Natalie; Elgán, Tobias H; Jalling, Camilla; Gripenberg, Johanna

    2016-06-06

    Alcohol intoxication and overserving of alcohol at sporting events are of great concern, given the relationships between alcohol consumption, public disturbances, and violence. During recent years this matter has been on the agenda for Swedish policymakers, authorities and key stakeholders, with demands that actions be taken. There is promising potential for utilizing an environmental approach to alcohol prevention as a strategy to reduce the level of alcohol intoxication among spectators at sporting events. Examples of prevention strategies may be community mobilization, Responsible Beverage Service training, policy work, and improved controls and sanctions. This paper describes the design of a quasi-experimental control group study to examine the effects of a multi-component community-based alcohol intervention at matches in the Swedish Premier Football League. A baseline assessment was conducted during 2015 and at least two follow-up assessments will be conducted in 2016 and 2017. The two largest cities in Sweden are included in the study, with Stockholm as the intervention area and Gothenburg as the control area. The setting is Licensed Premises (LP) inside and outside Swedish football arenas, in addition to arena entrances. Spectators are randomly selected and invited to participate in the study by providing a breath alcohol sample as a proxy for Blood Alcohol Concentration (BAC). Actors are hired and trained by an expert panel to act out a standardized scene of severe pseudo-intoxication. Four types of cross-sectional data are generated: (i) BAC levels among ≥ 4 200 spectators, frequency of alcohol service to pseudo-intoxicated patrons attempting to purchase alcohol at LP (ii) outside the arenas (≥200 attempts) and (iii) inside the arenas (≥ 200 attempts), and (iv) frequency of security staff interventions towards pseudo-intoxicated patrons attempting to enter the arenas (≥ 200 attempts). There is an urgent need nationally and internationally to

  19. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Sarah M. DeNucci

    2010-01-01

    Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

  20. Moderate Alcohol Consumption and Chronic Disease: The Case for a Long-Term Trial

    Science.gov (United States)

    Mukamal, Kenneth J.; Clowry, Catherine M.; Murray, Margaret M.; Hendriks, Henk F.J.; Rimm, Eric B.; Sink, Kaycee M.; Adebamowo, Clement A.; Dragsted, Lars O.; Lapinski, P. Scott; Lazo, Mariana; Krystal, John H.

    2016-01-01

    Drinking within recommended limits is highly prevalent in much of the world, and strong epidemiological associations exist between moderate alcohol consumption and risk of several major chronic diseases, including coronary heart disease, diabetes, and breast cancer. In many cases, plausible biological mediators for these associations have been identified in randomized trials, but gold-standard evidence that moderate drinking causes or prevents any chronic disease remains elusive and important concerns about available evidence have been raised. Although long-term randomized trials to test the observed associations have been termed impossible, clinical investigators have now successfully completed randomized trials of complex nutritional interventions in a variety of settings, along with trials of alcohol consumption itself of up to two years duration. The successful completion of these trials suggests that objections to the execution of a full-scale long-term clinical trial of moderate drinking on chronic disease are increasingly untenable. We present potential lessons learned for such a trial and discuss key features to maximize its feasibility and value. PMID:27688006

  1. Modulation of the effects of alcohol on driving-related psychomotor skills by chronic exposure to cannabis.

    Science.gov (United States)

    Wright, A; Terry, P

    2002-03-01

    Many previous studies have reported that alcohol and cannabis produce additive psychomotor effects in acute combination, but few have explicitly tested whether chronic exposure to cannabis, in the absence of acute administration, alters the effects of alcohol on psychomotor performance. To test whether long-term cannabis use modulates the effects of alcohol on psychomotor skills and self-reported mood and sensation. Regular cannabis users (minimum: daily use for at least 3 years) and infrequent users (maximum: once-monthly use for at most 3 years) were matched for sex, age, alcohol intake and other drug use (14 participants in each group). Participants received alcohol (females 0.35 g/kg; males 0.45 g/kg) and placebo drinks. By urinalysis, only regular users tested positive for metabolites of Delta(9)-tetrahydrocannabinol; breath alcohol levels were similar between groups. Participants were tested on a computerised tracking task that has been used to screen drugs for adverse effects on driving. The task involved tracking a moving target on a computer screen while simultaneously responding to occasional presentations of stimuli in the periphery of the screen. Tracking accuracy was similar for both groups after placebo, but alcohol caused a significant deterioration in performance among infrequent cannabis users relative to regular users. These changes were mirrored by significant changes in self-reported scores for dizziness, measured by visual analogue scales. Alcohol slowed reaction times, but not differentially between groups. For psychomotor skills relevant to driving, chronic cannabis use (in the absence of acute administration) does not potentiate the effects of alcohol. In fact, the superior tracking accuracy of regular users relative to infrequent users after alcohol, and their lower scores for dizziness, suggest that chronic cannabis use may instead confer cross-tolerance to specific effects of alcohol on behaviour.

  2. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P Rats.

    Directory of Open Access Journals (Sweden)

    Jessica Godfrey

    Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels

  3. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats.

    Science.gov (United States)

    Godfrey, Jessica; Jeanguenin, Lisa; Castro, Norma; Olney, Jeffrey J; Dudley, Jason; Pipkin, Joseph; Walls, Stanley M; Wang, Wei; Herr, Deron R; Harris, Greg L; Brasser, Susan M

    2015-01-01

    Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P) rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total) or were given access only to water (control). Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4)-desaturase (Degs2), an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels achieved by

  4. Chronic disease and recent addiction treatment utilization among alcohol and drug dependent adults

    Directory of Open Access Journals (Sweden)

    Samet Jeffrey

    2011-10-01

    Full Text Available Abstract Background Chronic medical diseases require regular and longitudinal care and self-management for effective treatment. When chronic diseases include substance use disorders, care and treatment of both the medical and addiction disorders may affect access to care and the ability to focus on both conditions. The objective of this paper is to evaluate the association between the presence of chronic medical disease and recent addiction treatment utilization among adults with substance dependence. Methods Cross-sectional secondary data analysis of self-reported baseline data from alcohol and/or drug-dependent adults enrolled in a randomized clinical trial of a disease management program for substance dependence in primary care. The main independent variable was chronic medical disease status, categorized using the Katz Comorbidity Score as none, single condition of lower severity, or higher severity (multiple conditions or single higher severity condition, based on comorbidity scores determined from self-report. Asthma was also examined in secondary analyses. The primary outcome was any self-reported addiction treatment utilization (excluding detoxification in the 3 months prior to study entry, including receipt of any addiction-focused counseling or addiction medication from any healthcare provider. Logistic regression models were adjusted for sociodemographics, type of substance dependence, recruitment site, current smoking, and recent anxiety severity. Results Of 563 subjects, 184 (33% reported any chronic disease (20% low severity; 13% higher severity and 111 (20% reported asthma; 157 (28% reported any addiction treatment utilization in the past 3 months. In multivariate regression analyses, no significant effect was detected for chronic disease on addiction treatment utilization (adjusted odds ratio [AOR] 0.88 lower severity vs. none, 95% confidence interval (CI: 0.60, 1.28; AOR 1.29 higher severity vs. none, 95% CI: 0.89, 1.88 nor for

  5. Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala.

    Science.gov (United States)

    Varodayan, Florence P; Bajo, Michal; Soni, Neeraj; Luu, George; Madamba, Samuel G; Schweitzer, Paul; Roberto, Marisa

    2017-05-01

    The basolateral nucleus of the amygdala (BLA) is critical to the pathophysiology of anxiety-driven alcohol drinking and relapse. The endogenous cannabinoid/type 1 cannabinoid receptor (eCB/CB1 ) system curbs BLA-driven anxiety and stress responses via a retrograde negative feedback system that inhibits neurotransmitter release, and BLA CB1 activation reduces GABA release and drives anxiogenesis. Additionally, decreased amygdala CB1 is observed in abstinent alcoholic patients and ethanol withdrawn rats. Here, we investigated the potential disruption of eCB/CB1 signaling on GABAergic transmission in BLA pyramidal neurons of rats exposed to 2-3 weeks intermittent ethanol. In the naïve rat BLA, the CB1 agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent activity. This retrograde tonic eCB/CB1 signaling was diminished in chronic ethanol exposed rats, suggesting a functional impairment of the eCB/CB1 system. In contrast, acute ethanol increased GABAergic transmission similarly in naïve and chronic ethanol exposed rats, via both presynaptic and postsynaptic mechanisms. Notably, CB1 activation impaired ethanol's facilitation of GABAergic transmission across both groups, but the AM251-induced and ethanol-induced facilitation of GABA release was additive, suggesting independent presynaptic sites of action. Collectively, the present findings highlight a critical CB1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state. © 2016 Society for the Study of Addiction.

  6. Quantitative analysis of nanoscale intranuclear structural alterations in hippocampal cells in chronic alcoholism via transmission electron microscopy imaging

    Science.gov (United States)

    Sahay, Peeyush; Shukla, Pradeep K.; Ghimire, Hemendra M.; Almabadi, Huda M.; Tripathi, Vibha; Mohanty, Samarendra K.; Rao, Radhakrishna; Pradhan, Prabhakar

    2017-04-01

    Chronic alcoholism is known to alter the morphology of the hippocampus, an important region of cognitive function in the brain. Therefore, to understand the effect of chronic alcoholism on hippocampal neural cells, we employed a mouse model of chronic alcoholism and quantified intranuclear nanoscale structural alterations in these cells. Transmission electron microscopy (TEM) images of hippocampal neurons were obtained, and the degree of structural alteration in terms of mass density fluctuation was determined using the light-localization properties of optical media generated from TEM imaging. The results, which were obtained at length scales ranging from ~30 to 200 nm, show that 10-12 week-old mice fed a Lieber-DeCarli liquid (alcoholic) diet had a higher degree of structural alteration than control mice fed a normal diet without alcohol. The degree of structural alteration became significantly distinguishable at a sample length of ~100 nm, which is the typical length scale of the building blocks of cells, such as DNA, RNA, proteins and lipids. Interestingly, different degrees of structural alteration at such length scales suggest possible structural rearrangement of chromatin inside the nuclei in chronic alcoholism.

  7. A case of posterior reversible encephalopathy syndrome associated with acute pancreatitis and chronic alcoholism.

    Science.gov (United States)

    Baek, Hyun Seok; Lee, Se-Jin

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a variety of clinical disorders. The authors encountered a case of PRES associated with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema at the bilateral posterior temporal and parieto-occipital lobes and cerebellum. Laboratory tests and abdominal computed tomography (CT) revealed acute pancreatitis. The patient recovered completely, and follow-up brain MRI and abdominal CT exhibited resolution of the previous lesions. We suggest that acute pancreatitis might be an etiology of PRES. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Impaired response inhibition in the rat 5 choice continuous performance task during protracted abstinence from chronic alcohol consumption.

    Directory of Open Access Journals (Sweden)

    Cristina Irimia

    Full Text Available Impaired cognitive processing is a hallmark of addiction. In particular, deficits in inhibitory control can propel continued drug use despite adverse consequences. Clinical evidence shows that detoxified alcoholics exhibit poor inhibitory control in the Continuous Performance Task (CPT and related tests of motor impulsivity. Animal models may provide important insight into the neural mechanisms underlying this consequence of chronic alcohol exposure though pre-clinical investigations of behavioral inhibition during alcohol abstinence are sparse. The present study employed the rat 5 Choice-Continuous Performance Task (5C-CPT, a novel pre-clinical variant of the CPT, to evaluate attentional capacity and impulse control over the course of protracted abstinence from chronic intermittent alcohol consumption. In tests conducted with familiar 5C-CPT conditions EtOH-exposed rats exhibited impaired attentional capacity during the first hours of abstinence and impaired behavioral restraint (increased false alarms during the first 5d of abstinence that dissipated thereafter. Subsequent tests employing visual distractors that increase the cognitive load of the task revealed significant increases in impulsive action (premature responses at 3 and 5 weeks of abstinence, and the emergence of impaired behavioral restraint (increased false alarms at 7 weeks of abstinence. Collectively, these findings demonstrate the emergence of increased impulsive action in alcohol-dependent rats during protracted alcohol abstinence and suggest the 5C-CPT with visual distractors may provide a viable behavioral platform for characterizing the neurobiological substrates underlying impaired behavioral inhibition resulting from chronic intermittent alcohol exposure.

  9. Hepatoprotective Effect of Albumin Peptides from Corn Germ Meal on Chronic Alcohol-Induced Liver Injury in Mice.

    Science.gov (United States)

    Yu, Yali; Wang, Lijun; Wang, Ying; Lin, Dingbo; Liu, Jingbo

    2017-10-30

    Despite the fact that chronic and excessive alcohol consumption is a risk factor for many chronic diseases, such as a fatty liver disease, the addictive power of alcohol is strong worldwide. Corn germ meal albumin peptides (CGMAPs), by-products in corn germ oil industry have often been considered as wastes disposal in food processing. The aim of this study was to investigate the hepatoprotective effect of CGMAPs on chronic alcohol-induced liver injury in a mouse model. The corn germ meal-derived albumin was enzymatically hydrolysed, and the albumin peptides fractions (APFs) with Mw APF4) was collected. APF4 was an oligopeptide with a high Fischer's ratio (F > 3), rich in glutamic, alanine, leucine and proline. The hydrophobic Q value was 5.1, indicating the property of high enrichment in hydrophobic amino acids. Alcohol administration significantly increased the activities and levels of hepatic aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and triglycerides (TG) (P APF4 at 800 mg/kg bw. Thus, APF4 of CGMAPs had a significant protective effect against chronic alcohol-induced liver injury through enhancement of in vivo antioxidant ability as a possible mechanism of action, which therefore suggested that APF4 might be useful as natural sources to protect liver from alcoholic damage. Corn germ meal albumin peptides (CGMAPs) of Mw < 1 kDa, a kind of bioactive peptides which could effectively improve alcohol metabolism and protect against the hepatic damage induced by alcohol, might be useful as natural sources to protect liver from alcoholic damage. © 2017 Institute of Food Technologists®.

  10. A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

    Science.gov (United States)

    Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

    2016-04-01

    Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P liver (2.5-fold, P liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Aloin protects against chronic alcoholic liver injury via attenuating lipid accumulation, oxidative stress and inflammation in mice.

    Science.gov (United States)

    Cui, Yan; Ye, Qing; Wang, Heya; Li, Yingchao; Xia, Xiuhua; Yao, Weirong; Qian, He

    2014-12-01

    The present study was designed to investigate the protective effect of aloin against alcoholic liver disease in a chronic alcohol feeding mouse model. Mice were given alcohol twice a day by intragastric administration for 11 weeks (4.0, 4.7, 5.5 g/kg bw/day for the first 3 weeks respectively, 6.3 g/kg bw/day for the following 8 weeks). Aloin (10, 30 mg/kg bw) or vehicle was given by gavage to mice after each alcohol administration. Alcohol elevated the serum transaminases alanine aminotransferase, aspartate aminotransferase, total cholesterol and triglyceride levels which were significantly attenuated by the co-administration of aloin (p aloin significantly suppressed the alcohol-dependent induction of sterol regulatory element-binding protein-1c expression (p aloin supplementation significantly inhibited the alcohol-dependent elevation of malondialdehyde and cytochrome P4502E1 expression (p aloin (p aloin may represent a novel, protective strategy against chronic alcoholic liver injury by attenuating lipid accumulation, oxidative stress and LPS-induced inflammatory response.

  12. Chronic ethanol consumption increases dopamine uptake in the nucleus accumbens of high alcohol drinking rats.

    Science.gov (United States)

    Carroll, Michelle R; Rodd, Zachary A; Murphy, James M; Simon, Jay R

    2006-10-01

    Past research has indicated that chronic ethanol exposure enhances dopamine (DA) neurotransmission in several brain regions. The present study examined the effects of chronic ethanol drinking on dopamine transporter (DAT) function in the nucleus accumbens (Acb) of High-Alcohol-Drinking replicate line 1 (HAD-1) rats. HAD rats were given concurrent 24-h access to 15% ethanol and water or water alone for 8 weeks. Subsequently, DA uptake and the V(max) of the DAT were compared between the two groups using homogenates of the nucleus accumbens. DA uptake was measured following a 2 min incubation at 37 degrees C in the presence of 8 nM [(3)H]DA. For kinetic analyses, DA uptake was assessed in the presence of 5 concentrations of [(3)H]DA ranging from 8 nM to 500 nM. Analyses of the data revealed a significant increase in DA uptake in the ethanol group compared to water controls. Kinetic analyses revealed the change in DA uptake to be a consequence of an increase in the V(max) of transport. These findings demonstrate that chronic free-choice oral ethanol consumption in HAD-1 female rats increases DA uptake in the Acb by increasing the V(max) of the transporter. However, it is not known whether the ethanol-induced change in V(max) is caused by differences in the actual number of available transporter sites or from a difference in the velocity of operation of a similar number of transporters. Overall, the data indicate that chronic ethanol consumption by HAD-1 rats produces prolonged neuroadaptations within the mesolimbic DA system, which may be important for the understanding of the neurobiological basis of alcoholism.

  13. Effect of chronic administration of alcoholic beverages and seasoning containing alcohol on hepatic ethanol metabolism in mice.

    Science.gov (United States)

    Kishimoto, R; Ueda, M; Kawakami, M; Goda, K; Park, S S; Nakata, Y

    1997-12-01

    Five-week-old male mice, C3H/HeNCrj (C3H/He), were given a 5% (v/v) ethanol solution, commercial alcoholic beverages (Japanese sake (sake) or red wine) or a Japanese seasoning (mirin [containing ethanol and a large amount of glucose]) ad libitum for 45 d, and were then examined for changes in the hepatic enzymes related to ethanol metabolism 2 h after oral administration of 5 g of ethanol/kg body weight. The specific activity of aniline hydroxylase (ANH) in the hepatic microsome increased significantly in all groups chronically administered ethanol solution, sake, red wine or mirin, and the greatest increase was in the hepatic microsome of mirin-administered mice. The cytochrome P-450 (CYP) 2E1 increased in the hepatic microsome of the mice administered ethanol solution, red wine or mirin where accompanied by high ANH activity. The immunoreactive band for CYP1A1 showed high specificity in the microsome of mice given sake, red wine or mirin. It was assumed that CYP1A1 was induced by unknown component(s) other than ethanol in these solutions. In the cytosolic fraction, following the chronic administration of sake and mirin, the total aldehyde dehydrogenase (A1DH) activity with high-Km decreased significantly. In the mitochondrial fraction, the activity of high-Km A1DH increased significantly in the mirin-administered mice which drank a large amount of ethanol, whereas that in the red wine-administered group tended to decrease. These results indicate that the enzyme activities related to the oxidation of both ethanol and acetaldehyde in the cytosolic, mitochondrial and microsomal fractions of the liver were affected by either the action of ethanol or its interaction with other constituents of sake, red wine and mirin.

  14. Protective effect of curcumin against chronic alcohol-induced cognitive deficits and neuroinflammation in the adult rat brain.

    Science.gov (United States)

    Tiwari, V; Chopra, K

    2013-08-06

    Chronic alcohol intake is known to induce the selective neuronal damage associated with increase oxidative-nitrosative stress and activation of inflammatory cascade finally resulting in cognitive deficits. In the present study, we investigated the protective effect of curcumin, a potent natural anti-oxidant and anti-inflammatory molecule against chronic alcohol-induced cognitive dysfunction and nuclear factor kappa beta (NF-κβ) mediated inflammatory signaling in the brain of rats chronically administered ethanol. Male Wistar rats were given ethanol (10 g/kg; oral gavage) for 10 weeks, and treated with curcumin (15, 30 and 60 mg/kg) for the same duration. Ethanol-exposed rats showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)), NF-kβ and caspase-3 levels in different brain regions (cerebral cortex and hippocampus) of ethanol-treated rats. Co-administration with curcumin significantly and dose-dependently prevented all the behavioral, biochemical and molecular alterations in rats chronically administered ethanol. Thus, findings from the current study demonstrates the possible involvement of oxidative-nitrosative stress mediated cytokine release and inflammatory signaling in chronic alcohol-induced cognitive dysfunction and also suggests the effectiveness of curcumin in preventing cognitive deficits associated with chronic alcohol consumption. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking.

    Science.gov (United States)

    Leão, Rodrigo M; Cruz, Fábio C; Vendruscolo, Leandro F; de Guglielmo, Giordano; Logrip, Marian L; Planeta, Cleopatra S; Hope, Bruce T; Koob, George F; George, Olivier

    2015-04-15

    Alcohol and nicotine are the two most co-abused drugs in the world. Previous studies have shown that nicotine can increase alcohol drinking in nondependent rats, yet it is unknown whether nicotine facilitates the transition to alcohol dependence. We tested the hypothesis that chronic nicotine will speed up the escalation of alcohol drinking in rats and that this effect will be accompanied by activation of sparsely distributed neurons (neuronal ensembles) throughout the brain that are specifically recruited by the combination of nicotine and alcohol. Rats were trained to respond for alcohol and made dependent using chronic, intermittent exposure to alcohol vapor, while receiving daily nicotine (0.8 mg/kg) injections. Identification of neuronal ensembles was performed after the last operant session, using immunohistochemistry. Nicotine produced an early escalation of alcohol drinking associated with compulsive alcohol drinking in dependent, but not in nondependent rats (air exposed), as measured by increased progressive-ratio responding and increased responding despite adverse consequences. The combination of nicotine and alcohol produced the recruitment of discrete and phenotype-specific neuronal ensembles (∼4-13% of total neuronal population) in the nucleus accumbens core, dorsomedial prefrontal cortex, central nucleus of the amygdala, bed nucleus of stria terminalis, and posterior ventral tegmental area. Blockade of nicotinic receptors using mecamylamine (1 mg/kg) prevented both the behavioral and neuronal effects of nicotine in dependent rats. These results demonstrate that nicotine and activation of nicotinic receptors are critical factors in the development of alcohol dependence through the dysregulation of a set of interconnected neuronal ensembles throughout the brain. Copyright © 2015 the authors 0270-6474/15/356241-13$15.00/0.

  16. Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning.

    Science.gov (United States)

    Cui, S Q; Wang, Q; Zheng, Y; Xiao, B; Sun, H W; Gu, X L; Zhang, Y C; Fu, C H; Dong, P X; Wang, X M

    2015-06-01

    We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (Peffects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

  17. Genetically Determined Chronic Pancreatitis but not Alcoholic Pancreatitis Is a Strong Risk Factor for Pancreatic Cancer.

    Science.gov (United States)

    Midha, Shallu; Sreenivas, Vishnubhatla; Kabra, Madhulika; Chattopadhyay, Tushar Kanti; Joshi, Yogendra Kumar; Garg, Pramod Kumar

    2016-11-01

    To study if chronic pancreatitis (CP) is a risk factor for pancreatic cancer. Through a cohort and a case-control study design, CP and other important risk factors including smoking, diabetes, alcohol, obesity, and genetic mutations were studied for their association with pancreatic cancer. In the cohort study, 402 patients with CP were included. During 3967.74 person-years of exposure, 5 of the 402 patients (4 idiopathic CP, 1 hereditary CP) developed pancreatic cancer after 16.60 ± 3.51 years of CP. The standardized incidence ratio was 121. In the case-control study, 249 pancreatic cancer patients and 1000 healthy controls were included. Of the 249 patients with pancreatic cancer, 24 had underlying idiopathic CP, and none had alcoholic pancreatitis. SPINK1 gene mutation was present in 16 of 26 patients with idiopathic CP who had pancreatic cancer. Multivariable analysis showed CP (odds ratio [OR], 97.67; 95% confidence interval [CI], 12.69-751.36), diabetes (>4 years duration) (OR, 3.05; 95% CI, 1.79-5.18), smoking (OR, 1.93; 95% CI, 1.38-2.69) as significant risk factors for pancreatic cancer. The population attributable risk was 9.41, 9.06, and 9.50 for diabetes, CP, and smoking, respectively. Genetically determined CP but not alcoholic CP is a strong risk factor for pancreatic cancer.

  18. THE ANTIOXIDANT AND ANTIAPOPTOTIC EFFECT OF BORIC ACID ON HEPATOXICITY IN CHRONIC ALCOHOL-FED RATS.

    Science.gov (United States)

    Sogut, Ibrahim; Paltun, Sıla Ozlem; Tuncdemir, Matem; Ersoz, Melike; Hurdag, Canan

    2017-09-12

    The harmful use alcohol is a worldwide problem involving all ages. This study aims to investigate chronic alcohol exposure related hepatotoxicity on the rats liver and possible hepatoprotective effects of boric acid. Rats were separated into four different group: control, ethanol, ethanol+boric acid and boric acid. We measured malondialdehyde levels (MDA), total sialic acid (TSA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels which are known to be the markers of alcohol damage and also caspase-3, tumor necrosis factor-alpha (TNF-α) and the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) as the markers of apoptosis were measured. In ethanol group MDA, TSA and TNF-α levels increased whereas SOD and CAT levels decreased compared with control group. Ethanol+boric acid group MDA, TSA, caspase-3 and TNF-α levels decreased whereas SOD and CAT levels increased compared with ethanol group. Histopathological evaluation of light microscope images, immunohistochemical caspase-3 and TNF-α activity in the ethanol+boric acid group were shown to be decreased compared with that in the ethanol group. Our result revealed that ethanol is capable of triggering oxidative stress and apoptosis in the rat liver. We propose that boric acid is an effective compound in protecting the rat liver against ethanol.

  19. Chronic care management for dependence on alcohol and other drugs: the AHEAD randomized trial.

    Science.gov (United States)

    Saitz, Richard; Cheng, Debbie M; Winter, Michael; Kim, Theresa W; Meli, Seville M; Allensworth-Davies, Don; Lloyd-Travaglini, Christine A; Samet, Jeffrey H

    2013-09-18

    People with substance dependence have health consequences, high health care utilization, and frequent comorbidity but often receive poor-quality care. Chronic care management (CCM) has been proposed as an approach to improve care and outcomes. To determine whether CCM for alcohol and other drug dependence improves substance use outcomes compared with usual primary care. The AHEAD study, a randomized trial conducted among 563 people with alcohol and other drug dependence at a Boston, Massachusetts, hospital-based primary care practice. Participants were recruited from September 2006 to September 2008 from a freestanding residential detoxification unit and referrals from an urban teaching hospital and advertisements; 95% completed 12-month follow-up. Participants were randomized to receive CCM (n=282) or no CCM (n=281). Chronic care management included longitudinal care coordinated with a primary care clinician; motivational enhancement therapy; relapse prevention counseling; and on-site medical, addiction, and psychiatric treatment, social work assistance, and referrals (including mutual help). The no CCM (control) group received a primary care appointment and a list of treatment resources including a telephone number to arrange counseling. The primary outcome was self-reported abstinence from opioids, stimulants, or heavy drinking. Biomarkers were secondary outcomes. There was no significant difference in abstinence from opioids, stimulants, or heavy drinking between the CCM (44%) and control (42%) groups (adjusted odds ratio, 0.84; 95% CI, 0.65-1.10; P=.21). No significant differences were found for secondary outcomes of addiction severity, health-related quality of life, or drug problems. No subgroup effects were found except among those with alcohol dependence, in whom CCM was associated with fewer alcohol problems (mean score, 10 vs 13; incidence rate ratio, 0.85; 95% CI, 0.72-1.00; P=.048). Among persons with alcohol and other drug dependence, CCM compared

  20. Altered Distribution of Peripheral Blood Maturation-Associated B-Cell Subsets in Chronic Alcoholism.

    Science.gov (United States)

    Almeida, Julia; Polvorosa, Maria Angeles; Gonzalez-Quintela, Arturo; Madruga, Ignacio; Marcos, Miguel; Pérez-Nieto, Maria Angeles; Hernandez-Cerceño, Maria Luisa; Orfao, Alberto; Laso, Francisco Javier

    2015-08-01

    Although decreased counts of peripheral blood (PB) B cells-associated with an apparently contradictory polyclonal hypergammaglobulinemia-have been reported in chronic alcoholism, no information exists about the specific subsets of circulating B cells altered and their relationship with antibody production. Here, we analyzed for the first time the distribution of multiple maturation-associated subpopulations of PB B cells in alcoholism and its potential relationship with the onset of liver disease. PB samples from 35 male patients-20 had alcoholic hepatitis (AH) and 15 chronic alcoholism without liver disease (AWLD)-were studied, in parallel to 19 male healthy donors (controls). The distribution of PB B-cell subsets (immature/regulatory, naïve, CD27(-) and CD27(+) memory B lymphocytes, and circulating plasmablasts of distinct immunoglobulin-Ig-isotypes) was analyzed by flow cytometry. Patients with AH showed significantly decreased numbers of total PB B lymphocytes (vs. controls and AWLD), at the expense of immature, memory, and, to a lesser extent, also naïve B cells. AWLD showed reduced numbers of immature and naïve B cells (vs. controls), but higher PB counts of plasmablasts (vs. the other 2 groups). Although PB memory B cells were reduced among the patients, the percentage of surface (s)IgA(+) cells (particularly CD27(-) /sIgA(+) cells) was increased in AH, whereas both sIgG(+) and sIgA(+) memory B cells were significantly overrepresented in AWLD versus healthy donors. Regarding circulating plasmablasts, patients with AH only showed significantly reduced counts of sIgG(+) cells versus controls. In contrast, the proportion of both sIgA(+) and sIgG(+) plasmablasts-from all plasmablasts-was reduced in AH and increased in AWLD (vs. the other 2 groups). AH and AWLD patients display a significantly reduced PB B-cell count, at the expense of decreased numbers of recently produced immature/regulatory B cells and naïve B cells, together with an increase in Ig

  1. Impairment due to alcohol, tetrahydrocannabinol, and benzodiazepines in impaired drivers compared to experimental studies.

    Science.gov (United States)

    Høiseth, Gudrun; Berg-Hansen, Grim Otto; Øiestad, Åse Marit L; Bachs, Liliana; Mørland, Jørg

    2017-04-03

    In some countries, per se laws for other drugs than alcohol are used to judge drunk and drugged drivers. These blood concentration limits are often derived from experimental studies on traffic relevant behavior of healthy volunteers. Knowledge about how results from experimental studies could be transferred to a real-life setting is missing. The aim of this study was to compare impairment seen in experimental studies to the impairment seen at equivalent concentrations in apprehended drunk and drugged drivers. Results from previously performed meta-analyses of experimental studies regarding impairment from alcohol, tetrahydrocannabinol (THC), and benzodiazepines were compared to impairment in apprehended drunk and drugged drivers as judged by a clinical test of impairment. Both experimental studies and real-life cases were divided into 4 groups according to increasing blood drug concentration intervals. The percentage of impaired test results in experimental studies was compared to the percentage of impaired subjects among drivers within the same blood drug concentration window. For ethanol, the percentage of impaired drivers (n = 1,223) increased from 59% in the lowest drug concentration group to 95% in the highest drug concentration group, compared to 7 and 72% in the respective groups in experimental studies. For THC, the percentage of impaired drivers (n = 950) increased from 42 to 58%, the corresponding numbers being 11 and 42% for experimental studies. For benzodiazepines, the percentage of impaired drivers (n = 245) increased from 46 to 76%, the corresponding numbers being 16 and 60% for experimental studies. The increased odds ratio for impairment between 2 concentration groups was comparable for experimental studies and impaired drivers. Fewer test results indicated impairment in experimental studies compared to impaired drivers in real life when influenced by similar blood concentrations of either ethanol, THC, or benzodiazepines. In addition, a comparable

  2. An experimental trial exploring the impact of continuous transdermal alcohol monitoring upon alcohol consumption in a cohort of male students

    National Research Council Canada - National Science Library

    Neville, Fergus G; Williams, Damien J; Goodall, Christine A; Murer, Jeffrey S; Donnelly, Peter D

    2013-01-01

    .... Participants in Conditions A and B were asked not to consume alcohol for a 14-day period, with those in Condition A additionally being required to wear a continuous transdermal alcohol monitoring anklet...

  3. Effect of H. pylori Infection on Cytokine Profiles and Oxidative Balance in Subjects with Chronic Alcohol Ingestion.

    Directory of Open Access Journals (Sweden)

    Baoge Qu

    Full Text Available Different amounts of ingested alcohol can have distinct effects on the human body. However, there is limited research on chronic alcohol consumption with Helicobacter pylori infection. We sought to investigate the relationship between the cytokine profile, oxidative balance and H. pylori infection in subjects with chronic alcohol consumption. A total of 142 subjects were divided into three groups: 59 subjects with chronic alcohol ingestion and H. pylori infection (group A; 53 subjects with chronic alcohol ingestion without H. pylori infection (group B; and 30 control subjects (group C. The serum levels of CagA, interleukin (IL-10, E-selectin, TNF-α, malondialdehyde (MDA and superoxide dismutase (SOD activity were measured by enzyme-linked immunosorbent assay (ELISA. We found that the ages and serum H. pylori CagA levels among the three groups, as well as both the mean drinking age and the mean daily alcohol consumption between groups A and B, were matched and comparable. Comparing the BMIs among the three groups, the BMI differences were found to be statistically significant (F=3.921, P0.05. Additionally, no differences in the serum CagA levels were found in comparisons among the groups (all P>0.05. The serum IL-10 and E-selectin levels in group A were significantly lower than those in group B (serum IL-10: P0.05. Furthermore, the serum IL-10 and E-selectin levels in group B were significantly higher than those in group C (serum IL-10: P0.05. Although the serum levels of MDA and SOD in groups A and B were slightly lower than those in group C, there were no significant differences among groups (all P>0.05. In conclusion, we believe that H. pylori infection might cause a significant inhibition of certain cytokine profiles in subjects with chronic alcohol ingestion. Moreover, chronically ingested alcohol may exert an adjusted inflammatory effect, but there was no association between H. pylori infection, chronic alcohol consumption and oxidative

  4. Elevated glutathione level does not protect against chronic alcohol mediated apoptosis in recombinant human hepatoma cell line VL-17A over-expressing alcohol metabolizing enzymes--alcohol dehydrogenase and Cytochrome P450 2E1.

    Science.gov (United States)

    Chandrasekaran, Karthikeyan; Swaminathan, Kavitha; Kumar, S Mathan; Chatterjee, Suvro; Clemens, Dahn L; Dey, Aparajita

    2011-06-01

    Chronic consumption of alcohol leads to liver injury. Ethanol-inducible Cytochrome P450 2E1 (CYP2E1) plays a critical role in alcohol mediated oxidative stress due to its ability to metabolize ethanol. In the present study, using the recombinant human hepatoma cell line VL-17A that over-expresses the alcohol metabolizing enzymes-alcohol dehydrogenase (ADH) and CYP2E1; and control HepG2 cells, the mechanism and mode of cell death due to chronic ethanol exposure were studied. Untreated VL-17A cells exhibited apoptosis and oxidative stress when compared with untreated HepG2 cells. Chronic alcohol exposure, i.e., 100 mM ethanol treatment for 72 h caused a significant decrease in viability (47%) in VL-17A cells but not in HepG2 cells. Chronic ethanol mediated cell death in VL-17A cells was predominantly apoptotic, with increased oxidative stress as the underlying mechanism. Chronic ethanol exposure of VL-17A cells resulted in 1.1- to 2.5-fold increased levels of ADH and CYP2E1. Interestingly, the level of the antioxidant GSH was found to be 3-fold upregulated in VL-17A cells treated with ethanol, which may be a metabolic adaptation to the persistent and overwhelming oxidative stress. In conclusion, the increased GSH level may not be sufficient enough to protect VL-17A cells from chronic alcohol mediated oxidative stress and resultant apoptosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. CORRECTION OF MICROCIRCULATORY DISORDERS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH CHRONIC HEART FAILURE PATIENTS

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Combined liver damage in patients with chronic heart failure and non-alcoholic fatty liver disease leads to the formation of pathological hemodynamic types of microcirculation with prevalence of shunt blood flow, nutritional deficiency, that correlated with changes in the functional state of the liver. Using cytoprotector mexicor for 16 weeks as part of the basic treatment of patients with chronic heart failure and non-alcoholic fatty liver disease can correct these microcirculatory disorders, has a beneficial effect on endothelial function, autonomic tone of microvessels, which is accompanied by the positive dynamics of indicators of cytolysis and cholestasis.

  6. Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone Structure or Bone Mechanical Strength

    DEFF Research Database (Denmark)

    Ulhøi, Maiken Parm; Meldgaard, Karoline; Steiniche, Torben

    2017-01-01

    Chronic alcohol abuse (CAA) has deleterious effects on skeletal health. This study examined the impact of CAA on bone with regard to bone density, structure, and strength. Bone specimens from 42 individuals with CAA and 42 individuals without alcohol abuse were obtained at autopsy. Dual-energy X...... wall thickness of trabecular osteons compared to individuals without alcohol abuse. No significant difference was found for bone strength and structure. Conclusion: CAA leads to low bone mass due to a decrease in bone formation but with no destruction of bone architecture nor a decrease in bone...

  7. Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals.

    Science.gov (United States)

    Rowland, Jared A; Stapleton-Kotloski, Jennifer R; Alberto, Greg E; Davenport, April T; Kotloski, Robert J; Friedman, David P; Godwin, Dwayne W; Daunais, James B

    2017-08-01

    Chronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys. Adolescent male vervet monkeys were trained to self-administer ethanol (n=7) or an isocaloric malto-dextrin solution (n=3). Following training, animals received 12 months of free access to ethanol. Animals then underwent RS magnetoencephalography (MEG) and subsequent power spectral analysis of brain activity at 32 bilateral regions of interest associated with the chronic effects of alcohol use. demonstrate localized changes in brain activity in chronic heavy drinkers, including reduced power in the anterior cingulate cortex, hippocampus, and amygdala as well as increased power in the right medial orbital and parietal areas. The current study is the first demonstration of whole-head MEG acquisition in vervet monkeys. Changes in brain activity were consistent with human electroencephalographic studies; however, MEG was able to extend these findings by localizing the observed changes in power to specific brain regions. These regions are consistent with those previously found to exhibit volume loss following chronic heavy alcohol use. The ability to use MEG to evaluate changes in brain activity following chronic ethanol exposure provides a potentially powerful tool to better understand both the acute and chronic effects of alcohol on brain function. Published by Elsevier B.V.

  8. Reversal learning and experimenter-administered chronic intermittent ethanol exposure in male rats.

    Science.gov (United States)

    Badanich, Kimberly A; Fakih, Mackinzie E; Gurina, Tatyana S; Roy, Emalie K; Hoffman, Jessica L; Uruena-Agnes, Adriana R; Kirstein, Cheryl L

    2016-10-01

    Chronic alcohol exposure is associated with impaired decision making skills, cognitive deficits, and poor performance on tasks requiring behavioral flexibility. Although oral routes of alcohol administration are commonly used to examine effects of alcohol on various behaviors in rodents, only a few investigations have used intragastric exposures to evaluate ethanol's effects on behavioral flexibility in the adult rat. The aim of the current series of experiments was to determine if behavioral flexibility impairments would be demonstrated across a variety of procedural factors, including route of administration [intraperitoneal injection (i.p.), intragastric gavage (i.g.)], ethanol dose (3-5 g/kg), number of daily exposures (once/day, twice/day), duration of exposure (2-6 weeks), or length of abstinence (5-7 days). Adult male Sprague-Dawley rats were exposed to chronic intermittent ethanol (CIE) or vehicle and evaluated for behavioral intoxication, blood ethanol concentrations (BEC), and performance on a reversal learning odor discrimination task. While all rats displayed behavioral intoxication and elevated BECs, CIE i.p. rats had prolonged elevation in BECs and made the most errors during the reversal learning task. Unexpectedly, CIE i.g. exposures failed to produce deficits during reversal learning tasks regardless of ethanol dose, frequency/duration of exposure, or length of abstinence. Behavioral flexibility deficits resulting from CIE i.p. exposures may be due to the severity and chronicity of alcohol intoxication. Elucidating the impact of ethanol on behavioral flexibility is critical for developing a better understanding of the behavioral consequences of chronic alcohol exposure.

  9. Chronic Generalized Harassment During College: Influences on Alcohol and Drug Use.

    Science.gov (United States)

    McGinley, Meredith; Rospenda, Kathleen M; Liu, Li; Richman, Judith A

    2015-10-01

    The experience of chronic generalized harassment from others can have a deleterious impact on individuals over time. Specifically, coping resources may be taxed, resulting in the use of avoidant coping strategies such as substance use. However, little is known about the experience of chronic generalized harassment (e.g., verbal hostility, manipulation by others, exclusion from important events) and its impact on substance use in collegiate populations. In the current study, we examined the latent growth of generalized harassment across the transition from high school to college, whether this growth was heterogeneous, and the relationships between latent generalized harassment classifications and substance use. Incoming freshmen students (N = 2890; 58% female; 53% white) at eight colleges in Illinois completed a web survey at five points: fall 2011 (baseline), spring 2012 (T1), fall 2012 (T2), fall 2013 (T3) and fall 2014 (T4). Students were required to be at least 18 years old at baseline, and were compensated with online gift certificates. Two-part latent class growth analysis was implemented in order to examine heterogeneous growth over time. The results supported a two-class solution (infrequent and chronic classes) for generalized harassment. Growth in harassment was characterized by a decrease from baseline through college entry, with a recovery in rates by T3. Members of the chronically harassed class had greater mean generalized harassment over time, and were less likely to report zero instances of harassment experiences. As hypothesized, membership in the chronic class predicted future binge drinking, drinking to intoxication, problems due to alcohol use, and cigarette use, but not marijuana use. Future interventions should focus on providing college students with resources to help cope with distress stemming from persistent generalized harassment from peers, faculty, and other individuals in higher-education settings.

  10. The effects of music genre on young people's alcohol consumption: an experimental observational study.

    Science.gov (United States)

    Engels, Rutger C M E; Poelen, Evelien A P; Spijkerman, Renske; Ter Bogt, Tom

    2012-01-01

    The aim of this study was to test whether exposure to specific music genres in a social drinking setting leads to differences in drinking levels. An observational experimental design was used in which we invited peer groups of young adults into a bar lab, a lab which is furnished like an ordinary, small pub. Between two tasks, people had a break of 50 minutes in which they could order nonalcoholic and alcoholic beverages. During the break, participants were exposed to a specific music genre: popular, hard rock, rap, or classical music. Those groups who were exposed to classical music drank significantly more alcohol than those who were exposed to other music genres. This pattern is quite robust and does not depend on participants' sex or age, drinking habits, own music preference, and relative importance of music in participant's lives. The study's limitations are mentioned.

  11. The proximal effects of acute alcohol use on female aggression: A meta-analytic review of the experimental literature.

    Science.gov (United States)

    Crane, Cory A; Licata, MacKenzie L; Schlauch, Robert C; Testa, Maria; Easton, Caroline J

    2017-02-01

    Experimental research on alcohol-related aggression has focused largely upon male participants, providing only a limited understanding of the proximal effects of acute alcohol use on aggression among females extrapolated from the male literature. The current meta-analysis was undertaken to summarize the effects of alcohol, compared to placebo or no alcohol, on female aggression as observed across experimental investigations. A review of the literature yielded 11 articles and 12 effect sizes for further analysis. The overall effect size of alcohol on female aggression was small and reached statistical significance (d = .17, p = .02, 95% confidence interval [.03, .30]). Meta-analytic examination of the experimental literature indicated that alcohol is a significant factor in female aggression. The overall alcohol-aggression effect was smaller than has been observed among male samples. Additional research is required to evaluate the influence of other factors on alcohol-related aggressive responding among female participants. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Ageing, chronic alcohol consumption and folate are determinants of genomic DNA methylation, p16 promoter methylation and the expression of p16 in the mouse colon

    Science.gov (United States)

    Elder age and chronic alcohol consumption are important risk factors for the development of colon cancer. Each factor can alter genomic and gene-specific DNA methylation. This study examined the effects of aging and chronic alcohol consumption on genomic and p16-specific methylation, and p16 express...

  13. Aging and chronic alcohol consumption are determinants of p16 gene expression, genomic DNA methylation and p16 promoter methylation in the mouse colon

    Science.gov (United States)

    Elder age and chronic alcohol consumption are important risk factors for the development of colon cancer. Each factor can alter genomic and gene-specific DNA methylation. This study examined the effects of aging and chronic alcohol consumption on genomic and p16-specific methylation, and p16 express...

  14. Combined Effect of ADH1B RS1229984, RS2066702 and ADH1C RS1693482/ RS698 Alleles on Alcoholism and Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Réka Tóth

    2011-01-01

    Full Text Available The aim of this study was to analyze the combined effect of the most frequent alcohol dehydrogenase polymorphisms (Arg48His and Arg370Cys in ADH1B, Arg272Gln and Ile350Val in ADH1C on the alcohol use habits, alcohol dependence and chronic liver diseases in Hungary.

  15. An Examination of Problems and Solutions Related to the Chronic "Revolving Door" Alcohol Abuser. DHSS Planning Guideline #1, Task Assignment #1.11. Long-Term Support, Chronic Alcoholism and Other Drug Abuse.

    Science.gov (United States)

    Vick, John W.; Houden, Dorothy

    This report contains recommendations of a Wisconsin Task Assignment Steering Committee created to explore solutions to some significant problems facing adult chronic "revolving-detox-door" alcohol abusers (CRA's), persons with repeated admissions for detoxification services; and to examine the system that serves and funds them. This…

  16. Role of GABAA receptors in alcohol use disorders suggested by chronic intermittent ethanol (CIE) rodent model.

    Science.gov (United States)

    Olsen, Richard W; Liang, Jing

    2017-09-20

    GABAergic inhibitory transmission is involved in the acute and chronic effects of ethanol on the brain and behavior. One-dose ethanol exposure induces transient plastic changes in GABAA receptor subunit levels, composition, and regional and subcellular localization. Rapid down-regulation of early responder δ subunit-containing GABAA receptor subtypes mediating ethanol-sensitive tonic inhibitory currents in critical neuronal circuits corresponds to rapid tolerance to ethanol's behavioral responses. Slightly slower, α1 subunit-containing GABAA receptor subtypes mediating ethanol-insensitive synaptic inhibition are down-regulated, corresponding to tolerance to additional ethanol behaviors plus cross-tolerance to other GABAergic drugs including benzodiazepines, anesthetics, and neurosteroids, especially sedative-hypnotic effects. Compensatory up-regulation of synaptically localized α4 and α2 subunit-containing GABAA receptor subtypes, mediating ethanol-sensitive synaptic inhibitory currents follow, but exhibit altered physio-pharmacology, seizure susceptibility, hyperexcitability, anxiety, and tolerance to GABAergic positive allosteric modulators, corresponding to heightened alcohol withdrawal syndrome. All these changes (behavioral, physiological, and biochemical) induced by ethanol administration are transient and return to normal in a few days. After chronic intermittent ethanol (CIE) treatment the same changes are observed but they become persistent after 30 or more doses, lasting for at least 120 days in the rat, and probably for life. We conclude that the ethanol-induced changes in GABAA receptors represent aberrant plasticity contributing critically to ethanol dependence and increased voluntary consumption. We suggest that the craving, drug-seeking, and increased consumption in the rat model are tied to ethanol-induced plastic changes in GABAA receptors, importantly the development of ethanol-sensitive synaptic GABAA receptor-mediating inhibitory currents

  17. Alcohol Consumption in Relation to Risk and Severity of Chronic Widespread Pain: Results From a UK Population-Based Study.

    Science.gov (United States)

    Macfarlane, Gary J; Beasley, Marcus

    2015-09-01

    To determine whether the reported level of alcohol consumption is associated with the likelihood of reporting chronic widespread pain (CWP) and, among persons with CWP, the associated disability. In a population-based study in 2 areas of the UK, participants self-completed a postal questionnaire. They were classified according to whether they met the American College of Rheumatology definition of CWP and whether the pain was disabling (Chronic Pain Grade III or IV). They reported their usual level of alcohol consumption. Potential confounding factors on which information was available included age, sex, cigarette smoking, employment status, self-reported weight and height, and level of deprivation. A total of 13,574 persons participated (mean age 55 years, 57% women) of whom 2,239 (16.5%) had CWP; 28% reported never regularly consuming alcohol, 28% reported consuming up to 5 units/week, 20% reported 6-10 units/week, and 24% reported >10 units/week. Among persons with CWP, disability was strongly linked to level of alcohol consumption. Prevalence of disability decreased with increasing alcohol consumption up to 35 units/week (odds ratio [OR]21-35 units alcohol/week versus never drinkers 0.33 [95% confidence interval (95% CI) 0.19-0.58]) adjusted for confounders. A similar relationship was found between reporting CWP and level of alcohol consumption (adjusted OR21-35 units alcohol/week versus never drinkers 0.76 [95% CI 0.61-0.94]). This study has demonstrated strong associations between level of alcohol consumption and both CWP and related disabilities. However, the available evidence does not allow us to conclude that the association is causal. The strength of the associations means that specific studies to examine this potential relationship are warranted. © 2015 The Authors. Arthritis Care & Research is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

  18. Stress and consumption of alcohol in humans with a Type 1 family history of alcoholism in an experimental laboratory setting.

    Science.gov (United States)

    Gordh, Anna H V Söderpalm; Brkic, Sejla; Söderpalm, Bo

    2011-10-01

    This paper investigates how stress interacts with alcohol consumption in subjects with a family history of alcoholism. One mechanism for increases in alcohol intake may be that stress alters the subjective effects produced by the drug. 58 healthy volunteers, divided into two groups of family history positive (FHP) and two groups of family history negative (FHN) participated in two laboratory sessions, in which they performed in one out of two sessions a stress task. Then subjects were allowed to choose up to six additional drinks of ethanol or placebo depending on which session they were randomly assigned to start with. It was found that FHP subjects increased their consumption of alcohol after stress. It is possible that both stress and alcohol specifically exaggerate the feelings of the reward in the FHP individuals in such way that it may increase the likelihood of consuming more alcohol. Copyright © 2011. Published by Elsevier Inc.

  19. Hypokalemic Paralysis Complicated by Concurrent Hyperthyroidism and Chronic Alcoholism: A Case Report.

    Science.gov (United States)

    Tsai, Ming-Hsien; Lin, Shih-Hua; Leu, Jyh-Gang; Fang, Yu-Wei

    2015-09-01

    Thyrotoxic periodic paralysis (TPP) is characterized by the presence of muscle paralysis, hypokalemia, and hyperthyroidism. We report the case of a young man with paralysis of the lower extremities, severe hypokalemia, and concurrent hyperthyroidism. TPP was suspected; therefore, treatment consisting of judicious potassium (K+) repletion and β-blocker administration was initiated. However, urinary K+ excretion rate, as well as refractoriness to treatment, was inconsistent with TPP. Chronic alcoholism was considered as an alternative cause of hypokalemia, and serum K+ was restored through vigorous K repletion and the addition of K+ -sparing diuretics. The presence of thyrotoxicosis and hypokalemia does not always indicate a diagnosis of TPP. Exclusion of TPP can be accomplished by immediate evaluation of urinary K+ excretion, acid-base status, and the amount of potassium chloride required to correct hypokalemia at presentation.

  20. Central pontine myelinolysis in a chronic alcoholic: A clinical and brain magnetic resonance imaging follow-up

    Directory of Open Access Journals (Sweden)

    Dujmović Irena

    2013-01-01

    Full Text Available Introduction. Central pontine myelinolysis (CPM is a noninflammatory, demyelinating lesion usually localised in the basis pontis. Chronic alcoholism is frequently associated with this condition which may have a variable clinical outcome. Until now, brain magnetic resonance imaging (MRI follow-up in alcoholic CPM cases after alcohol withdrawal has been rarely described. Case report. We reported a 30- year-old male with a 12-year history of alcohol abuse, who presented with inability to stand and walk, nausea, vomiting and somnolence. Neurological examination revealed: impared fixation on lateral gaze, dysarthria, mild spastic quadriparesis, truncal and extremity ataxia, sock-like hypesthesia and moderate decrease in vibration sense in legs. Brain MRI showed a trident-shaped non-enhancing pontine lesion highly suggestive of CPM. After an eight-month alcoholfree follow-up period, the patient’s clinical status significantly improved, while the extent of MRI pontine lesion was merely slightly reduced. Conclusion. The presented case demonstrates that CPM in chronic alcoholics may have a benign clinical course after alcohol withdrawal, which is not necessarily associated with the reduction of lesions on brain MRI. [Projekat Ministarstva nauke Republike Srbije, br. 175031

  1. Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with lamotrigine.

    Science.gov (United States)

    Zalewska-Kaszubska, Jadwiga; Bajer, Bartosz; Gorska, Dorota; Andrzejczak, Dariusz; Dyr, Wanda; Bieńkowski, Przemysław

    2015-02-01

    Several recent studies have indicated that lamotrigine, similarly to other antiepileptic drugs, may be useful in the therapy of alcohol dependence. The rationale for using lamotrigine in the treatment of alcohol addiction is based on its multiple mechanisms of action which include inhibition of voltage-sensitive sodium channels, modulation voltage-gated calcium currents and transient potassium outward current. However, the known mechanism of lamotrigine does not fully explain its efficacy in alcohol addiction therapy. For this reason we have decided to examine the effect of lamotrigine on the opioid system. Our previous studies showed that topiramate and levetiracetam (antiepileptic drugs) as well as the most effective drugs in alcohol addiction therapy i.e. naltrexone and acamprosate, when given repeatedly, all increased plasma beta endorphin (an endogenous opioid peptide) level, despite operating through different pharmacological mechanisms. It is known that low beta-endorphin level is often associated with alcohol addiction and also that alcohol consumption elevates the level of this peptide. This study aims to assess the effect of repeated treatment with lamotrigine on voluntary alcohol intake and beta-endorphin plasma level in alcohol preferring rats (Warsaw high preferring (WHP) rats). We observed a decrease in alcohol consumption in rats treated with lamotrigine. However we didn't observe significant changes in beta-endorphin level during withdrawal of alcohol, which may indicate that the drug does not affect the opioid system. We suppose that lamotrigine may be useful in alcohol dependence therapy and presents a potential area for further study. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

    Directory of Open Access Journals (Sweden)

    S.Q. Cui

    2015-06-01

    Full Text Available We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each. The model group received 60% (v/v ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N and microglia (by Ib1 were conducted. Glutamic acid (Glu and gamma amino butyric acid (GABA in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC, and tumor necrosis factor (TNF-α and interleukin (IL-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05 by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01, and neurons were reduced only in the hippocampal dentate gyrus (P<0.01 in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05, and Glu/GABA, TNF-α, and IL-1β increased (P<0.01 with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

  3. Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems.

    Science.gov (United States)

    Yeung, Ellen W; Craggs, Jason G; Gizer, Ian R

    2017-11-01

    Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence has suggested that neuroadaptive processes characterized by reward deficit and stress surfeit are involved in the development of AUD and pain chronification. Neurological data suggest that shared genetic architecture associated with the reward and stress systems may contribute to the comorbidity of AUD and CP. This monograph first delineates the prevailing theories of the development of AUD and pain chronification focusing on the reward and stress systems. It then provides a brief summary of relevant neurological findings followed by an evaluation of evidence documented by molecular genetic studies. Candidate gene association studies have provided some initial support for the genetic overlap between AUD and CP; however, these results must be interpreted with caution until studies with sufficient statistical power are conducted and replications obtained. Genomewide association studies have suggested a number of genes (e.g., TBX19, HTR7, and ADRA1A) that are either directly or indirectly related to the reward and stress systems in the AUD and CP literature. Evidence reviewed in this monograph suggests that shared genetic liability underlying the comorbidity between AUD and CP, if present, is likely to be complex. As the advancement in molecular genetic methods continues, future studies may show broader central nervous system involvement in AUD-CP comorbidity. Copyright © 2017 by the Research Society on Alcoholism.

  4. Evaluation of the brachial artery endothelial function in chronic alcohol consumption among males by high-frequency ultrasonography.

    Science.gov (United States)

    Luo, Runlan; Shen, Jiaqi; Zhou, Qiao; Liu, Yue; Li, Guangsen

    2017-02-01

    There is evidence suggesting that different volumes of chronic alcohol consumption have different effects on the endothelium. Therefore, using high-frequency ultrasonography, we evaluate the effects of the different volume and duration of alcohol intake on brachial artery endothelial function in chronic drinkers. Ninety-two male chronic episodic alcoholics were grouped by alcohol intake amount and duration: mild (group B, n=30); ≤90 mg ethanol daily, 3-5 days/wk for 5-8 years; moderate (group C, n=30); 90-150 mg ethanol daily, 3-5 days/wk for 9-20 years; and severe (group D, n=32); ≥150 mg ethanol daily, 6-7 days/wk for more than 10 years. Thirty male nondrinkers were recruited as the control group A. High-frequency ultrasonography was used to measure brachial artery diameter during rest, during reactive hyperemia and following the administration of nitroglycerin. Endothelial-dependent brachial artery flow-mediated dilatation (FMD) and endothelial-independent brachial artery nitrate-mediated dilatation (NMD) were calculated. Flow-mediated dilatation values for group C and D were significantly lower than those for group A and B (VC =7.63±0.22, VD =5.85±0.23 vs VA =13.35±0.35, VB =12.81±0.36, Pconsumption caused endothelial dysfunction, even damaging vascular smooth muscle cells in cases of heavy alcohol consumption, while abstinence and chronic mild alcoholics caused no effect on endothelial function. © 2016, Wiley Periodicals, Inc.

  5. Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats.

    Science.gov (United States)

    Prkacin, I; Aralica, G; Perovic, D; Separovic, J; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Ziger, T; Anic, T; Sikiric, P; Seiwerth, S; Staresinic, M; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sjekavica, I; Sebecic, B; Boban-Blagaic, A; Ivasovic, Z

    2001-01-01

    Unlike severe gastric damage acutely induced by ethanol administration in rat, the ulcerogenic effect of chronic alcohol administration (3.03 g/kg b.w. or 7.28 g/kg b.w.) given in drinking water, producing liver lesions and portal hypertension, is far less investigated. Therefore, focus was on the antiulcer effect of the gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in variety of gastrointestinal lesions models (10 microg or 10 ng/kg b.w. i.p. or i.g.), ranitidine (10 mg/kg b.w. i.g.) and propranol (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). They were given once daily (1) throughout 10 days preceding alcohol consumption, (2) since beginning of alcohol drinking till the end of the study, (3) throughout the last month of alcohol consumption, 2 months after alcohol drinking had been initiated. Gastric lesions were assessed, at the end of 3 months drinking [(1), (2)] or with respect to therapeutic effect of medication before medication or at the end of therapy. Pentadecapeptide BPC 157, ranitidine and propranolol may prevent gastric lesion development if given prophylactically, before alcohol drinking. Likewise, they attenuate the lesion appearance given once daily throughout the drinking period. Importantly, when given therapeutically, they may antagonize otherwise pertinent lesion presence in stomach mucosa of the drinking rats. Thus, these results demonstrate that pentadecapeptide BPC 157, ranitidine and propranol may prevent, attenuate or reverse the gastric lesions appearance in chronically alcohol drinking rats, and may be used for further therapy, while the other studies showed that their effect (except to ranitidine) is parallel with their beneficial effect on liver lesion and portal hypertension.

  6. Related Changes of Autonomic Ganglia and Respiratory Compartments of Lungs in Case of Chronic Alcohol Intoxication in Experiments with Rats

    Directory of Open Access Journals (Sweden)

    Volkov Aleksandr Vladimirovich

    2014-09-01

    Full Text Available The article deals with description of morphological alterations in lungs and their autonomic ganglia due to chronic alcohol intoxication caused by compulsory ethanol ingesting in Wistar rats. Progressive decrease of air content, superficial density of bronchial and alveolar epithelia, and the increase of quantitative density of bronchial and alveolar macrophages became quantitative morphological evidence of chronic lung injury. At the same time, in autonomic ganglia of lungs the volume fraction and quantitative density of neurons decreased dramatically and the characteristics of neurons in radial morphometry were altered. The quantitative density of glial cells and glia/neuron ratio were increased. The total loss of neurons in ganglia reached 7 % to the 60th day of experiment, the signs of compensatory reactions were revealed simultaneously. These peculiarities can particularly explain the mechanisms of chronic lung pathology in late stages of alcohol disease.

  7. Alcohol

    Science.gov (United States)

    ... addicted, there are some downsides to drinking: The punishment is severe. Teens who drink put themselves at ... treatment centers help a person gradually overcome the physical and psychological dependence on alcohol. previous continue What ...

  8. Chronic alcohol abuse in men alters bone mechanical properties by affecting both tissue mechanical properties and microarchitectural parameters.

    Science.gov (United States)

    Cruel, M; Granke, M; Bosser, C; Audran, M; Hoc, T

    2017-06-01

    Alcohol-induced secondary osteoporosis in men has been characterized by higher fracture prevalence and a modification of bone microarchitecture. Chronic alcohol consumption impairs bone cell activity and results in an increased fragility. A few studies highlighted effects of heavy alcohol consumption on some microarchitectural parameters of trabecular bone. But to date and to our knowledge, micro- and macro-mechanical properties of bone of alcoholic subjects have not been investigated. In the present study, mechanical properties and microarchitecture of trabecular bone samples from the iliac crest of alcoholic male patients (n=15) were analyzed and compared to a control group (n=8). Nanoindentation tests were performed to determine the tissue's micromechanical properties, micro-computed tomography was used to measure microarchitectural parameters, and numerical simulations provided the apparent mechanical properties of the samples. Compared to controls, bone tissue from alcoholic patients exhibited an increase of micromechanical properties at tissue scale, a significant decrease of apparent mechanical properties at sample scale, and significant changes in several microarchitectural parameters. In particular, a crucial role of structure model index (SMI) on mechanical properties was identified. 3D microarchitectural parameters are at least as important as bone volume fraction to predict bone fracture risk in the case of alcoholic patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Behavioral effects of the combined use of alcohol and energy drinks on alcohol hangover in an experimental mice model.

    Science.gov (United States)

    Asorey, Lucas G; Carbone, Silvia; Gonzalez, Bárbara J; Cutrera, Rodolfo A

    2018-02-01

    In last few years it has been a significant increase in the consumption of alcohol combined with energy drink. The aim of this work was to study the effect of this mixture in motor and affective behaviors during an alcohol hangover episode. Male Swiss mice received one of the following treatments: saline + sucrose; saline + energy drink; ethanol + sucrose; ethanol + energy drink. Ethanol dose was 3.8 g/kg BW (i.p.) and energy drink dose was 18 ml/kg BW (gavage) at ZT1 (8 am) (ZT: Zeitgeber time; ZT0: 7 am; lights on). The behavioral tests used were tight rope test to determine motor coordination; hanging wire test to study muscular strength; elevated plus maze and open field tests to evaluate anxiety like-behavior and locomotor activity. Tests were carried out at basal point that matched with lights onset and every 6 h up to 18 h after treatments. Hangover onset was established at ZT7 when blood alcohol concentration (BAC) was almost zero. Our results showed that the mixture of alcohol and energy drink altered significantly motor skills. Specifically, a significant decrease was observed in the performance of the animals in the tightrope and hanging wire tests in groups treated with the mixture of alcohol and energy drink. A significant impairment in the anxiety-like behavior was observed mainly at the beginning of alcohol hangover. These findings suggest that energy drink added to alcohol extends motor disabilities observed during an alcohol hangover episode in comparison with animals that received alcohol alone. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Detection of new human metabolic urinary markers in chronic alcoholism and their reversal by aqueous extract of Tinospora cordifolia stem.

    Science.gov (United States)

    Mittal, Ashwani; Dabur, Rajesh

    2015-05-01

    We have studied urine metabolic signature of chronic alcoholism (CA) before and after treatment with an Ayurvedic drug Tinospora cordifolia aqueous extract (TCE). Urinary metabolites of chronic alcoholics and apparently healthy subjects were profiled using HPLC-Q-TOF-MS. Discrimination models from the initial data sets were able to correctly assign the unknown samples to the CA, treated or healthy groups in validation sets with r(2) > 0.98. Metabolic signature in CA patients include changed tryptophan, fatty acids and pyrimidines metabolism. Several novel biomarkers of alcoholism were observed in urine for the first time which includes, 5-hydroxyindole, phenylacetic acid, picolinic acid, quinaldic acid, histidine, cystathionine, riboflavin, tetrahydrobiopterin and chenodeoxyglycocholic acid, in addition to previously reported biomarkers. Treatment of CA with TCE reverted the levels of most of the biomarkers except tetrahydrobiopterin levels. These results suggested that the measurement of these urine metabolites could be used as a non-invasive diagnostic method for the detection of CA. As TCE treatment significantly reversed the affected pathways without any side effect. Overall, the present data depicts that TCE may be used either alone or adjunct in reducing alcohol-induced disorders. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  11. Alcoholism (image)

    Science.gov (United States)

    Alcoholism is a chronic illness marked by dependence on alcohol consumption that interferes with physical or mental health, and social, family or job responsibilities. This addiction can lead to liver, circulatory and neurological problems. Pregnant women who ...

  12. Disposition of d-penicillamine, a promising drug for preventing alcohol-relapse. Influence of dose, chronic alcohol consumption and age: studies in rats.

    Science.gov (United States)

    Orrico, Alejandro; Martí-Prats, Lucía; Cano-Cebrián, M José; Polache, Ana; Zornoza, Teodoro; Granero, Luis

    2014-07-01

    Pharmacokinetic studies concerning d-penicillamine (an acetaldehyde sequestering agent) are scarce and have not evaluated the influence of chronic ethanol consumption and age on its disposition. Since recent preclinical studies propose d-penicillamine as a promising treatment for alcohol relapse, the main aim of the present work was to evaluate the influence of these two factors on d-penicillamine disposition in order to guide future clinical studies on the anti-relapse efficacy of this drug in alcoholism. Additionally, the effect of the administered dose was also evaluated. To this end, three studies were carried out. Study 1 assessed the influence of dose on d-penicillamine disposition, whereas studies 2 and 3 evaluated, respectively, the influence of chronic alcohol consumption and age. Rapid intravenous administrations of 2, 10 and 30 mg/kg of d-penicillamine were performed using young or adult ethanol-naïve rats or adult ethanol-experienced (subjected to a long-term ethanol self-administration protocol) rats. Pharmacokinetic parameters were derived from the biexponential model. Statistical analysis of CL, normalized AUC0 (∞) , V1 and k10 revealed that disposition, in the range plasma concentrations assayed, is non-linear both in young ethanol-naïve and in adult ethanol-experienced rats. Notably, no significant changes in t1/2 were detected. Chronic ethanol consumption significantly reduced CL values by 35% without affecting t1/2 . d-Penicillamine disposition was equivalent in young and adult animals. In conclusion, although DP pharmacokinetics is non-linear, the lack of significant alterations of the t1/2 would potentially simplify the clinical use of this drug. Chronic consumption of ethanol also alters d-penicillamine disposition but, again, does not modify t1/2. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats.

    Science.gov (United States)

    Lang, Charles H; Korzick, Donna H

    2014-01-01

    The purpose of this study was to assess whether the deleterious effect of chronic alcohol consumption differs in adult and aged female rats. To address this aim, adult (4 mo) and aged (18 mo) F344 rats were fed a nutritionally complete liquid diet containing alcohol (36% total calories) or an isocaloric isonitrogenous control diet for 20 wk. Cardiac structure and function, assessed by echocardiography, as well as myocardial protein synthesis and proteolysis did not differ in either alcohol- versus control-fed adult rats or in adult versus aged control-fed rats. In contrast, cardiac function was impaired in alcohol-fed aged rats compared with age-matched control rats. Additionally, alcohol feeding decreased cardiac protein synthesis that was associated with decreased phosphorylation of 4E-BP1 and S6K1. This reduction in mammalian target of rapamycin (mTOR) kinase activity was associated with reduced eIF3f and binding of both Raptor and eIF4G to eIF3. Proteasome activity was increased in alcohol-fed aged rats with a coordinate elevation in the E3 ligases atrogin-1 and muscle RING-finger protein-1 (MuRF1). These changes were associated with increased regulated in development and DNA damage response 1 (REDD1) and phosphorylation of AMP-activated protein kinase (AMPK) but no increase in AKT or forkhead transcription factor (FOXO)3 phosphorylation. Finally, markers of autophagy (e.g., LC3B, Atg7, Atg12) and TNF-α were increased to a greater extent in alcohol-fed aged rats. These data demonstrate that aged female rats exhibit an enhanced sensitivity to alcohol compared with adult animals. Our data are consistent with a model whereby alcohol increases proteolysis via FOXO-independent increase in atrogin-1, which degrades eIF3f and therefore impairs formation of a functional preinitiation complex and protein synthesis.

  14. Chronic alcohol consumption leads to neurochemical changes in the nucleus accumbens that are not fully reversed by withdrawal.

    Science.gov (United States)

    Pereira, Pedro A; Neves, João; Vilela, Manuel; Sousa, Sérgio; Cruz, Catarina; Madeira, M Dulce

    2014-01-01

    Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and the possible involvement of nerve growth factor (NGF) in mediating the effects of ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats subsequently deprived from ethanol during 2months were used to estimate the total number and the somatic volume of NPY and cholinergic interneurons, and the numerical density of cholinergic varicosities in the NAc. The tissue content of choline acetyltransferase (ChAT) and catecholamines were also determined. The number of NPY interneurons increased during alcohol ingestion and returned to control values after withdrawal. Conversely, the number and the size of cholinergic interneurons, and the amount of ChAT were unchanged in ethanol-treated and withdrawn rats, but the density of cholinergic varicosities was reduced by 50% during alcohol consumption and by 64% after withdrawal. The concentrations of dopamine and norepinephrine were unchanged both during alcohol consumption and after withdrawal. The administration of NGF to withdrawn rats significantly increased the number of NPY-immunoreactive neurons, the size of cholinergic neurons and the density of cholinergic varicosities. Present data show that chronic alcohol consumption leads to long-lasting neuroadaptive changes of the cholinergic innervation of the NAc and suggest that the cholinergic system is a potential target for the development of therapeutic strategies in alcoholism and abstinence. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Alcoholic hallucinosis.

    Science.gov (United States)

    Bhat, Pookala S; Ryali, Vssr; Srivastava, Kalpana; Kumar, Shashi R; Prakash, Jyoti; Singal, Ankit

    2012-07-01

    Alcoholic hallucinosis is a rare complication of chronic alcohol abuse characterized by predominantly auditory hallucinations that occur either during or after a period of heavy alcohol consumption. Bleuler (1916) termed the condition as alcohol hallucinosis and differentiated it from Delirium Tremens. Usually it presents with acoustic verbal hallucinations, delusions and mood disturbances arising in clear consciousness and sometimes may progress to a chronic form mimicking schizophrenia. One such case with multimodal hallucinations in a Defence Service Corps soldier is presented here.

  16. Alcoholic hallucinosis

    OpenAIRE

    Pookala S Bhat; VSSR Ryali; Kalpana Srivastava; Shashi R Kumar; Jyoti Prakash; Ankit Singal

    2012-01-01

    Alcoholic hallucinosis is a rare complication of chronic alcohol abuse characterized by predominantly auditory hallucinations that occur either during or after a period of heavy alcohol consumption. Bleuler (1916) termed the condition as alcohol hallucinosis and differentiated it from Delirium Tremens. Usually it presents with acoustic verbal hallucinations, delusions and mood disturbances arising in clear consciousness and sometimes may progress to a chronic form mimicking schizophrenia. One...

  17. Using Experimental Paradigms to Examine Alcohol's Role in Men's Sexual Aggression: Opportunities and Challenges in Proxy Development.

    Science.gov (United States)

    Abbey, Antonia; Wegner, Rhiana

    2015-08-01

    The goals of this article are to review the major findings from alcohol administration studies that use sexual aggression proxies and to encourage additional experimental research that evaluates hypotheses about the role of alcohol in the etiology of men's sexual aggression. Experiments allow participants to be randomly assigned to drink conditions, therefore ensuring that any differences between drinkers and nondrinkers can be attributed to their alcohol consumption. One of the biggest challenges faced by experimental researchers is the identification of valid operationalizations of key constructs. The tension between internal and external validity is particularly problematic for violence researchers because they cannot allow participants to engage in the target behavior in the laboratory. The strengths and limitations associated with written vignettes, audiotapes, videotapes, and confederate proxies for sexual aggression are described. Suggestions are made for future research to broaden the generalizability of the findings from experimental research. © The Author(s) 2015.

  18. Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research.

    Science.gov (United States)

    Le Berre, Anne-Pascale; Fama, Rosemary; Sullivan, Edith V

    2017-08-01

    Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions. Despite evidence for differences in recovery levels of selective cognitive processes, certain deficits can persist even with prolonged sobriety. Herein is presented a review of alcohol-related cognitive impairments affecting component processes of executive functioning, memory, and the recently investigated cognitive domains of metamemory, social cognition, and emotional processing; also considered are trajectories of cognitive recovery with abstinence. Finally, in the spirit of critical review, limitations of current knowledge are noted and avenues for new research efforts are proposed that focus on (i) the interaction among emotion-cognition processes and identification of vulnerability factors contributing to the development of emotional and social processing deficits and (ii) the time line of cognitive recovery by tracking alcoholism's dynamic course of sobriety and relapse. Knowledge about the heterochronicity of cognitive recovery in alcoholism has the potential of indicating at which points during recovery intervention may be most beneficial. Copyright © 2017 by the Research Society on Alcoholism.

  19. Experimentally induced aggressiveness in adult children of alcoholics (ACOAs): preliminary behavioral and neuroendocrine findings.

    Science.gov (United States)

    Gerra, G; Zaimovic, A; Sartori, R; Raggi, M A; Bocchi, C; Zambelli, U; Timpano, M; Zanichelli, V; Delsignore, R; Brambilla, F

    1999-11-01

    This study was conducted to determine the nature of the reaction of nonalcoholic adult children of alcoholic (ACOA) fathers to the experimental induction of aggression. Of particular interest was the relationship between biochemical factors and personality traits during a stressful event experienced by persons at risk for alcoholism. Aggression was induced by a modified free-operant procedure in 14 ACOA and 14 non-ACOA subjects between 18 and 19 years of age with men and women represented in equal numbers. Neurotransmitter-hormonal assays from blood drawn immediately before, and 20 and 30 minutes after, starting the test included norepinephrine (NE), epinephrine (EPI), prolactin (PRL), growth hormone (GH) and cortisol (Cort). Personality traits were assessed by the Minnesota Multiphasic Personality Inventory (MMPI) Tridimensional Personality Questionnaire (TPQ) and the Buss-Durkee Hostility Inventory (BDHI). During the aggression induction session, ACOAs gained (F = 4.6, 1/13 df, p aggressiveness among ACOAs. Higher baseline plasma levels of Cort (F = 9.8, 1/13 df, p aggression in ACOAs in association with monoaminergic and endocrine changes.

  20. Changes in scleral collagen organization in murine chronic experimental glaucoma.

    Science.gov (United States)

    Pijanka, Jacek K; Kimball, Elizabeth C; Pease, Mary E; Abass, Ahmed; Sorensen, Thomas; Nguyen, Thao D; Quigley, Harry A; Boote, Craig

    2014-09-16

    The organization of scleral collagen helps to determine the eye's biomechanical response to intraocular pressure (IOP), and may therefore be important in glaucoma. This study provides a quantitative assessment of changes in scleral collagen fibril organization in bead-induced murine experimental glaucoma. Wide-angle X-ray scattering was used to study the effect of bead-induced glaucoma on posterior scleral collagen organization in one eye of 12 CD1 mice, with untreated fellow eyes serving as controls. Three collagen parameters were measured: the local preferred fibril directions, the degree of collagen anisotropy, and the total fibrillar collagen content. The mouse sclera featured a largely circumferential orientation of fibrillar collagen with respect to the optic nerve head canal. Localized alteration to fibril orientations was evident in the inferior peripapillary sclera of bead-treated eyes. Collagen anisotropy was significantly (Pglaucoma in mice, and potentially in human glaucoma. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  1. Fate of ethanol during cooking of liquid foods prepared with alcoholic beverages: Theory and experimental studies.

    Science.gov (United States)

    Snitkjær, Pia; Ryapushkina, Julia; Skovenborg, Erik; Astrup, Arne; Bech, Lene Mølskov; Jensen, Morten Georg; Risbo, Jens

    2017-09-01

    To obtain an understanding of the ethanol loss during cooking of liquid foods containing alcoholic beverages, ethanol concentration was measured as a function of time and remaining volume in meat stocks prepared with wine and beer. A mathematical model describing the decline in volatile compounds during heating of simple liquid foods was derived. The experimental results and the model show that concentration of ethanol at any given time is determined by the initial concentration and a power law function of the remaining volume fraction. The power law function is found to be independent of factors like pot dimensions and temperature. When using a lid to cover the pot during cooking, the model was still valid but the ethanol concentrations decreased more steeply, corresponding to a higher exponent. The results provide a theoretical and empirical guideline for predicting the ethanol concentration in cooked liquid foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The occurrence and significance of fibronectin in livers from chronic alcoholics. An immunohistochemical study of early alcoholic liver injury

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Christoffersen, P

    1988-01-01

    The occurrence and distribution of fibronectin (FN) was assessed by an immunoperoxidase technique in liver biopsies from alcoholics without and with acinar zone 3 fibrosis of varying degrees. Increased amounts of FN was found diffusely in zone 3 areas with a perisinusoidal and pericellular...... localization. FN was closely correlating to the pattern of fibrosis but increased amounts of FN could also be seen in biopsies without fibrosis as visualized in Picro-Sirius stained sections. There was no topographical relationship to liver cells with fatty changes, Mallory bodies or to alcoholic hepatitis....... It is made probable that FN is of significance in the development of early liver fibrosis in alcoholics and that FN may act as a chemotactic factor for collagen producing cells and as a skeleton for the new collagen formation....

  3. Chronic alcohol consumption from adolescence-to-adulthood in mice--hypothalamic gene expression changes in the dilated cardiomyopathy signaling pathway.

    Science.gov (United States)

    Zou, Hong; Wang, Ke; Gao, Yang; Song, Huaiguang; Xie, Qinglian; Jin, Meilei; Zhao, Guoping; Xiao, Huasheng; Yu, Lei

    2014-05-09

    Adolescence is a developmental stage vulnerable to alcohol drinking-related problems and the onset of alcoholism. Hypothalamus is a key brain region for food and water intake regulation, and is one of the alcohol-sensitive brain regions. However, it is not known what would be the alcohol effect on hypothalamus following adolescent alcohol intake, chronically over the adolescent development, at moderate levels. We employed a paradigm of chronic moderate alcohol intake from adolescence-to-adulthood in mice, and analyzed the alcohol effect on both behavioral and hypothalamic gene expression changes. A total of 751 genes were found and subjected to pathway analysis. The dilated cardiomyopathy (DCM) pathway was identified. The changes of ten genes under this pathway were further verified using RT-PCR. Chronic alcohol consumption during adolescence, even at moderate levels, led to a decrease of motor activity in mice, and also a concerted down regulation of signaling pathway initiating factor (SPIF) genes in the DCM signaling pathway, including β1-adrenergic receptor (Adrb1), Gs protein (Gnas), adenylyl cyclase 1 (Adcy1), and dihydropyridine receptor/L-type calcium channel (Cacna1d). These findings suggest that adolescent alcohol intake may trigger gene expression changes in the CNS that parallel those found in the dilated cardiomyopathy signaling pathway. If such effects also take place in humans, our findings would serve as a warning against alcohol intake in youth, such as by teens and/or college students.

  4. IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

    Science.gov (United States)

    Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

    2016-03-01

    Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

  5. Chronic alcohol alters dendritic spine development in neurons in primary culture.

    Science.gov (United States)

    Romero, Ana M; Renau-Piqueras, Jaime; Pilar Marin, M; Timoneda, Joaquin; Berciano, Maria T; Lafarga, Miguel; Esteban-Pretel, Guillermo

    2013-11-01

    Dendritic spines are specialised membrane protrusions of neuronal dendrites that receive the majority of excitatory synaptic inputs. Abnormal changes in their density, size and morphology have been associated with various neurological and psychiatric disorders, including those deriving from drug addiction. Dendritic spine formation, morphology and synaptic functions are governed by the actin cytoskeleton. Previous in vivo studies have shown that ethanol alters the number and morphology of spines, although the mechanisms underlying these alterations remain unknown. It has also been described how chronic ethanol exposure affects the levels, assembly and cellular organisation of the actin cytoskeleton in hippocampal neurons in primary culture. Therefore, we hypothesised that the ethanol-induced alterations in the number and shape of dendritic spines are due to alterations in the mechanisms regulating actin cytoskeleton integrity. The results presented herein show that chronic exposure to moderate levels of alcohol (30 mM) during the first 2 weeks of culture reduces dendritic spine density and alters the proportion of the different morphologies of these structures in hippocampal neurons, which affects the formation of mature spines. Apparently, these effects are associated with an increase in the G-actin/F-actin ratio due to a reduction of the F-actin fraction, leading to changes in the levels of the different factors regulating the organisation of this cytoskeletal component. The data presented herein indicate that these effects occur between weeks 1 and 2 of culture, an important period in dendritic spines development. These changes may be related to the dysfunction in the memory and learning processes present in children prenatally exposed to ethanol.

  6. Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone Structure or Bone Mechanical Strength.

    Science.gov (United States)

    Ulhøi, Maiken Parm; Meldgaard, Karoline; Steiniche, Torben; Odgaard, Anders; Vesterby, Annie

    2017-01-01

    Chronic alcohol abuse (CAA) has deleterious effects on skeletal health. This study examined the impact of CAA on bone with regard to bone density, structure, and strength. Bone specimens from 42 individuals with CAA and 42 individuals without alcohol abuse were obtained at autopsy. Dual-energy X-ray absorptiometry (DEXA), compression testing, ashing, and bone histomorphometry were performed. Individuals with CAA had significantly lower bone mineral density (BMD) in the femoral neck and significantly lower bone volume demonstrated by thinner trabeculae, decreased extent of osteoid surfaces, and lower mean wall thickness of trabecular osteons compared to individuals without alcohol abuse. No significant difference was found for bone strength and structure. CAA leads to low bone mass due to a decrease in bone formation but with no destruction of bone architecture nor a decrease in bone strength. It is questionable whether this per se increases fracture risk. © 2016 American Academy of Forensic Sciences.

  7. Chronic Sleep Restriction Disrupts Sleep Homeostasis and Behavioral Sensitivity to Alcohol by Reducing the Extracellular Accumulation of Adenosine

    Science.gov (United States)

    Clasadonte, Jerome; McIver, Sally R.; Schmitt, Luke I.; Halassa, Michael M.

    2014-01-01

    Sleep impairments are comorbid with a variety of neurological and psychiatric disorders including depression, epilepsy, and alcohol abuse. Despite the prevalence of these disorders, the cellular mechanisms underlying the interaction between sleep disruption and behavior remain poorly understood. In this study, the impact of chronic sleep loss on sleep homeostasis was examined in C57BL/6J mice following 3 d of sleep restriction. The electroencephalographic power of slow-wave activity (SWA; 0.5–4 Hz) in nonrapid eye movement (NREM) sleep and adenosine tone were measured during and after sleep restriction, and following subsequent acute sleep deprivation. During the first day of sleep restriction, SWA and adenosine tone increased, indicating a homeostatic response to sleep loss. On subsequent days, SWA declined, and this was accompanied by a corresponding reduction in adenosine tone caused by a loss of one source of extracellular adenosine. Furthermore, the response to acute sleep deprivation (6 h) was significantly attenuated in sleep-restricted mice. These effects were long-lasting with reduced SWA and adenosine tone persisting for at least 2 weeks. To investigate the behavioral consequences of chronic sleep restriction, sensitivity to the motor-impairing effects of alcohol was also examined. Sleep-restricted mice were significantly less sensitive to alcohol when tested 24 h after sleep restriction, an effect that persisted for 4 weeks. Intracerebroventricular infusion of an adenosine A1 receptor antagonist produced a similar decrease in sensitivity to alcohol. These results suggest that chronic sleep restriction induces a sustained impairment in adenosine-regulated sleep homeostasis and consequentially impacts the response to alcohol. PMID:24478367

  8. Erythromelalgia-like presentation of chronic acquired demyelinating polyneuropathy in a setting of past alcohol abuse.

    Science.gov (United States)

    Chuquilin, Miguel; Dhand, Upinder K

    2016-02-01

    Erythromelalgia may be primary or secondary to an underlying medical condition. Association with small fiber neuropathy and axonal large fiber peripheral neuropathy has been described. Erythromelalgia in the setting of acquired demyelinating neuropathy has not been reported. We report a 52-year-old woman with severe erythromelalgia, pain and burning, progressive weakness, hyporeflexia and distal pan-sensory deficits. Cerebrospinal fluid protein was 219 mg/dL. Nerve conduction study revealed extreme (ten-fold) prolongation of distal motor latencies, markedly slow motor nerve conduction, reduced terminal latency index, reduced distal compound muscle action potential (CMAP) amplitude, possible conduction blocks, and distal denervation. Treatment with intravenous immunoglobulin, prednisone and azathioprine resulted in marked clinical and electrophysiological improvement. Our patient fulfills the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP); however, the unique electrodiagnostic features and presentation with erythromelalgia may represent a CIDP variant or a novel dysimmune neuropathy, or may partly be related to neurotoxic effects of prior alcohol abuse. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Chronic Alcohol Intoxication and Cortical Ischemia: Study of Their Comorbidity and the Protective Effects of Minocycline

    Directory of Open Access Journals (Sweden)

    Enéas Andrade Fontes-Júnior

    2016-01-01

    Full Text Available Chronic alcohol intoxication (CAI increases both morbidity and mortality of stroke patients. Despite the high prevalence of CAI and ischemic stroke, studies addressing their comorbidity and/or protective alternatives remain scarce. Thus, the influence of CAI on both stroke outcome and minocycline treatment (recognized for its neuroprotective effect was investigated. Female Wistar rats (35 days old were treated with water or ethanol (6.5 g/kg/day, 22.5% w/v for 55 days. Then, focal ischemia was induced by endothelin-1 in the motor cortex. Two hours later, four doses of 50 mg/kg of minocycline every 12 hours followed by five doses of 25 mg/kg every 24 hours were administered. Behavioral performance (open field and rotarod tests and immunohistochemical (cellular density, neuronal death, and astrocytic activation and biochemical (lipid peroxidation and nitrite levels analyses were performed. CAI increased motor disruption, nitrite and lipid peroxidation levels, and neuronal loss caused by ischemia, whereas it reduced the astrogliosis. Minocycline was effective in preventing the motor and tissue damage caused by stroke. However, these effects were attenuated when CAI preceded stroke. Our data suggest that CAI beginning in adolescence contributes to a worse outcome in ischemic stroke survivors and reduces the benefits of minocycline, possibly requiring adjustments in therapy.

  10. Chronic Sleep Restriction Disrupts Sleep Homeostasis and Behavioral Sensitivity to Alcohol by Reducing the Extracellular Accumulation of Adenosine

    OpenAIRE

    Clasadonte, Jerome; Sally R McIver; Schmitt, Luke I.; Halassa, Michael M.; Haydon, Philip G

    2014-01-01

    Sleep impairments are comorbid with a variety of neurological and psychiatric disorders including depression, epilepsy, and alcohol abuse. Despite the prevalence of these disorders, the cellular mechanisms underlying the interaction between sleep disruption and behavior remain poorly understood. In this study, the impact of chronic sleep loss on sleep homeostasis was examined in C57BL/6J mice following 3 d of sleep restriction. The electroencephalographic power of slow-wave activity (SWA; 0.5...

  11. EFFECTS OF THE LITHIUM – CONTAINING SORBENT ON TERMS OF BEHAVIORAL REACTIONS UNDER CHRONIC ALCOHOL INTOXICATION MODEL

    OpenAIRE

    A. A. Kotlyarova; A. Yu. Letyagin; T. G. Tolstikova; T. V. Popova; L. N. Rachkovskaya

    2016-01-01

    Lithium preparations are widely used for stabilize mood in case of bipolar affective disorder. Currently neuroprotective and neuroregenerative effects of lithium are of interest as in case of acute brain injury, also in chronic neurodegenerative diseases such as dementia, alcoholism, Alzheimer disease, etc. [1–5]. In clinical practice use of lithium preparations is limited due to difficult adjustment of drug dosage, necessity of monitoring its concentration in blood, side effects development ...

  12. The occurrence and significance of fibronectin in livers from chronic alcoholics. An immunohistochemical study of early alcoholic liver injury

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Christoffersen, P

    1988-01-01

    localization. FN was closely correlating to the pattern of fibrosis but increased amounts of FN could also be seen in biopsies without fibrosis as visualized in Picro-Sirius stained sections. There was no topographical relationship to liver cells with fatty changes, Mallory bodies or to alcoholic hepatitis...

  13. Chronic alcohol consumption promotes hepatocarcinogenesis in mice through activation of beta-catenin.

    Science.gov (United States)

    Alcohol abuse is the most common cause of liver cancer in the United States, Although alcohol effects within the liver have been extensively studied, the mechanism by which alcohol causes liver cancer is complex. One mechanism involves speeding up tumor growth (promotion) by increasing the number of...

  14. Effects of Gabra2 Point Mutations on Alcohol Intake: Increased Binge-Like and Blunted Chronic Drinking by Mice.

    Science.gov (United States)

    Newman, Emily L; Gunner, Georgia; Huynh, Polly; Gachette, Darrel; Moss, Stephen J; Smart, Trevor G; Rudolph, Uwe; DeBold, Joseph F; Miczek, Klaus A

    2016-11-01

    Alcohol use disorders are associated with single-nucleotide polymorphisms in GABRA2, the gene encoding the GABAA receptor α2-subunit in humans. Deficient GABAergic functioning is linked to impulse control disorders, intermittent explosive disorder, and to drug abuse and dependence, yet it remains unclear whether α2-containing GABAA receptor sensitivity to endogenous ligands is involved in excessive alcohol drinking. Male wild-type (Wt) C57BL/6J and point-mutated mice rendered insensitive to GABAergic modulation by benzodiazepines (BZD; H101R), allopregnanolone (ALLO) or tetrahydrodeoxycorticosterone (THDOC; Q241M), or high concentrations of ethanol (EtOH) (S270H/L277A) at α2-containing GABAA receptors were assessed for their binge-like, moderate, or escalated chronic drinking using drinking in the dark, continuous access (CA) and intermittent access (IA) to alcohol protocols, respectively. Social approach by mutant and Wt mice in forced alcohol abstinence was compared to approach by EtOH-naïve controls. Social deficits in forced abstinence were treated with allopregnanolone (0, 3.0, 10.0 mg/kg, intraperitoneal [i.p.]) or midazolam (0, 0.56, 1.0 mg/kg, i.p.). Mice with BZD-insensitive α2-containing GABAA receptors (H101R) escalated their binge-like drinking. Mutants harboring the Q241M point substitution in Gabra2 showed blunted chronic intake in the CA and IA protocols. S270H/L277A mutants consumed excessive amounts of alcohol but, unlike wild-types, they did not show forced abstinence-induced social deficits. These findings suggest a role for: (i) H101 in species-typical binge-like drinking, (ii) Q241 in escalated chronic drinking, and (iii) S270 and/or L277 in the development of forced abstinence-associated social deficits. Clinical findings report reduced BZD-binding sites in the cortex of dependent patients; the present findings suggest a specific role for BZD-sensitive α2-containing receptors. In addition, amino acid residue 241 in Gabra2 is necessary

  15. [Differential diagnosis of ethanol poisoning, alcohol withdrawal, and chronic alcoholic intoxication from the changes in neurons and macroglyocytes in the cerebral cortex].

    Science.gov (United States)

    Droblenkov, A V

    2010-01-01

    The present paper reports results of a quantitative morphometric study of neuron and macroglyocyte populations in layers III and V of the brain somatosensory cortex in subjects with ethanol poisoning (EP), alcohol withdrawal (AW), and chronic alcoholic intoxication (CAI). The study was carried out during a more than 7-day period of abstinence in patients presenting with early manifestations of alcoholic illness. In subjects with ethanol poisoning, acute swelling of neurons in layer III was more pronounced than in layer V. Dynamic changes in the number of satellites near bodies of slightly affected neurons were recorded in layer III in patients with EP and AW as well as during the long-term break in intoxication. Layer V in EP, AW, and CAI exhibited phagocytosis of neurons, an elevated number of macroglyocytes and their enhanced proliferation along the course of blood vessels. The morphological changes of neurons and macroglyocytes under the above conditions can be categorized in terms of their degeneration rate from the beginning of the abstinence period into transient (disappearing within 7 days), persistent, and combined.

  16. Interactive Effects of Chronic Cigarette Smoking and Age on Brain Volumes in Controls and Alcohol Dependent Individuals in Early Abstinence

    Science.gov (United States)

    Durazzo, Timothy C.; Mon, Anderson; Pennington, David; Abé, Christoph; Gazdzinski, Stefan; Meyerhoff, Dieter J.

    2012-01-01

    Chronic alcohol use disorders (AUD) have been shown to interact with normal age-related volume loss to exacerbate brain atrophy with increasing age. However, chronic cigarette smoking, a highly comorbid condition in AUD, and its influence on age-related brain atrophy has not been evaluated. We performed 1.5T quantitative MRI in non-smoking controls (nsCON; n=54), smoking light drinking controls (sCON, n=34), and 1-week-abstinent, treatment-seeking non-smoking alcohol dependent individuals (nsALC, n=35) and smoking ALC (sALC, n=43), to evaluate the independent and interactive effects of alcohol dependence and chronic smoking on regional cortical and subcortical brain volumes, emphasizing the brain reward/executive oversight system (BREOS),. nsCON and sALC showed greater age-related volume losses than nsALC in the dorsal prefrontal cortex (DPFC), total cortical BREOS, superior parietal lobule and putamen. nsALC and sALC demonstrated smaller volumes than nsCON in most cortical ROIs. sCON had smaller volumes than nsCON in the DPFC, insula, inferior parietal lobule, temporal pole/parahippocampal region and all global cortical measures. nsALC and sALC had smaller volumes than sCON in the DPFC, superior temporal gyrus, inferior and superior parietal lobules, precuneus and all global cortical measures. Volume differences between nsALC and sALC were observed only in the putamen. Alcohol consumption measures were not related to volumes in any ROI for ALC; smoking severity measures were related to corpus callosum volume in sCON and sALC. The findings indicate that consideration of smoking status is necessary for a better understanding of the factors contributing to regional brain atrophy in AUD. PMID:22943795

  17. AN EXPERIMENTAL STUDY REGARDING THE BIOLOGICAL EFFECTS OF MINERAL WATER FROM SPRING 3 IN BĂILE TUŞNAD ON SOME ORGANS AFTER ETHYL ALCOHOL ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    Gabriela Dogaru

    2016-02-01

    Full Text Available Hepatobiliary and renal disorders are currently on the increase, being favored by increasing environmental pollution, alcohol consumption and synthesis drugs. Mineral water from spring 3 in Băile Tuşnad, with a total mineralization of 3351.0 mg/l, is recommended in chronic liver, gallbladder, pancreas diseases, kidney diseases and stones. This study aimed to assess potential changes in the liver, kidney, pancreas and stomach following ethyl alcohol administration in rats, as well as to monitor anatomopathological differences between animals that drank tap water and those that drank Tușnad mineral water, after cessation of ethyl alcohol administration. The study was carried out on 25 white Wistar rats over a period of 100 days. The animals were divided into 3 groups: group I, negative control group – 5 animals; group II, positive control group – 6 animals; group III, experimental group – 14 animals. The animals of group I received tap water (50-75 ml/day/animal throughout the experiment, and those of groups II and III were administered ethyl alcohol 12% (12-15 ml/day/animal during the first 70 days. During the last 30 days of the experiment, the animals of group II received tap water (50-75 ml/day/animal, and those of group III were administered Tuşnad mineral water (50-75 ml/day/animal. On experimental day 70, 5 animals were euthanized (2 of group I, 1 of group II and 2 of group III, and on day 100, the rest of 20 animals were euthanized. Fragments in the form of 4 mm thick slices from the liver, kidneys, pancreas and stomach of the euthanized animals were collected for histological investigations. The only changes detectable by optical microscopy were present in the liver. The rest of the studied organs did not show lesion aspects detectable by optical microscopy. The structural changes found in the liver were represented by mild to moderate fibrosis around the centrilobular venule in about 50% of the lobules. In the outer third of

  18. Immediate effects of alcohol marketing communications and media portrayals on consumption and cognition: a systematic review and meta-analysis of experimental studies

    Directory of Open Access Journals (Sweden)

    Kaidy Stautz

    2016-06-01

    Full Text Available Abstract Background Restricting marketing of alcoholic products is purported to be a cost-effective intervention to reduce alcohol consumption. The strength of evidence supporting this claim is contested. This systematic review aimed to assess immediate effects of exposure to alcohol marketing on alcoholic beverage consumption and related cognitions. Methods Electronic searches of nine databases, supplemented with reference list searches and forward citation tracking, were used to identify randomised, experimental studies assessing immediate effects of exposure to alcohol marketing communications on objective alcohol consumption (primary outcome, explicit or implicit alcohol-related cognitions, or selection without purchasing (secondary outcomes. Study limitations were assessed using the Cochrane Risk of Bias tool. Random and fixed effects meta-analyses were conducted to estimate effect sizes. Results Twenty four studies met the eligibility criteria. A meta-analysis integrating seven studies (758 participants, all students found that viewing alcohol advertisements increased immediate alcohol consumption relative to viewing non-alcohol advertisements (SMD = 0.20, 95 % CI = 0.05, 0.34. A meta-analysis integrating six studies (631 participants, all students did not find that viewing alcohol portrayals in television programmes or films increased consumption (SMD = 0.16, 95 % CI = −0.05, 0.37. Meta-analyses of secondary outcome data found that exposure to alcohol portrayals increased explicit alcohol-related cognitions, but did not find that exposure to alcohol advertisements influenced explicit or implicit alcohol-related cognitions. Confidence in results is diminished by underpowered analyses and unclear risk of bias. Conclusions Viewing alcohol advertisements (but not alcohol portrayals may increase immediate alcohol consumption by small amounts, equivalent to between 0.39 and 2.67 alcohol units for males and between 0.25 and 1

  19. Immediate effects of alcohol marketing communications and media portrayals on consumption and cognition: a systematic review and meta-analysis of experimental studies.

    Science.gov (United States)

    Stautz, Kaidy; Brown, Kyle G; King, Sarah E; Shemilt, Ian; Marteau, Theresa M

    2016-06-09

    Restricting marketing of alcoholic products is purported to be a cost-effective intervention to reduce alcohol consumption. The strength of evidence supporting this claim is contested. This systematic review aimed to assess immediate effects of exposure to alcohol marketing on alcoholic beverage consumption and related cognitions. Electronic searches of nine databases, supplemented with reference list searches and forward citation tracking, were used to identify randomised, experimental studies assessing immediate effects of exposure to alcohol marketing communications on objective alcohol consumption (primary outcome), explicit or implicit alcohol-related cognitions, or selection without purchasing (secondary outcomes). Study limitations were assessed using the Cochrane Risk of Bias tool. Random and fixed effects meta-analyses were conducted to estimate effect sizes. Twenty four studies met the eligibility criteria. A meta-analysis integrating seven studies (758 participants, all students) found that viewing alcohol advertisements increased immediate alcohol consumption relative to viewing non-alcohol advertisements (SMD = 0.20, 95 % CI = 0.05, 0.34). A meta-analysis integrating six studies (631 participants, all students) did not find that viewing alcohol portrayals in television programmes or films increased consumption (SMD = 0.16, 95 % CI = -0.05, 0.37). Meta-analyses of secondary outcome data found that exposure to alcohol portrayals increased explicit alcohol-related cognitions, but did not find that exposure to alcohol advertisements influenced explicit or implicit alcohol-related cognitions. Confidence in results is diminished by underpowered analyses and unclear risk of bias. Viewing alcohol advertisements (but not alcohol portrayals) may increase immediate alcohol consumption by small amounts, equivalent to between 0.39 and 2.67 alcohol units for males and between 0.25 and 1.69 units for females. The generalizability of this finding

  20. Correlation between spermatogenesis disorders and rat testes CYP2E1 mRNA contents under experimental alcoholism or type I diabetes.

    Science.gov (United States)

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Matvienko, Anatoliy V; Kovalenko, Valentina M

    2014-09-01

    The aim of the study was to investigate the correlation between spermatogenesis disorders and CYP2E1 mRNA contents in testes of rats with experimental alcoholism or type I diabetes. Two pathological states characterized by CYP2E1 induction were simulated on Wistar male rats: experimental alcoholism and type I diabetes. As controls for each state, equal number of animals (of the same age and weight) were used. Morphological evaluation of rat testes was carried out. The spermatogenic epithelium state was estimated by four points system. CYP2E1 mRNA expression was rated by method of reverse transcriptase polymerase chain reaction. Pearson correlation coefficients were used for describing relationships between variables. The presence of alcoholism and diabetes-mediated quantitative and qualitative changes in male rat spermatogenic epithelium in comparison with norm has been demonstrated. The increased levels of testes CYP2E1 have been fixed simultaneously. CYP2E1 mRNA content negatively strongly correlated with spermatogenic index value (r=-0.99; Palcoholism. The strong correlation between CYP2E1 mRNA content and number of spermatogonia (r=0.99; P<0.001) and "windows" occurrence (r=0.96; P<0.001) has been fixed in diabetic rats testes. Present investigation has demonstrated that the testicular failure following chronic ethanol consumption and diabetes type I in male rats accompanied CYP2E1 mRNA over-expression in testes. The correlation between the levels of CYP2E1 mRNA in testes and spermatogenesis disorders allow supposing the involvement of CYP2E1 into the non-specific pathogenetic mechanisms of male infertility under above-mentioned pathologies. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  1. Effects of Gabra2 point-mutations on alcohol intake: Increased binge-like and blunted chronic drinking by mice

    Science.gov (United States)

    Newman, Emily L.; Gunner, Georgia; Huynh, Polly; Gachette, Darrel; Moss, Stephen; Smart, Trevor; Rudolph, Uwe; DeBold, Joseph F.; Miczek, Klaus A.

    2016-01-01

    Background Alcohol use disorders are associated with single nucleotide polymorphisms in GABRA2, the gene encoding the GABAA receptor α2-subunit in humans. Deficient GABAergic functioning is linked to impulse control disorders, intermittent explosive disorder, and to drug abuse and dependence, yet it remains unclear if α2-containing GABAA receptor sensitivity to endogenous ligands is involved in excessive alcohol drinking. Methods Male wild-type C57BL/6J and point-mutated mice rendered insensitive to GABAergic modulation by benzodiazepines (H101R), allopregnanolone or THDOC (Q241M), or high concentrations of ethanol (S270H/L277A) at α2-containing GABAA receptors were assessed for their binge-like, moderate or escalated chronic drinking using drinking in the dark, continuous access and intermittent access to alcohol protocols, respectively. Social approach by mutant and wild-type mice in forced alcohol abstinence was compared to approach by EtOH-naïve controls. Social deficits in forced abstinence were treated with allopregnanolone (0, 3.0, 10.0 mg/kg, i.p.) or midazolam (0, 0.56, 1.0 mg/kg, i.p.). Results Mice with benzodiazepine-insensitive α2-containing GABAA receptors (H101R) escalated their binge-like drinking. Mutants harboring the Q241M point-substitution in Gabra2 showed blunted chronic intake in the continuous and intermittent access protocols. S270H/L277A mutants consumed excessive amounts of alcohol but, unlike wild-types, they did not show forced abstinence-induced social deficits. Conclusions These findings suggest a role for: 1.) H101 for species-typical binge-like drinking, 2.) Q241 for escalated chronic drinking, and 3.) S270 and/or L277 for the development of forced abstinence-associated social deficits. Clinical findings report reduced BZD-binding sites in the cortex of dependent patients; the present findings suggest a specific role for BZD-sensitive α2-containing receptors. In addition, amino acid residue 241 in Gabra2 is necessary for

  2. Chronic alcohol intake during adolescence, but not adulthood, promotes persistent deficits in risk-based decision making.

    Science.gov (United States)

    Schindler, Abigail G; Tsutsui, Kimberly T; Clark, Jeremy J

    2014-06-01

    Adolescent alcohol use is a major public health concern and is strongly correlated with the development of alcohol abuse problems in adulthood. Adolescence is characterized by maturation and remodeling of brain regions implicated in decision making and therefore may be uniquely vulnerable to environmental insults such as alcohol exposure. We have previously demonstrated that voluntary alcohol consumption in adolescence results in maladaptive risk-based decision making in adulthood. However, it is unclear whether this effect on risk-based decision making can be attributed to chronic alcohol use in general or to a selective effect of alcohol use during the adolescent period. Ethanol (EtOH) was presented to adolescent (postnatal day [PND] 30 to 49) and adult rats (PND 80 to 99) for 20 days, either 24 hours or 1 h/d, in a gel matrix consisting of distilled water, gelatin, polycose (10%), and EtOH (10%). The 24-hour time course of EtOH intake was measured and compared between adolescent and adult animals. Following 20 days of withdrawal from EtOH, we assessed risk-based decision making with a concurrent instrumental probability-discounting task. Blood EtOH concentrations (BECs) were taken from trunk blood and assessed using the Analox micro-stat GM7 in separate groups of animals at different time points. Unlike animals exposed to EtOH during adolescence, animals exposed to alcohol during adulthood did not display differences in risk preference compared to controls. Adolescent and adult rats displayed similar EtOH intake levels and patterns when given either 24- or 1-hour access per day. In addition, while both groups reached significant BEC levels, we failed to find a difference between adult and adolescent animals. Here, we show that adolescent, but not adult, EtOH intake leads to a persistent increase in risk preference which cannot be attributed to differences in intake levels or BECs attained. Our findings support previous work implicating adolescence as a time

  3. Antioxidant properties of jujube honey and its protective effects against chronic alcohol-induced liver damage in mice.

    Science.gov (United States)

    Cheng, Ni; Du, Bing; Wang, Yuan; Gao, Hui; Cao, Wei; Zheng, Jianbin; Feng, Fan

    2014-05-01

    The antioxidant potential of jujube honey, one of the most widely consumed honeys in China, has never been determined fully. In this study, jujube honey from six geographical origins in China was analyzed for individual phenolic acid, total phenolic content, and the antioxidant effect in chronic alcohol-related hepatic disease in mice. The results showed that jujube honey from Linxian of Shanxi province contained higher phenol levels, exhibited DPPH antioxidant activity, ferric ion reducing antioxidant power (FRAP) and protective effects against DNA damage. Treatment with jujube honey (Shanxi Linxian) for 12 weeks significantly inhibited serum lipoprotein oxidation, reduced the impact of alcoholism on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also inhibited the generation of 8-hydroxy-2-deoxyguanosine (8-OHdG), lowered the levels of malondialdehyde (MDA) and increased the activity of hepatic glutathione peroxidase (GSH-Px). The study indicates that jujube honey exerts potent antioxidant activity and significant protection in hepatic disorders associated with chronic alcoholism. The protective effect is attributed to its antioxidant mechanisms and inhibition of oxidative degradation of lipids.

  4. Acute High-Dose and Chronic Lifetime Exposure to Alcohol Consumption and Differentiated Thyroid Cancer: T-CALOS Korea.

    Directory of Open Access Journals (Sweden)

    Yunji Hwang

    Full Text Available This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC.The Thyroid Cancer Longitudinal Study (T-CALOS included 2,258 DTC patients (449 men and 1,809 women and 22,580 healthy participants (4,490 men and 18,090 women who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs and 95% confidence intervals (95%CI were estimated using conditional regression models.While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion was associated with increased risks in men (OR = 2.22, 95%CI = 1.27-3.87 and women (OR = 3.61, 95%CI = 1.52-8.58 compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31-40 years: OR = 1.58, 95%CI = 1.10-2.28; 41+ years: OR = 3.46, 95%CI = 2.06-5.80 and women (31-40 years: OR = 2.18, 95%CI = 1.62-2.92; 41+ years: OR = 2.71, 95%CI = 1.36-5.05 compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage.The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC.

  5. Effects of stress on alcohol drinking: a review of animal studies.

    Science.gov (United States)

    Becker, Howard C; Lopez, Marcelo F; Doremus-Fitzwater, Tamara L

    2011-11-01

    While stress is often proposed to play a significant role in influencing alcohol consumption, the relationship between stress and alcohol is complex and poorly understood. Over several decades, stress effects on alcohol drinking have been studied using a variety of animal models and experimental procedures, yet this large body of literature has generally produced equivocal results. This paper reviews results from animal studies in which alcohol consumption is evaluated under conditions of acute/sub-chronic stress exposure or models of chronic stress exposure. Evidence also is presented indicating that chronic intermittent alcohol exposure serves as a stressor that consequently influences drinking. The effects of various acute/sub-chronic stress procedures on alcohol consumption have generally been mixed, but most study outcomes suggest either no effect or decreased alcohol consumption. In contrast, most studies indicate that chronic stress, especially when administered early in development, results in elevated drinking later in adulthood. Chronic alcohol exposure constitutes a potent stressor itself, and models of chronic intermittent alcohol exposure reliably produce escalation of voluntary alcohol consumption. A complex and dynamic interplay among a wide array of genetic, biological, and environmental factors govern stress responses, regulation of alcohol drinking, and the circumstances in which stress modulates alcohol consumption. Suggestions for future directions and new approaches are presented that may aid in developing more sensitive and valid animal models that not only better mimic the clinical situation, but also provide greater understanding of mechanisms that underlie the complexity of stress effects on alcohol drinking.

  6. Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espírito Santo.

    Science.gov (United States)

    Gonçalves, Patricia Lofego; Zago-Gomes, Maria da Penha; Marques, Carla Couzi; Mendonça, Ana Tereza; Gonçalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

    2013-01-01

    To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2 ± 12.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1 %), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1 %), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (pAlcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis.

  7. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

    Science.gov (United States)

    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Frontal lobe dysfunctions in Korsakoff's syndrome and chronic alcoholism: Continuity or discontinuity?

    NARCIS (Netherlands)

    Brokate, B.; Hildebrandt, H.; Eling, P.A.T.M.; Fichtner, H.; Runge, K.; Timm, C.

    2003-01-01

    The effect of long-term heavy alcohol consumption on brain functions is still under debate. The authors investigated a sample of 17 Korsakoff amnesics, 23 alcoholics without Korsakoff's syndrome, and 21 controls with peripheral nerve diseases, matched for intelligence and education. Executive

  9. Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Abdallah, K; Chitnis, T

    2000-01-01

    The mechanisms of chronic disease and recovery from relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, are unknown. Deletion of myelin-specific lymphocytes by apoptosis may play a role in termination of the inflammatory response. One pathway....... We found that mice transgenic for Bcl-x(L) have an earlier onset and a more chronic form of EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 compared with wild-type littermate mice. This was not due to an expanded autoreactive cell repertoire. Primed peripheral lymphocytes from...... that the passive cell death pathway is important in the pathogenesis of chronic EAE. These findings have implications for understanding the pathogenesis of multiple sclerosis and other autoimmune diseases....

  10. Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia

    Science.gov (United States)

    Olbryt, Magdalena; Habryka, Anna; Student, Sebastian; Jarząb, Michał; Tyszkiewicz, Tomasz; Lisowska, Katarzyna Marta

    2014-01-01

    Hypoxia is one of the most important features of the tumor microenvironment, exerting an adverse effect on tumor aggressiveness and patient prognosis. Two types of hypoxia may occur within the tumor mass, chronic (prolonged) and cycling (transient, intermittent) hypoxia. Cycling hypoxia has been shown to induce aggressive tumor cell phenotype and radioresistance more significantly than chronic hypoxia, though little is known about the molecular mechanisms underlying this phenomenon. The aim of this study was to delineate the molecular response to both types of hypoxia induced experimentally in tumor cells, with a focus on cycling hypoxia. We analyzed in vitro gene expression profile in three human cancer cell lines (melanoma, ovarian cancer, and prostate cancer) exposed to experimental chronic or transient hypoxia conditions. As expected, the cell-type specific variability in response to hypoxia was significant. However, the expression of 240 probe sets was altered in all 3 cell lines. We found that gene expression profiles induced by both types of hypoxia were qualitatively similar and strongly depend on the cell type. Cycling hypoxia altered the expression of fewer genes than chronic hypoxia (6,132 vs. 8,635 probe sets, FDR adjusted pcycling hypoxia than by prolonged hypoxia, such as IL8, PLAU, and epidermal growth factor (EGF) pathway-related genes (AREG, HBEGF, and EPHA2). These transcripts were, in most cases, validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our results indicate that experimental cycling hypoxia exerts similar, although less intense effects, on the examined cancer cell lines than its chronic counterpart. Nonetheless, we identified genes and molecular pathways that seem to be preferentially regulated by cyclic hypoxia. PMID:25122487

  11. How cognitive assessment through clinical neurophysiology may help optimize chronic alcoholism treatment.

    Science.gov (United States)

    Campanella, S; Petit, G; Verbanck, P; Kornreich, C; Noel, X

    2011-07-01

    Alcohol dependence constitutes a serious worldwide public health problem. The last few decades have seen many pharmacological studies devoted to the improvement of alcoholism treatment. Although psychosocial treatments (e.g. individual or group therapy) have historically been the mainstay of alcoholism treatment, a successful approach for alcohol dependence consists in associating pharmacologic medications with therapy, as 40-70% of patients following only psychosocial therapy typically resume alcohol use within a year of post-detoxification treatment. Nowadays, two main pharmacological options, naltrexone and acomprosate, both approved by the US Food and Drug Administration, are available and seemingly improve on the results yielded by standard techniques employed in the management of alcoholism. However, insufficient data exist to confirm the superiority of one drug over the other, and research is ongoing to determine what type of alcohol-dependent individual benefits the most from using either medication. Available data on the application of both drugs clearly suggest different practical applications. Thus, a fundamental question remains as to how we can identify which alcoholic patients are likely to benefit from the use of naltrexone, acamprosate or both, and which are not. The aim of the present manuscript is to suggest the use of cognitive event-related potentials as an interesting way to identify subgroups of alcoholic patients displaying specific clinical symptoms and cognitive disturbances. We propose that this may help clinicians improve their treatment of alcoholic patients by focusing therapy on individual cognitive disturbances, and by adapting the pharmaceutical approach to the specific needs of the patient. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  12. The effect of chronic alcohol administration on bone mineral content and bone strength in male rats.

    Science.gov (United States)

    Broulík, P D; Vondrová, J; Růzicka, P; Sedlácek, R; Zíma, T

    2010-01-01

    Alcohol use has been identified as a risk factor for the development of osteoporosis. Eight male Wistar rats at two months of age were alcoho-fed (7.6 g 95 % ethanol/kg b.w. per day) to evaluate the effects of long-term administration (three months) of alcohol in drinking water. We have used a dose which is considered to be comparable to a dose of 1 liter of wine or 2.5 liters of 12(°) beer used in male adults daily. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. The bones from alcohol-fed rats were characterized by a reduction in bone density as well as in ash, calcium and phosphate content. In alcohol-fed rats the reduction in bone mineral density (10 %) was reflected by about 12 % reduction of mechanical strength of femur (158+/-5.5 vs. 178+/-3.2 N/mm(2)). Alcohol significantly altered femoral cortical thickness. In our experiment alcohol itself did not exert any antiandrogenic effect and it did not produce changes in the weight of seminal vesicles. Liver function test (GGT, ALP, AST) did not differ between alcohol-fed rats and control rats. Alcohol-induced bone loss is associated with increased bone resorption and decreased bone formation. These results document the efficacy of alcohol at the dose of 7.6 g 95 % ethanol/kg b.w. to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of alcohol as a risk factor for osteoporosis.

  13. Chronic intermittent hypoxia and obstructive sleep apnea: an experimental and clinical approach

    Directory of Open Access Journals (Sweden)

    Sforza E

    2016-04-01

    Full Text Available Emilia Sforza, Fréderic Roche Service de Physiologie Clinique et de l'Exercice, Pole NOL, CHU, EA SNA-EPIS 4607, Faculté de Médecine J. Lisfranc, UJM Saint-Etienne, Université de Lyon, Saint-Etienne, France Abstract: Obstructive sleep apnea (OSA is a prevalent sleep disorder considered as an independent risk factor for cardiovascular consequences, such as systemic arterial hypertension, ischemic heart disease, cardiac arrhythmias, metabolic disorders, and cognitive dysfunction. The pathogenesis of OSA-related consequence is assumed to be chronic intermittent hypoxia (IH inducing alterations at the molecular level, oxidative stress, persistent systemic inflammation, oxygen sensor activation, and increase of sympathetic activity. Overall, these mechanisms have an effect on vessel permeability and are considered to be important factors for explaining vascular, metabolic, and cognitive OSA-related consequences. The present review attempts to examine together the research paradigms and clinical studies on the effect of acute and chronic IH and the potential link with OSA. We firstly describe the literature data on the mechanisms activated by acute and chronic IH at the experimental level, which are very helpful and beneficial to explaining OSA consequences. Then, we describe in detail the effect of IH in patients with OSA that we can consider "the human model" of chronic IH. In this way, we can better understand the specific pathophysiological mechanisms proposed to explain the consequences of IH in OSA. Keywords: hypoxia, intermittent hypoxia, experimental studies, obstructive sleep apnea

  14. Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome.

    Science.gov (United States)

    Roman, Kenny; Done, Joseph D; Schaeffer, Anthony J; Murphy, Stephen F; Thumbikat, Praveen

    2014-07-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine EAP. Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia led to extracellular signal-regulated kinase (ERK)1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. [Effects of Acupuncture on Neurofunction and Neuropsychological Factors of Chronic Alcoholic Peripheral Neuropathy Patients].

    Science.gov (United States)

    Mei, Jun-hua; Wang, Jun-il; Luo, Li-jun; Chen, Guo-hua; Zhang, Zhong-wen; Pan, Xiao-feng; Wei, Dan; Shao, Wei

    2015-12-01

    To observe the effects of acupuncture on neurofunction and neuropsychological factors of chronic alcoholic peripheral neuropathy (CAPN) patients. Totally 120 CAPN patients were assigned to the common treatment group, acupuncture group A, and acupuncture group B according to random digit table, 40 in each group. All patients recieved conventional drug therapy. Besides, patients in the acupuncture group A were additionally needled at Pishu (BL20), Weishu (BL21), Xuehai (SP10), Yinlingquan (SP9), Zusanli (ST36), Yanglingquan (GB34), Jiexi (ST41), Xuanzhong (GB39), Xiangu (ST43),Taixi (KI3), Quchi (LI11), Waiguan (SJ5), Hegu (LI4), and so on. On these bases patients in the acupuncture group B were needled at Sishencong (EX-HN1), Yintang (EX-HN3), Neiguan (PC6), Taichong (LR3), Sanyinjiao (SP6), and Taiyang (EX-HN5). Acupuncture was performed once a day, 14 times as a course; and then once on every other day, 14 times in total for 4 weeks. All treatment lasted for 8 successive weeks. Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Neurological Severity Score (NSS), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA) were assessed, motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) were detected before and after treatment. After 8 weeks of treatment the scores of NIS-LL and NSS significantly decreased in the 3 groups, with statistical difference as compared with before treatment (P acupuncture groups A and B than in the common treatment group (P acupuncture group B (P acupuncture treatment group A and B after 8-week treatment (P acupuncture treatment groups A and B after treatment (P acupuncture treatment group A than in acupuncture treatment group B (P acupuncture groups A and B, with statistical difference as compared with before treatment (P acupuncture treatment group B than in acupuncture treatment group A (P Acupuncture therapy could effectively improve the neurofunction of CAPN patients, and improve

  16. The effects of changes in glutathione levels through exogenous agents on intracellular cysteine content and protein adduct formation in chronic alcohol-treated VL17A cells.

    Science.gov (United States)

    Kumar, S Mathan; Haridoss, Madhumitha; Swaminathan, Kavitha; Gopal, Ramesh Kumar; Clemens, Dahn; Dey, Aparajita

    2017-02-01

    Alcohol-mediated liver injury is associated with changes in the level of the major cellular antioxidant glutathione (GSH). It is interesting to investigate if the changes in intracellular GSH level through exogenous agents affect the intracellular cysteine content and the protein adduct formation indicative of oxidative insult in chronic alcohol treated liver cells. In VL-17A cells treated with 2 mM N-acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) plus 100 mM ethanol, an increase in cysteine concentration which was accompanied by decreases in hydroxynonenal (HNE) and glutathionylated protein adducts were observed. Pretreatment of 100 mM ethanol treated VL-17A cells with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) had opposite effects. Thus, altered GSH level through exogenous agents may either potentiate or ameliorate chronic alcohol-mediated protein adduct formation and change the cysteine level in chronic alcohol treated VL-17A cells. The gene expression of non-treated and ethanol-treated hepatocytes in 2 microarray datasets was also compared to locate differentially expressed genes involved in cysteine metabolism. The study demonstrates that increased protein adducts formation and changes in cysteine concentration occur under chronic alcohol condition in liver cells which may increase alcohol-mediated oxidative injury.

  17. Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss.

    Science.gov (United States)

    Clugston, Robin D; Huang, Li-Shin; Blaner, William S

    2015-09-01

    The alcohol-induced depletion of hepatic retinoid stores correlates with the progression of liver injury; however, the mechanisms underlying alcohol's effects have not been fully elucidated. Our goal was to gain a mechanistic understanding of alcohol-induced hepatic retinoid depletion. Wild-type and mutant mice were continuously fed alcohol through Lieber-DeCarli liquid diets, with matched control animals pair fed an isocaloric alcohol-free diet to ensure equal nutrient and calorie intake between groups. A systematic analysis of tissue retinol and retinyl ester levels was performed with HPLC, complemented by gene and protein expression analyses. Our results delineated 2 phases of alcohol-induced depletion of hepatic retinoid. Initially, ∼15% of hepatic retinoid content was mobilized from the liver, causing extrahepatic tissue retinoid levels to increase. Subsequently, there was a precipitous drop in hepatic retinoid content (>60%), without further retinoid accumulation in the periphery. Follow-up studies in mutant mice revealed roles for RBP, CRBP1, and CD36 in retinoid mobilization and extrahepatic retinoid uptake, as well as a role for CYP2E1 in the catabolism of hepatic retinoid. In summary, alcohol has a biphasic effect on hepatic retinoid stores, characterized by an initial phase of rapid mobilization to extrahepatic tissues followed by extensive catabolism within the liver. © FASEB.

  18. Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

    Science.gov (United States)

    Fan, Fan; Cao, Quan; Wang, Cong; Ma, Xin; Shen, Cheng; Liu, Xiang-wei; Bu, Li-ping; Zou, Yun-zeng; Hu, Kai; Sun, Ai-jun; Ge, Jun-bo

    2014-08-01

    To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice. Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles. Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles. Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

  19. Brain docosahexaenoic acid [DHA] incorporation and blood flow are increased in chronic alcoholics: a positron emission tomography study corrected for cerebral atrophy.

    Directory of Open Access Journals (Sweden)

    John C Umhau

    Full Text Available Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22∶6n-3, particularly if liver disease is present. In animal models, excessive alcohol consumption is reported to reduce brain DHA concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism also is abnormal in chronic alcoholics.We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, with 22 non-smoking healthy controls. Using published neuroimaging methods with positron emission tomography (PET, we measured regional coefficients (K* and rates (J(in of DHA incorporation from plasma into the brain of each group using [1-(11C]DHA, and regional cerebral blood flow (rCBF using [(15O]water. Data were partial volume error corrected for brain atrophy. Plasma unesterified DHA concentration also was quantified.Mean K* for DHA was significantly and widely elevated by 10-20%, and rCBF was elevated by 7%-34%, in alcoholics compared with controls. Unesterified plasma DHA did not differ significantly between groups nor did whole brain J(in, the product of K* and unesterified plasma DHA concentration.Significantly higher values of K* for DHA in alcoholics indicate increased brain avidity for DHA, thus a brain DHA metabolic deficit vis-à-vis plasma DHA availability. Higher rCBF in alcoholics suggests increased energy consumption. These changes may reflect a hypermetabolic state related to early alcohol withdrawal, or a general brain metabolic change in chronic alcoholics.

  20. Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis.

    Science.gov (United States)

    Mohan, Surapaneni Krishna; Veeraraghavan, Vishnu Priya; Jainu, Mallika

    2015-08-01

    Non-alcoholic steatohepatitis (NASH), is an important component of Non-alcoholic fatty liver disease (NAFLD) spectrum, which progresses to the end stage liver disease, if not diagnosed and treated properly. The disproportionate production of pro- and anti-inflammatory adipokines secreted from fat contributes to the pathogenesis of NASH. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix (ECM) component levels were studied in experimentally induced NASH. The experimental protocol consists of using 48 male Wister rats, which were divided into 8 groups. The levels of hyaluronic acid, leptin and adiponectin were monitored in experimental NASH. The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showed significant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid.

  1. Does alcohol consumption really affect asymmetry perception? A three-armed placebo-controlled experimental study.

    Science.gov (United States)

    Halsey, Lewis G; Huber, Joerg W; Hardwick, Jennifer C

    2012-07-01

      A possible explanation for increased levels of attractiveness of faces when under the influence of alcohol is the reduced ability to perceive bilateral asymmetry. This study tested the degree of preference by alcohol-dosed and non-alcohol-dosed participants for symmetrical faces and their ability to detect facial symmetry, while controlling for other explanations.   Volunteers were recruited to a random allocation experiment with three conditions: alcoholic drink (alcohol dosed), non-alcoholic drink (placebo) and diluted orange cordial (control). Data on concentration, personality and demographics were collected. Dependent variables were symmetry preference and detection.   Laboratory, University of Roehampton.   A total of 101 participants, mainly students (41 alcohol-dosed, 40 placebo, 20 control).   Participants provided verbal responses to images of faces which were presented on a computer screen for 5 seconds each; the first task required a preference judgement and the second task consisted of a forced-choice response of whether or not a face was symmetrical. Levels of concentration, weight and level of alcohol dose were measured, and demographics plus additional psychological and health information were collected using a computer-based questionnaire.   In contrast to a previous investigation, there was no difference in symmetry preference between conditions (P = 0.846). In agreement with previous findings, participants who had not drunk alcohol were better at detecting whether a face was symmetrical or asymmetrical (P = 0.043). Measures of concentration did not differ between conditions (P = 0.214-0.438). Gender did not affect ability to detect symmetry in placebo or alcohol-dosed participants (P = 0.984, 0.499); however, alcohol-dosed females were shown to demonstrate greater symmetry preference than alcohol-dosed males (P = 0.004).   People who are alcohol-dosed are subtly less able to perceive vertical, bilateral

  2. Impact of experimentally induced positive and anxious mood on alcohol expectancy strength in internally motivated drinkers.

    Science.gov (United States)

    Grant, Valerie V; Stewart, Sherry H

    2007-01-01

    The effects of musically-induced positive and anxious mood on explicit alcohol-related cognitions (alcohol expectancy strength) in 47 undergraduate students who consume alcohol either to enhance positive mood states (for enhancement motives) or to cope with anxiety (for anxiety-related coping motives) were investigated. Pre- and post-mood induction, participants completed the emotional reward and emotional relief subscales of the Alcohol Craving Questionnaire - Now. The hypothesis that anxiety-related coping motivated drinkers in the anxious mood condition (but not those in the positive mood condition) would exhibit increases in strength of explicit emotional relief alcohol expectancies after the mood induction was supported. An additional, unanticipated finding was that enhancement-motivated drinkers in the anxious condition also showed significant increases in strength of explicit emotional relief (but not emotional reward) alcohol expectancies. The hypothesis that enhancement-motivated (but not anxiety-related coping motivated) participants would exhibit increases in explicit emotional reward expectancies following exposure to the positive mood induction procedure was not supported. Taken together with past research findings, the current results highlight the importance of distinguishing between subtypes of negative affect (i.e., anxious and depressed affect) in exploring the affective antecedents of explicit alcohol outcome expectancies.

  3. Acute and Chronic Effects of Alcohol Use on Organizational Processes in Memory

    Science.gov (United States)

    Rosen, Linda J.; Lee, Catherine L.

    1976-01-01

    Subjects selected on the basis of their drinking histories (alcoholics, heavy drinkers, and social drinkers, N=24) were tested on a series of tasks in order to assess organizational processes in memory. (Editor)

  4. Chronic moderate alcohol consumption induces iNOS expression in the penis: An immunohistochemical study

    OpenAIRE

    GONCA, Süheyla; YAZIR, Yusufhan; GÖÇMEZ, Semil Selcan; DALÇIK, Ekim Nur; Utkan, Tijen; DALÇIK, Hakkı

    2014-01-01

    To investigate the effect of moderate alcohol consumption on metabolic alterations, inducible nitric oxide synthase (iNOS), immunohistochemical distribution, and morphological damage to penile erectile tissue in rats. Materials and methods: Male Wistar albino rats were divided into 2 groups. Group 1 rats (control group, n = 8) received tap water ad libitum, and group 2 rats (n = 8) were fed with 20% ethanol. Increasing levels of alcohol were given to the rats over 12 weeks. Immunohistochemi...

  5. Zinc-deficiency acrodermatitis in a patient with chronic alcoholism and gastric bypass: a case report

    Directory of Open Access Journals (Sweden)

    Dariush Shahsavari

    2014-07-01

    Full Text Available Acquired adult-onset zinc deficiency is occasionally reported in patients with malnutrition states, such as alcoholism, or malabsorptive states, such as post-bariatric surgery. The defining symptoms of hypozincemia include a classic triad of necrolytic dermatitis, diffuse alopecia, and diarrhea. We report a case of zinc deficiency in a 39-year-old man with history of gastric bypass surgery and alcoholism. For this patient, severe hypozincemia confirmed acrodermatitis, and zinc supplementation was met with gradual improvement.

  6. Applicability of the Rivermead Behavioural Memory Test – Third Edition (RBMT-3 in Korsakoff's syndrome and chronic alcoholics

    Directory of Open Access Journals (Sweden)

    Wester AJ

    2013-06-01

    Full Text Available Arie J Wester,1 Judith C van Herten,2 Jos IM Egger,2–4 Roy PC Kessels1,2,5 1Korsakoff Clinic, Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands; 2Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands; 3Centre of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands; 4Behavioral Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands; 5Department of Medical Psychology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Purpose: To examine the applicability of the newly developed Rivermead Behavioural Memory Test – Third Edition (RBMT-3 as an ecologically-valid memory test in patients with alcohol-related cognitive disorders. Patients and methods: An authorized Dutch translation of the RBMT-3 was developed, equivalent to the UK version, and administered to a total of 151 participants – 49 patients with amnesia due to alcoholic Korsakoff's syndrome, 49 patients with cognitive impairment and a history of chronic alcoholism, not fulfilling the Korsakoff criteria, and 53 healthy controls. Between-group comparisons were made at subtest level, and the test's diagnostic accuracy was determined. Results: Korsakoff patients performed worse than controls on all RBMT-3 subtests (all P-values < 0.0005. The alcoholism group performed worse than controls on most (all P-values < 0.02, but not all RBMT-3 subtests. Largest effects were found between the Korsakoff patients and the controls after delayed testing. The RBMT-3 had good sensitivity and adequate specificity. Conclusion: The RBMT-3 is a valid test battery to demonstrate everyday memory deficits in Korsakoff patients and non-Korsakoff patients with alcohol abuse disorder. Korsakoff patients showed an impaired performance on subtests relying on orientation, contextual memory and delayed testing. Our findings provide valuable information for treatment

  7. Chronic binge alcohol consumption during pregnancy alters rat maternal uterine artery pressure response.

    Science.gov (United States)

    Naik, Vishal D; Lunde-Young, Emilie R; Davis-Anderson, Katie L; Orzabal, Marcus; Ivanov, Ivan; Ramadoss, Jayanth

    2016-11-01

    We aimed to investigate pressure-dependent maternal uterine artery responses and vessel remodeling following gestational binge alcohol exposure. Two groups of pregnant rats were used: the alcohol group (28.5% wt/v, 6.0 g/kg, once-daily orogastric gavage in a binge paradigm between gestational day (GD) 5-19) and pair-fed controls (isocalorically matched). On GD20, excised, pressurized primary uterine arteries were studied following equilibration (60 mm Hg) using dual chamber arteriograph. The uterine artery diameter stabilized at 20 mm Hg, showed passive distension at 40 mm Hg, and redeveloped tone at 60 mm Hg. An alcohol effect (P = 0.0025) was observed on the percent constriction of vessel diameter with greater pressure-dependent myogenic constriction. Similar alcohol effect was noted with lumen diameter response (P = 0.0020). The percent change in media:lumen ratio was higher in the alcohol group (P alcohol affects pressure-induced uterine artery reactivity, inward-hypotrophic remodeling, and adaptations critical for nutrient delivery to the fetus. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of nifurtimox and benznidazole.

    Science.gov (United States)

    de Mecca, M M; Bartel, L C; Castro, J A

    2013-12-01

    Nifurtimox (Nfx) and benznidazole (Bz) have serious toxic side effects. Manufacturers warn about significant adverse effects when simultaneous alcohol consumption is being made, but its mechanism is not known. The levels and toxicity of these drugs are linked to their liver microsomal nitroreduction to reactive metabolites. In this study, we analyzed whether alcohol drinking enhanced those nitroreductive processes. Male and female Sprague-Dawley rats, 5-6 weeks old (125-150 g body weight) were used. They were fed ad libitum for 28 days with Lieber and De Carli control or alcohol regular liquid diets. The rats were separated into two dietary groups: ethanol and control group. Both were pair fed with the respective diet. Their liver microsomes were isolated and the nicotinamide adenine dinucleotide phosphate-dependent nitroreduction of Nfx and Bz were determined. Alcohol drinking significantly induced microsomal nitroreduction of these drugs in male rats (11% for Nfx and 41% for Bz) but not in females. The activity observed in the alcohol-induced male rats was 100% inhibited by diphenyleneiodonium and attributable to P450 reductase. Inductive effects of alcohol drinking on nitroreductive activation of both drugs might be only partially involved in the harmful interactions described.

  9. Observational Research on Alcohol Use and Chronic Disease Outcome: New Approaches to Counter Biases

    Directory of Open Access Journals (Sweden)

    Wenbin Liang

    2013-01-01

    Full Text Available Background. The frequently reported protective effects of moderate alcohol consumption in observational studies may be due to unadjusted bias. Aim. To examine two new approaches that account for unknown confounding factors and allow the application of intention-to-treat analysis. Method. This study used data from the 2008, 2009, and 2010 National Health Interview Surveys conducted in the United States. Unknown confounding effects were estimated through the association between parental alcohol use and health outcomes for children, because the presence of hypothetical physiological effects of alcohol can be ruled out for this association. In order to apply intention-to-treat analysis, previous alcohol use of former drinkers was obtained by using multiple imputations. Estimates with new adjustment approaches were compared with the traditional approach. Results. The traditional analytical approach; appears to be consistent with findings from previous observational studies; when two further adjustment approaches were used, the “protective” effects of moderate drinking almost disappeared. Conclusion. Use of a proxy outcome to estimate and control residual confounding effects of alcohol use and application of the intention-to-treat principle could provide a more realistic estimation of the true effects of alcohol use on health outcomes in observational epidemiological studies.

  10. Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

    Science.gov (United States)

    Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-02

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. [Management of chronic kidney disease guided by the theory of Traditional Chinese Medicine: an experimental study].

    Science.gov (United States)

    Wen, Ji; Xie, Xi-Sheng; Zhang, Ming-Hua; Mao, Nan; Zhang, Cheng-Long; Xie, Lin-Shen; Cheng, Yuan; Zhang, Zi-Yuan; Fan, Jun-Ming

    2014-01-01

    To determine the impact of Traditional Chinese Medicine on patients with chronic kidney disease (CKD). A total of 225 CKD patients in an outpatient department were recruited for this study, among whom 170 received regular Western and Chinese medicine treatments (control group) and 55 received treatments guided by the theory of Traditional Chinese Medicine (experimental group). The effectiveness of the treatments was determined through a pre-post comparison. Significant pre-intervention differences in age (P experimental group had a greater level of decrease in blood urea nitrogen (P experimental group compared with the control (P Medicine can improve renal function through influencing glomerular filtration rate. The effect is more prominent than the regular treatment regime.

  12. Experimental Study on the Distillation Capacity of Alcohol-Gasoline Blends

    Science.gov (United States)

    Stan, C.; Andreescu, C.; Dobre, A.; Iozsa, D.

    2017-10-01

    The paper objective is to highlight the consequences of adding different alcohols in gasoline on the distillation characteristics of these blends. Changes of the distillation parameters (ti, t10, t50, t90, tf, E70, E100, E150) have been evaluated and, also, the evolution trends of the distillation curves for different alcohol added in mixture with the gasoline have been estimated. Several types of gasoline sold on the market and methanol, ethanol, i-propanol and butanol were used during the experiments and the corresponding distillation curves have been analyzed. The alcohol fraction in mixtures varied between 5 and 20%. Double blends with alcohol added in gasoline and triple blends with two alcohols added in gasoline were used. The comparison of the distillation curves of the mixtures was done with respect to that of pure gasoline. It was specified how the values of the distillation parameters, E70, E100 and E150, were set within the limits of EN 228. The distillation was made on 100 ml of fuel and the measurements were made on each 10 ml of fuel transformed into vapor state and then condensed. The influence of the alcohols present in these mixtures was manifested by the changes in the shape of the distillation curve. The butanol influence on the distillation temperatures was found lower than that of ethanol, because the physicochemical properties of the butanol are closer to those of gasoline. The molecules of alcohols actively interact with the fractions of gasolines, their combination leading to a conjugate effect and to a modifying the distillation parameters values. The variation of these parameters depends on the alcohol fraction in the mixture.

  13. Chronic disease and recent addiction treatment utilization among alcohol and drug dependent adults

    OpenAIRE

    Samet Jeffrey; Allensworth-Davies Donald; Cheng Debbie M; Larson Mary Jo; Reif Sharon; Saitz Richard

    2011-01-01

    Abstract Background Chronic medical diseases require regular and longitudinal care and self-management for effective treatment. When chronic diseases include substance use disorders, care and treatment of both the medical and addiction disorders may affect access to care and the ability to focus on both conditions. The objective of this paper is to evaluate the association between the presence of chronic medical disease and recent addiction treatment utilization among adults with substance de...

  14. Effect of Non-Alcoholic Compounds of Alcoholic Drinks on the Pancreas

    Science.gov (United States)

    Feick, Peter; Gerloff, Andreas; Singer, Manfred V.

    2007-01-01

    Over the past 30 years the role of alcohol (ethanol) in the development of acute and chronic pancreatitis has been intensively investigated. However, ethanol is generally consumed in form of alcoholic beverages which contain numerous non-alcoholic compounds. At least on gastric acid secretion it has been convincingly demonstrated that alcohol and alcoholic beverages have markedly different effects. In the present article, we provide an overview about the effect of different non-alcoholic constituents of alcoholic beverages on the pancreas and their possible interaction with molecular mechanisms leading to ‘alcoholic’ pancreatitis. The present data indicate that pancreatic enzyme secretion in humans is stimulated by non-alcoholic constituents of beer which are generated by alcoholic fermentation of glucose. In addition, it has been shown that natural phenolic compounds (e.g. quercetin, resveratrol) of alcoholic beverages exert different effects on the pancreasin vitro, such as inhibition of pancreatic enzyme output, of pancreatic stellate cell activation and of pancreatic cancer growth as well as protective effects against oxidative stress and on experimental induced acute pancreatitis in rats. However, it should be pointed out that alcoholic beverages contain much more non-alcoholic ingredients. Since the effects of these are still unknown, caution is required in attempting to define alcoholic etiology of pancreatitis without considering the effect of non-alcoholic compounds of alcoholic beverages. PMID:17592224

  15. Alcoholic hallucinosis

    Directory of Open Access Journals (Sweden)

    Pookala S Bhat

    2012-01-01

    Full Text Available Alcoholic hallucinosis is a rare complication of chronic alcohol abuse characterized by predominantly auditory hallucinations that occur either during or after a period of heavy alcohol consumption. Bleuler (1916 termed the condition as alcohol hallucinosis and differentiated it from Delirium Tremens. Usually it presents with acoustic verbal hallucinations, delusions and mood disturbances arising in clear consciousness and sometimes may progress to a chronic form mimicking schizophrenia. One such case with multimodal hallucinations in a Defence Service Corps soldier is presented here.

  16. Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

    Directory of Open Access Journals (Sweden)

    Glaucia Vilar-Pereira

    2015-12-01

    Full Text Available The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection exhibit behavioural changes as (i depression in the tail suspension and forced swim tests, (ii anxiety analysed by elevated plus maze and open field test sand and (iii motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

  17. Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men.

    Science.gov (United States)

    Yokoyama, Akira; Mizukami, Takeshi; Matsui, Toshifumi; Yokoyama, Tetsuji; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

    2013-08-01

    The presence of the less-active form of alcohol dehydrogenase-1B encoded by ADH1B*1/*1 (vs. *2 allele) and active form of aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/*1 (vs. *2 allele) increases the risk of alcoholism in East Asians. The subjects in this cross-sectional survey were 1,902 Japanese alcoholic men (≥40 years) who underwent ADH1B/ALDH2 genotyping. Age-adjusted daily alcohol consumption did not differ according to the ADH1B/ALDH2 genotypes. The age-adjusted odds ratios (AORs; 95% confidence interval) for liver cirrhosis (LC; n = 359, 1.58 [1.19 to 2.09]), chronic calcific pancreatitis (CP; n = 80, 2.24 [1.20 to 4.20]), and diabetes mellitus (DM; n = 383, 1.51 [1.15 to 1.99]) were higher in the ADH1B*2 allele carriers than in the ADH1B*1/*1 carriers. The AORs for LC (1.43 [1.01 to 2.02]), CP (1.68 [0.80 to 3.53]), DM (1.63 [1.15 to 2.30]), and hypertension (HT; n = 495, 1.52 [1.11 to 2.07]) were higher in the ALDH2*1/*1 carriers than in the ALDH2*1/*2 carriers. The ADH1B*2-associated AOR for LC was 2.08 (1.46 to 2.94) among those aged 40 to 59 years, but 0.89 (0.56 to 1.43) among those aged 60 years or over, and the interaction between ADH1B genotype and age on the LC risk was significant (p = 0.009). When the group with non-LC and no/mild fibrosis was used as controls, the ADH1B*2-associated AORs increased according to the severity of their liver disease: 1.67 (1.32 to 2.11) for the group with non-LC and serum type IV collagen values ≥200 ng/ml, 1.81 (1.24 to 2.63) for the group of Child-Pugh class A LC, and 3.17 (1.98 to 5.07) for the group with Child-Pugh class B/C LC. Anti-hepatitis C virus (HCV) antibody was positive in 103 patients, and the groups with a high anti-HCV antibody titer and either the ADH1B*2/*2 genotype or the ALDH2*1/*1 genotype had the highest AORs (8.83 and 4.90, respectively). The population attributable fraction (PAF) due to the ADH1B*2 allele was 29% for LC, 47% for CP, and 27% for DM, and the PAF due to the ALDH2

  18. Novel detection of post-translational modifications in human monocyte-derived dendritic cells after chronic alcohol exposure: Role of inflammation regulator H4K12ac.

    Science.gov (United States)

    Parira, Tiyash; Figueroa, Gloria; Laverde, Alejandra; Casteleiro, Gianna; Gomez Hernandez, Mario E; Fernandez-Lima, Francisco; Agudelo, Marisela

    2017-09-11

    Previous reports on epigenetic mechanisms involved in alcohol abuse have focus on hepatic and neuronal regions, leaving the immune system and specifically monocyte-derived dendritic cells (MDDCs) understudied. Our lab has previously shown histone deacetylases are modulated in cells derived from alcohol users and after in vitro acute alcohol treatment of human MDDCs. In the current study, we developed a novel screening tool using matrix assisted laser desorption ionization-fourier transform-ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS) and single cell imaging flow cytometry to detect post-translational modifications (PTMs) in human MDDCs due to chronic alcohol exposure. Our results demonstrate, for the first time, in vitro chronic alcohol exposure of MDDCs modulates H3 and H4 and induces a significant increase in acetylation at H4K12 (H4K12ac). Moreover, the Tip60/HAT inhibitor, NU9056, was able to block EtOH-induced H4K12ac, enhancing the effect of EtOH on IL-15, RANTES, TGF-β1, and TNF-α cytokines while restoring MCP-2 levels, suggesting that H4K12ac may be playing a major role during inflammation and may serve as an inflammation regulator or a cellular stress response mechanism under chronic alcohol conditions.

  19. Effects of Puerariae Radix Extract on Endotoxin Receptors and TNF-α Expression Induced by Gut-Derived Endotoxin in Chronic Alcoholic Liver Injury

    Directory of Open Access Journals (Sweden)

    Jing-Hua Peng

    2012-01-01

    Full Text Available Kudzu (Pueraria lobata is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine for more than a millennium. However, little is known about its effects on chronic alcoholic liver injury. Therefore, the present study observed the effects of puerariae radix extract (RPE on chronic alcoholic liver injury as well as Kupffer cells (KCs activation to release tumor necrosis factor alpha (TNF-α induced by gut-derived endotoxin in rats and macrophage cell line. RPE was observed to alleviate the pathological changes and lipids deposition in liver tissues as well as the serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, and hepatic gamma-glutamyl transpeptidase (GGT activity. Meanwhile, RPE inhibited KCs activation and subsequent hepatic TNF-α expression and downregulated the protein expression of endotoxin receptors, lipopolysaccharide binding protein (LBP, CD14, Toll-like receptor (TLR 2, and TLR4 in chronic alcohol intake rats. Furthermore, an in vitro study showed that RPE inhibited the expression of TNF-α and endotoxin receptors, CD14 and TLR4, induced by LPS in RAW264.7 cells. In summary, this study demonstrated that RPE mitigated liver damage and lipid deposition induced by chronic alcohol intake in rats, as well as TNF-α release, protein expression of endotoxin receptors in vivo or in vitro.

  20. Housing Interventions and the Chronic and Acute Risks of Family Homelessness: Experimental Evidence for Education.

    Science.gov (United States)

    Cutuli, J J; Herbers, Janette E

    2018-02-21

    This study considers risk associated with family homelessness for school functioning and experimental evidence on the effects of different housing interventions over time. Students in homeless families (N = 172; M age  = 7.31; SD = 4.15) were randomized to housing interventions that focus on acute risks (community-based rapid rehousing), chronic risks (permanent subsidy), or usual care (UC). A matched group of low-income, housed students served as an additional reference for effects on attendance, school mobility, and reading and math achievement across 4 years. Findings partially support the chronic-risk hypothesis that family homelessness interferes with achievement through its relation to deep poverty. Children randomly assigned to UC perform as well or better than children assigned to housing interventions in this municipality. © 2018 The Authors. Child Development © 2018 Society for Research in Child Development, Inc.

  1. White matter injury due to experimental chronic cerebral hypoperfusion is associated with C5 deposition.

    Science.gov (United States)

    Liu, Qinghai; He, Shuhan; Groysman, Leonid; Shaked, David; Russin, Jonathan; Scotton, Thomas C; Cen, Steven; Mack, William J

    2013-01-01

    The C5 complement protein is a potent inflammatory mediator that has been implicated in the pathogenesis of both stroke and neurodegenerative disease. Microvascular failure is proposed as a potential mechanism of injury. Along these lines, this investigation examines the role of C5 in the setting of chronic cerebral hypoperfusion. Following experimental bilateral carotid artery stenosis, C5 protein deposition increases in the corpus callosum over thirty days (pC5 levels do not appear to differ between bilateral carotid artery stenosis and sham-operated mice, implicating a local cerebral process. Following bilateral carotid artery stenosis, C5 deficient mice demonstrate decreased white matter ischemia in the corpus callosum when compared to C5 sufficient controls (pC5 deficient mice exhibit fewer reactive astrocytes and microglia (pC5 complement protein may play a critical role in mediating white matter injury through inflammation in the setting of chronic cerebral hypoperfusion.

  2. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding.

    Science.gov (United States)

    Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S; Calhoun, William J

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to alcoholic lung disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Brain shrinking in chronic alcoholism: CT follow-up study in 65 patients

    Energy Technology Data Exchange (ETDEWEB)

    Schroth, G.; Remmes, U.; Schupmann, A.

    1985-04-01

    CT follow-up studies were done in 65 alcoholics before an inpatient treatment and after a period with confirmed abstinence of 5 weeks duration. The scans were rated 'blind' by linear measurement of well defined distances. An improvement (Significant reduction of brain 'atrophy') was found in 33 patients (50.8%), 5 patients (7,7%) showed a trend towards progression of brain 'atrophy'. The possibility of recovery tends to be significantly greater in younger subjects. These findings and the results of recent MR follow-up studies are consistent with decreased free water during alcohol intoxication and an increase in brain water during alcohol withdrawal.

  4. Death from seizures induced by chronic alcohol abuse--does it exist?

    DEFF Research Database (Denmark)

    Christoffersen, S

    2007-01-01

    In a forensic setting, deaths due to seizures, either epileptic or other, present a well-known problem. Cause of death is rarely established on the basis of physical evidence, but on circumstantial evidence such as tongue biting or discharge of urine or faeces. Seizures have several different...... may die from these seizures. A literature study was performed of deaths due to alcohol-induced seizures, either during withdrawal or as late-onset seizures where the aetiology was established as long time alcohol abuse and a necropsy had shown no other possible cause of death than a seizure. RESULTS......: It was not possible to find any well-documented cases. It is, however, difficult to compare cases in the literature, as there is no generally accepted classification or nomenclature of seizures related to alcohol abuse....

  5. Magnetic resonance imaging of sequelae of central pontine myelinolysis in chronic alcohol abusers

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Kudo, Sho [Department of Radiology, Saga Medical School, 5-1-1 Nabeshima, 849-8501, Saga (Japan); Yuzuriha, Takefumi; Murakami, Masaru; Endoh, Koichi; Hiejima, Shigeto; Koga, Hiroshi [Center for Emotional and Behavional Disorders, Hizen National Hospital, 160 Mitsu, Higashisefuri, Kanzaki, 842-0192, Saga (Japan)

    2003-12-01

    Central pontine myelinolysis (CPM) is one of the serious neurological complications of alcoholism. This study evaluated magnetic resonance images of sequelae of CPM. Approximately 600 alcoholic patients were examined by a 1.0-T magnetic resonance imaging device, and 11 patients were retrospectively found to have a central pontine lesion, a presumed sequela of CPM. The lesions had various shapes and most were cavitary. In 3 of the 11 patients bilateral symmetrical oval lesions were faintly visible in the middle cerebellar peduncles. These middle cerebellar peduncular lesions were diagnosed as having Wallerian degeneration of the pontocerebellar tract secondary to CPM. (orig.)

  6. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Scott W Cousins

    Full Text Available The neovascular (wet form of age-related macular degeneration (AMD leads to vision loss due to choroidal neovascularization (CNV. Since macrophages are important in CNV development, and cytomegalovirus (CMV-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV, laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF, an outcome that requires active virus replication.

  7. [Bilateral corneal ulceration as a result of caloric-protein malnutrition and vitamin A deficit in a patient with chronic alcoholism, chronic pancreatitis and cholecystostomy].

    Science.gov (United States)

    Benítez Cruz, S; Gómez Candela, C; Ruiz Martín, M; Cos Blanco, A I

    2005-01-01

    Since the discovery of vitamins, there has been an increasing interest at relating vitamins with particular diseases. In particular, for vitamin A its singular importance has been determined in multiple vital functions, and its relationship with diseases, both in deficit and in excess, is nowadays completely demonstrated. In developed countries, vitamin deficiency-related diseases have been greatly reduced; however, in some patients with particular features they must be kept in mind. This is the case of a 45 year-old man, with a history of chronic alcoholism, non insulin-dependent diabetes meIlitus and cholecystectomy with a high biliary drainage secondary to emphysematous cholecystitis and perivesicular abscess. He complains of bilateral ocular pain, photophobia, and decreased visual acuity besides a history of pasty, sticky and foul-smelling feces. He is admitted in the Ophthalmology Department and bilateral corneal ulceration is diagnosed. A consultation to the Nutrition Department is made because of cachexia. Severe caloric and mil protein hyponutrition is observed with a BMI of 18.2 and a 23% weight loss for the last 6 months, fat-soluble vitamins (A, D and E) deficit, mild fat malabsorption, and macrocytic and hypochromic anemia. The patient's diet is supplemented with a special hyperproteinic and hypercaloric diet for diabetics, deficient vitamins and pancreatic enzymes to improve absorption are administered, and glycemia is controlled with insulin. Four months later, the patient is assessed and has a BMI of 20, anemia has resolved and from an ophthalmologic viewpoint the course is favorable, the ulcers improve and visual acuity is almost completely recovered. In chronic alcoholic patients with a low dietary intake and clinical complications with nutritional repercussions (pancreatitis that produces malabsorption or cholecystectomy with biliary percutaneous drainage) we should not forget that micronutrients deficits may explain the etiology of other

  8. Alcohol disrupts sleep homeostasis

    Science.gov (United States)

    Thakkar, Mahesh M.; Sharma, Rishi; Sahota, Pradeep

    2014-01-01

    Alcohol is a potent somnogen and one of the most commonly used “over the counter” sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to understand how and where alcohol acts to affect sleep. We have conducted a series of experiments using two different species, rats and mice, as animal models, and a combination of multi-disciplinary experimental methodologies to examine and understand anatomical and cellular substrates mediating the effects of acute and chronic alcohol exposure on sleep-wakefulness. The results of our studies suggest that the sleep-promoting effects of alcohol may be mediated via alcohol’s action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Lesions of the BF cholinergic neurons or blockade of AD A1 receptors results in attenuation of alcohol-induced sleep promotion, suggesting that AD and BF cholinergic neurons are critical for sleep-promoting effects of alcohol. Since binge alcohol consumption is a highly prevalent pattern

  9. Alcohol use, cigarette consumption and chronic post-traumatic stress disorder

    NARCIS (Netherlands)

    Op den Velde, W; Aarts, PGH; Falger, PRJ; Hovens, JE; van Duijn, H; de Groen, JHM; van Duijn, MAJ

    2002-01-01

    Aims: The relationship between alcohol consumption, cigarette smoking and post-traumatic stress disorder (PTSD) was studied in 147 male former members of the civilian resistance against the Nazi occupation of Holland during World War II. Methods: The subjects were interviewed at home. Measures

  10. Effects of chronic heavy alcohol consumption and endurance exercise on cancellous and cortical bone microarchitecture in adult male rats.

    Science.gov (United States)

    Johnson, Teresa L; Gaddini, Gino; Branscum, Adam J; Olson, Dawn A; Caroline-Westerlind, Kim; Turner, Russell T; Iwaniec, Urszula T

    2014-05-01

    Bone health is influenced by numerous lifestyle factors, including diet and exercise. Alcohol is a major nonessential constituent of diet and has dose- and context-dependent effects on bone. Endurance exercise is associated with increased risk of stress fractures. The purpose of this study was to determine the long-term independent and combined effects of chronic heavy alcohol consumption and endurance exercise (treadmill running) on bone mass and microarchitecture in young adult male Sprague-Dawley rats. Six-month-old male rats were randomized into 4 groups (9 to 13 rats/group): sedentary + control diet, sedentary + ethanol (EtOH) diet, exercise + control diet, or exercise + EtOH diet. EtOH-fed rats consumed a liquid diet (EtOH comprised 35% of caloric intake) ad libitum. Control rats were pair-fed the same diet with isocaloric substitution of EtOH with maltose-dextran. Exercise was conducted on a motorized treadmill (15% grade for 30 minutes) 5 d/wk for 16 weeks. Femur and 12th thoracic vertebra were analyzed for bone mineral content (BMC) and density (BMD) using densitometry and cortical and cancellous bone architecture using microcomputed tomography. EtOH consumption resulted in lower femur length, BMC, and BMD, and lower midshaft femur cortical volume, cortical thickness, and polar moment of inertia. In addition, trabecular thickness was lower in vertebra of EtOH-fed rats. Endurance exercise had no independent effect on any end point evaluated. A significant interaction between endurance exercise and EtOH was detected for several cancellous end points in the distal femur metaphysis. EtOH-consuming rats that exercised had lower distal femur metaphysis bone volume/tissue volume, trabecular connectivity density, and trabecular thickness compared to exercising rats that consumed control diet. The results obtained in this model suggest that chronic heavy alcohol consumption may reduce skeletal integrity by reducing bone size, mass, and density, and by negatively

  11. Chronic Generalized Harassment during College: Influences on Alcohol and Drug Use

    OpenAIRE

    McGinley, Meredith; Rospenda, Kathleen M.; Liu, Li; Richman, Judith A.

    2015-01-01

    The experience of chronic generalized harassment from others can have a deleterious impact on individuals over time. Specifically, coping resources may be taxed, resulting in the use of avoidant coping strategies such substance use. However, little is known about the experience of chronic generalized harassment (e.g., verbal hostility, manipulation by others, exclusion from important events) and its impact on substance use in collegiate populations. In the current study, we examined the laten...

  12. Intravitreal implantation of the biodegradable cyclosporin A drug delivery system for experimental chronic uveitis.

    Science.gov (United States)

    Dong, Xiaoguang; Shi, Weiyun; Yuan, Gongqiang; Xie, Lixin; Wang, Shenguo; Lin, Ping

    2006-04-01

    The purpose was to evaluate the efficacy of the intravitreal implantation of the biodegradable cyclosporin A (CsA) drug delivery system (DDS) for experimental chronic uveitis. The DDS was prepared by formulating CsA into glycolide-co-lactide-co-caprolactone copolymer (PGLC). Right eyes of 30 New Zealand white rabbits were used to establish a model of uveitis and randomized into control, intravitreal non-medicated DDS, oral CsA (15 mg/kg daily), and intravitreal CsA-PGLC DDS (each containing 2 mg CsA) groups. The progress of ocular inflammation, results of electroretinography, and histopathological examination of ocular, renal, and hepatic functions were recorded. Intravitreal CsA levels were measured in another 13 rabbits receiving an implant of the CsA-PGLC DDS. Chronic uveitis was successfully induced in all 30 eyes. The inflammation in the eyes with no treatment, non-medicated implant, and oral CsA was more severe than those with the CsA-PGLC DDS at each timepoint. The electroretinography b-wave was depressed much less in the CsA-PGLC DDS group than in the other three groups (ptoxicity was detected. Intravitreal implantation of the biodegradable CsA-PGLC DDS may effectively reduce the intraocular inflammation in rabbits with no toxicity, which provides a potentially safe and convenient approach for the treatment of chronic uveitis.

  13. Quantitative analysis of collagen and collagen subtypes I, III, and V in human pancreatic cancer, tumor-associated chronic pancreatitis, and alcoholic chronic pancreatitis.

    Science.gov (United States)

    Imamura, T; Iguchi, H; Manabe, T; Ohshio, G; Yoshimura, T; Wang, Z H; Suwa, H; Ishigami, S; Imamura, M

    1995-11-01

    The collagen content in human pancreatic cancer tissue, tissue of tumor-associated chronic pancreatitis (TACP), and normal pancreatic tissue was determined in 14 patients with pancreatic cancer by measuring the amount of 4-hydroxyproline. Four patients with alcoholic chronic pancreatitis (AlCP) were also analyzed. The mean collagen content in both pancreatic cancer tissue and TACP tissue was approximately threefold higher than in normal pancreatic tissue. Cyanogen bromide peptides of type I, III, and V collagens from invasive ductal carcinomatous tissue of the pancreas and from TACP tissue of eight patients were analyzed sequentially using high-performance liquid chromatography with ion-exchange and gel-permeation columns. No difference in the proportion of type I, III, and V collagens was detected between pancreatic cancer tissue and TACP tissue. The mean collagen content in AlCP tissue was significantly lower than that in TACP tissue, but no difference in the proportion of type I, III, and V collagens was detected between these two tissues. These results indicate a similar quantity and distribution pattern of fibrillar collagen in human pancreatic cancer and TACP.

  14. Experimentally derived acute and chronic copper Biotic Ligand Models for rainbow trout.

    Science.gov (United States)

    Crémazy, Anne; Wood, Chris M; Ng, Tania Y-T; Smith, D Scott; Chowdhury, M Jasim

    2017-11-01

    with the pH. Additional mechanistic studies are required to understand the influence of pH, Na, and Mg on Cu toxicity to trout. The present study presents the first experimentally developed chronic Cu BLM for the rainbow trout. To the best of our knowledge, it also presents the first acute Cu BLM that is based on a published data-set for trout. These newly developed BLMs should contribute to improving the risk assessment of Cu to fish in freshwater. Copyright © 2017. Published by Elsevier B.V.

  15. Decoding of emotional components in complex communicative situations (irony) and its relation to empathic abilities in male chronic alcoholics: an issue for treatment.

    Science.gov (United States)

    Amenta, Simona; Noël, Xavier; Verbanck, Paul; Campanella, Salvatore

    2013-02-01

    Previous research has shown that deficits in the domain of emotions strongly characterize alcoholism. Patients diagnosed with alcoholism show impairments in emotional mimic recognition, as well as in the domain of emotional prosody. These data suggest that male alcoholics might suffer from a generalized emotional impairment associated with dysfunctions in empathy. Taken altogether, those deficits might influence alcoholics' relational domain and their performance in complex communicative situations such as ironic interactions. The present study investigates the ability of chronic male alcoholics to recognize the emotional component of ironic contexts and its relation to the comprehension of ironic meaning as a function of their empathic abilities. Forty-four male subjects participated in a story comprehension task. They were asked to read stories with either an ironic or a nonironic ending. Participants were asked to fill in a questionnaire about communicative intentions and the emotional states of the stories' characters. Moreover, the correct comprehension of the ironic meaning was assessed through a self-reported questionnaire and related to the empathy quotient (EQ) which was measured in a preexperimental phase. Alcoholic subjects showed a lower EQ in comparison to healthy subjects and recognized significant fewer ironic endings. Social skills results were particularly impaired. The correlation between EQ and ironic endings recognition was significant. Moreover, alcoholics showed a tendency to attribute positive emotions to both ironic and nonironic contexts, showing an opposite pattern in comparison with control subjects who tended to associate negative emotions to ironic contexts. The present study indicates that emotional recognition deficits that have been previously observed in chronic alcoholics extend to complex interactive contexts. This deficit is associated with a more general impairment of empathy, especially in its social skill component. Clinical

  16. Alcoholic cardiomyopathy

    OpenAIRE

    Maisch, B.

    2016-01-01

    The individual amount of alcohol consumed acutely or chronically decides on harm or benefit to a person?s health. Available data suggest that one to two drinks in men and one drink in women will benefit the cardiovascular system over time, one drink being 17.6?ml 100?% alcohol. Moderate drinking can reduce the incidence and mortality of coronary artery disease, heart failure, diabetes, ischemic and hemorrhagic stroke. More than this amount can lead to alcoholic cardiomyopathy, which is define...

  17. [Invasive pulmonary aspergillosis and esophageal candidiasis in a patient with decompensated liver cirrhosis due to chronic hepatitis C and alcohol].

    Science.gov (United States)

    Porubčin, Štefan; Porubčinová, I; Kristian, P; Virág, L; Štammová, E; Vyhnánková, V; Paraličová, Z

    2012-02-01

    We present a rare case of combined fungal infection in a critically ill 47 year-old patient with chronic hepatitis C at the stage of liver cirrhosis. The patient was admitted for signs of decompensated cirrhosis caused by hepatitis C and increased alcohol consumption. After 2 week hospital stay, his condition was complicated by a pulmonary infiltrate and rapid deterioration followed. Despite intensive care, the patient died. Autopsy findings showed invasive pulmonary aspergillosis. The aim of this case report is to point to a broad differential diagnosis of jaundice and pulmonary infiltrates, thus stressing the value of interdisciplinary cooperation and the need to consider the possibility of invasive fungal infections when caring for liver cirrhosis patients. In addition, several risk factors contributing to the development of fungal diseases in these patients are discussed in the article.

  18. Experience of Using Mineral Water in the Treatment of Patients with Chronic Viral Hepatitis C with Concomitant Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    N.V. Dragomyretska

    2016-02-01

    Full Text Available The paper proved the feasibility of a course of mineral water intake (in double dosing regimen in combination treatment of patients with chronic viral hepatitis C and concomitant non-alcoholic fatty liver disease in order to improve the clinical course of the underlying disease and comorbidity, to restore the functional state of the liver, to reduce insulin resistance.

  19. Aging, chronic alcohol consumption, and low folate intake are determinants of genomic DNA methylation in the liver and colon of mice

    Science.gov (United States)

    Advanced age and chronic alcohol consumption are important risk factors in the development of colon and liver cancer. Both factors are known to be associated with altered DNA methylation. Inadequate folate intake can also derange biological methylation pathways. We investigated the effects of aging,...

  20. Alcohol use disorders and associated chronic disease - a national retrospective cohort study from France.

    Science.gov (United States)

    Schwarzinger, Michaël; Thiébaut, Sophie Pascale; Baillot, Sylvain; Mallet, Vincent; Rehm, Jürgen

    2017-07-21

    Evidence on diseases caused by or associated with alcohol use disorders (AUDs) has been based on two meta-analyses including rather dated studies. The objective of this contribution was to estimate the risks of all-cause mortality and alcohol-attributable disease categories depending on a diagnosis of AUDs in a national sample for France. In a national retrospective cohort study on all inpatient acute and rehabilitation care patients in Metropolitan France 2008-2012 (N = 26,356,361), AUDs and other disease categories were identified from all discharge diagnoses according to standard definitions, and we relied on in-hospital death for mortality (57.4% of all deaths). 704,803 (2.7%) patients identified with AUDs had a threefold higher risk of death (HR = 2.98; 95% CI: 2.96-3.00) and died on average 12.2 years younger (men: 10.4, 95% CI: 10.3-10.5; women: 13.7, 95% CI: 13.6-13.9). AUDs were associated with significantly higher risks of hospital admission for all alcohol-attributable disease categories: digestive diseases, cancers (exception: breast cancer), cardiovascular diseases, dementia, infectious diseases, and injuries. Elevated risks were highest for liver diseases that were associated with about two-third of deaths in patients with AUDs (men: 64.3%; women: 71.1%). AUDs were associated with marked premature mortality and higher risks of alcohol-attributable disease categories. Our results support the urgent need of measures to reduce the burden of AUDs.

  1. Radiological changes in the region of the patella in chronic alcoholics

    Energy Technology Data Exchange (ETDEWEB)

    Szanto, D.

    1982-07-01

    The author has reviewed the changes in the patello-femoral joint seen on plain films in 41 male alcoholics. These are due to the effect of hyperlipoproteinaemia type IV on the patello-femoral joint. These joints show bilateral secondary arthrosis. At the same time as these erosions and defects of the articular surface develop, there are also changes in the femoro-tibial joint.

  2. [Application of operant conditioning techniques to forensic toxicology: experimental studies on alcohol and abusable drugs].

    Science.gov (United States)

    Hishida, S

    1996-10-01

    This paper describes some experiments that apply the operant conditioning techniques to forensic toxicological research. These techniques may be useful in investigating the mechanisms of action, toxic symptoms, legal competence and drug metabolism associated with substance abuse such as abuse of alcohol, psychotropic drugs, narcotics, stimulants, and organic solvents. 1) Genetic research on alcohol preference in rats. We applied operant conditioning to investigate alcohol preference in rats and constructed an apparatus for the measurement of discriminated operate responses for water or alcohol reinforcement in rat. This apparatus is a modified Skinner box with a one-lever two-liquid system. Fixed ratio-10 (FR-10) schedules of reinforcement are used to increase the work of the rat before it obtains the reinforcement. The voluntary choice of water or 10% ethanol by the rat can be assessed quantitatively by measuring the lever-pushing responses. It is an extremely useful method for measuring the real alcohol preference of rats. A rat was kept in a Skinner box overnight. The numbers of responses and reinforcement for water and ethanol and the volumes of the two liquids consumed were recorded. The ratio of ethanol reinforcement was defined as the number of ethanol reinforcement to the total number of ethanol and water reinforcement. The ratio of ethanol intake was defined as the volume of ethanol consumed to the volume of water and ethanol consumed. Ethanol consumption per g body weight was calculated from the volume of ethanol consumed by the rat. We used this apparatus to investigate alcohol preference of more than 300 Wistar Albino Rats, and divided them into a high alcohol preference (HAP) group and a low alcohol preference (LAP) group. Inbreeding between littermates was conducted in each of the HAP and LAP groups. The liver tissue of each offspring was obtained and the cytosol fraction was collected and subjected to isoelectric focusing using polyacrylamide gel

  3. Evaluation of Anti-diarrheal Potential of Hydro-alcoholic Extracts of Leaves of Murraya koenigii in Experimental Animals.

    Science.gov (United States)

    Ramasamy, Anand; Das, Saibal; Mani, Vasudevan; Sengottuvelu, S; Vinoth Prabhu, V

    2016-01-01

    The indigenous medical system of India mentions the use of Murraya koenigii leaves for the treatment of different types of diarrheas over ages. To evaluate the anti-diarrheal activity of hydro-alcoholic extracts of leaves of Murraya koenigii and to check its effects on intestinal transits in experimental rat model. The hydro-alcoholic extract of Murraya koenigii leaves was obtained with Soxhlet extraction method. Animals were divided into four groups (n = 6) receiving daily for three consecutive days: vehicle, standard drug atropine (3mg/kg, i.p.), leaf extracts 200 & 400 mg/kg respectively in oral route. Effects of the drugs on normal defecation were noted and then castor oil induced diarrhea was used to measure the effects of leaf extract on stool frequency and consistency. Finally, charcoal meal test was used to evaluate the effect of the extract on intestinal transit. Statistical evaluation was done using SPSS version 17, one way ANOVA followed by Dunnett's t-test was done and PMurraya koenigii leaf extracts in 200 and 400 mg/kg dose reduced stool frequency, increased stool consistency and increased small intestinal transit time. Hydro-alcoholic extract of Murraya koenigii leaves possesses significant anti-diarrheal activity due to its inhibitory effect on gastrointestinal motility, making it useful for a wide number of gastrointestinal diseases.

  4. [Forensic medical diagnostics of chronic alcoholic intoxication based on histological changes in the soft tissues of oral cavity and salivary glands].

    Science.gov (United States)

    Pigolkin, Iu I; Dolzhanskiĭ, O V; Mamsurova, T S; Chertovskikh, A A

    2011-01-01

    Histological studies of oral cavity mucosa and salivary glands in subjects with chronic alcoholic intoxication revealed changes at the surface of the tongue and in the glandular tissues. Specific features of chronic alcoholic intoxication include acinar and ductal hyperplasia, reduction of the adipose tissue mass in salivary gland stroma, predominance of T-lymphocytes in hard palate minor salivary glands and B-lymphocytes in the stroma of labial minor salivary gland, the absence of plasma cells in the stroma of hard palate minor salivary glands and labial mucosa. Leukoplakia, dysplasia, and hyperplasia of the basal epithelial layer of oral cavity mucosa are considered to be the signs of long-term (over 12 months) alcohol consumption.

  5. Quantitative analysis of the nanoscale intra-nuclear structural alterations in hippocampal cells in chronic alcoholism via transmission electron microscopy study

    CERN Document Server

    Sahay, Peeyush; Ghimire, Hemendra M; Almabadi, Huda; Tripathi, Vibha; Mohanty, Samarendra K; Rao, Radhakrishna; Pradhan, Prabhakar

    2015-01-01

    Chronic alcoholism is known to alter morphology of hippocampal, an important region of cognitive function in the brain. We performed quantification of nanoscale structural alterations in nuclei of hippocampal neuron cells due to chronic alcoholism, in mice model. Transmission electron microscopy images of the neuron cells were obtained and the degrees of structural alteration, in terms of mass density fluctuations, were determined using the recently developed light localization analysis technique. The results, obtained at the length scales ranging from 33 to 195 nm, show that the 4-week alcohol fed mice have higher degree of structural alteration in comparison to the control mice. The degree of structural alterations starts becoming significantly distinguishable around 100 nm sample length, which is the typical length scale of the building blocks of cells, such as DNA, RNA, etc. Different degrees of structural alterations at such length scales suggest possible structural rearrangement of chromatin inside the ...

  6. Alcohol consumption and sudden unexpected death in epilepsy: experimental approach Consumo de álcool e morte súbita em epilepsia: uma abordagem experimental

    Directory of Open Access Journals (Sweden)

    Carla A. ScorzaI

    2009-12-01

    Full Text Available Using the pilocarpine model of epilepsy, we investigated the effects of alcohol consumption on the frequency of seizures in animals with epilepsy as well the underlying a possible association between alcohol intake and sudden unexpected death in epilepsy (SUDEP occurrence. Rats were divided randomly into two groups: (A rats with epilepsy and (B rats with epilepsy that received a daily dose of ethanol solution (350 mg kg-1, i.p. for 30 days. The basal frequency of seizures observed in the A and B groups during the first 30 days were 3.4±1.5 and 3.2±1.9 seizures per week per animal, respectively. In B group, it was observed a significant seizure increase (11.6±5.3 during the first 2 weeks of alcohol administration and quite interesting, one rat died suddenly after a generalized tonic-clonic seizure during this period. We concluded in our experimental study that exist a possible association between alcohol abuse and SUDEP occurrence.Utilizando o modelo de epilepsia induzido pela pilocarpina, investigamos os efeitos do consumo de álcool sobre a frequência de crises epilépticas em animais com epilepsia, como também uma possível associação entre a ingestão de álcool e ocorrência de morte súbita e inesperada nas epilepsias (SUDEP. Os animais foram randomicamente divididos em dois grupos: (A ratos com epilepsia e (B ratos com epilepsia que receberam uma dose diária de etanol (350 mg kg-1, i.p. por 30 dias consecutivos. A frequência basal de crises epilépticas observadas nos grupos A e B durante os primeiros 30 dias foram de 3,4±1,5 e 3,2±1,9 crises por semana/animal, respectivamente. No grupo B, ocorreu aumento significativo na frequência de crises (11,6±5,3 durante as duas primeiras semanas de administração do álcool e de forma interessante, um animal morreu subitamente após uma crise generalizada tônico-clonica durante esse período. Concluímos em nossa abordagem experimental que existe uma possível associação entre o

  7. Experimental chronic entrapment of the sciatic nerve in adult hamsters: an ultrastructural and morphometric study

    Directory of Open Access Journals (Sweden)

    Prinz R.A.D.

    2003-01-01

    Full Text Available Entrapment neuropathy is a group of clinical disorders involving compression of a peripheral nerve and interference with nerve function mostly through traction injury. We have investigated the chronic compression of peripheral nerves as an experimental procedure for detecting changes in ultrastructural nerve morphology. Adult hamsters (Mesocricetus auratus, N = 30 were anesthetized with a 25% pentobarbital solution and received a cuff around the right sciatic nerve. Left sciatic nerves were not operated (control group. Animals survived for varying times (up to 15 weeks, after which they were sacrificed and both sciatic nerves were immediately fixed with a paraformaldehyde solution. Experimental nerves were divided into segments based upon their distance from the site of compression (proximal, entrapment and distal. Semithin and ultrathin sections were obtained and examined by light and electron microscopy. Ultrastructural changes were qualitatively described and data from semithin sections were morphometrically analyzed both in control and in compressed nerves. We observed endoneurial edema along with both perineurial and endoneurial thickening and also the existence of whorled cell-sparse structures (Renaut bodies in the subperineurial space of compressed sciatic nerves. Morphometric analyses of myelinated axons at the compression sites displayed a remarkable increase in the number of small axons (up to 60% in comparison with the control axonal number. The distal segment of compressed nerves presented a distinct decrease in axon number (up to 40% comparatively to the control group. The present experimental model of nerve entrapment in adult hamsters was shown to promote consistent histopathologic alterations analogous to those found in chronic compressive neuropathies.

  8. Co-occurring patterns of smoking and alcohol consumption among Korean adolescents.

    Science.gov (United States)

    Chung, Ick-Joong; Chun, Jongserl

    2010-01-01

    This study seeks to assess the transition probabilities between smoking and alcohol consumption trajectories for ages 13-17 using data from the Korea Youth Panel Survey (KYPS). Four smoking trajectories were identified-noninitiator, late-onsetter, experimenter, and escalator. Similarly, four alcohol consumption trajectories were identified-noninitiator, late-onsetter, experimenter, and chronic user. Those in the chronic group of alcohol consumption were most likely to be smokers. Those who fell into a particular group for use of one substance were most likely to fall into the corresponding group for use of the other substance. Implications for smoking and alcohol prevention are discussed.

  9. Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis.

    Science.gov (United States)

    Zhang, Liping; Kline, Robert H; McNearney, Terry A; Johnson, Michael P; Westlund, Karin N

    2014-11-17

    Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in several studies with inflammatory and neuropathic preclinical pain models. In this study, the analgesic efficacy of a novel, highly selective CB2 receptor agonist, LY3038404 HCl, is investigated in a chronic pancreatitis pain model, induced with an alcohol/high fat (AHF) diet. Rats fed the AHF diet developed visceral pain-like behaviors detectable by week 3 and reached a maximum at week 5 that persists as long as the diet is maintained. Rats with AHF induced chronic pancreatitis were treated with LY3038404 HCl (10 mg/kg, orally, twice a day for 9 days). The treated animals demonstrated significantly alleviated pain related behaviors after 3 days of dosing, including increased paw withdrawal thresholds (PWT), prolonged abdominal withdrawal latencies (ABWL), and decreased nocifensive responses to noxious 44°C hotplate stimuli. Terminal histological analysis of pancreatic tissue sections from the AHF chronic pancreatitis animals demonstrated extensive injury, including a global pancreatic gland degeneration (cellular atrophy), vacuolization (fat deposition), and fibrosis. After the LY3038404 HCl treatment, pancreatic tissue was significantly protected from severe damage and fibrosis. LY3038404 HCl affected neither open field exploratory behaviors nor dark/light box preferences as measures

  10. Relationship of coping and patterns of dependent behavior in patients with chronic pancreatitis of biliary and alcoholic etiology in aspect of differentiation of its medical and psychological support

    Directory of Open Access Journals (Sweden)

    Маріанна Владиславівна Маркова

    2015-08-01

    Full Text Available Choric pancreatitis is an actual medical and psychological problem in Ukraine. The aim of the work was to study the features of coping in patients with chronic pancreatitis of alcoholic and biliary etiology.Methods. For detecting coping-mechanisms the standard method WCQ Р of Lazarus was used. The study of addictive tendencies was carried out with the help of questionnaire AUDIT and UDIT-tests oriented on patterns of dependent behavior.Results. The study of features of coping-mechanisms and an addiction to dependent behavior in patients with chronic pancreatitis revealed intergroup and intragroup differences. Confrontation and low levels of self-control, responsibility and positive assessment were intrinsic for respondents with alcoholic etiology of pancreatitis. Women demonstrated the high addiction to the search of social support, men – to distancing. As to an addictive behavior there was revealed that the typical common tendencies were the consumption of coffee, alcohol, internet-dependence, the specific ones for women – TV, shopping-dependencies, for men – workaholism in patients with biliary and computer-addiction in patients with alcoholic chronic pancreatitis. Intergroup differences were demonstrated by an addiction to disorder of food behavior in patients with biliary and consumption of alcohol and smoking in respondents with alcoholic etiology of pancreatitis.Conclusions. The revealed differences in coping-strategies of patients with different nosological forms of chronic pancreatitis give important information for detecting the targets of medical and psychological influence and constructing of differentiated program of medical and psychological help to patients of this type

  11. Current hypotheses on the mechanisms of alcoholism.

    Science.gov (United States)

    Vetreno, R P; Crews, F T

    2014-01-01

    Chronic use of alcohol results in progressive changes to brain and behavior that often lead to the development of alcohol dependence and alcoholism. Although the mechanisms underlying the development of alcoholism remain to be fully elucidated, diminished executive functioning due to hypoactive prefrontal cortex executive control and hyperactive limbic system anxiety and negative emotion might contribute mechanistically to the shift from experimental use to alcoholism and dependence. In the chapter that follows, behavioral deficits associated with cortical dysfunction and neurodegeneration will be related to the behavioral characteristics of alcoholism (e.g., diminished executive function, impulsivity, altered limbic modulation). We will provide evidence that alterations in cyclic AMP-responsive element binding protein (CREB: neurotrophic) and NF-κB (neuroimmune) signaling contribute to the development and persistence of alcoholism. In addition, genetic predispositions and an earlier age of drinking onset will be discussed as contributing factors to the development of alcohol dependence and alcoholism. Overall chronic ethanol-induced neuroimmune gene induction is proposed to alter limbic and frontal neuronal networks contributing to the development and persistence of alcoholism. © 2014 Elsevier B.V. All rights reserved.

  12. What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels.

    Science.gov (United States)

    Nichols, Melanie; Scarborough, Peter; Allender, Steven; Rayner, Mike

    2012-01-01

    To estimate the impact of achieving alternative average population alcohol consumption levels on chronic disease mortality in England. A macro-simulation model was built to simultaneously estimate the number of deaths from coronary heart disease, stroke, hypertensive disease, diabetes, liver cirrhosis, epilepsy and five cancers that would be averted or delayed annually as a result of changes in alcohol consumption among English adults. Counterfactual scenarios assessed the impact on alcohol-related mortalities of changing (1) the median alcohol consumption of drinkers and (2) the percentage of non-drinkers. Risk relationships were drawn from published meta-analyses. Age- and sex-specific distributions of alcohol consumption (grams per day) for the English population in 2006 were drawn from the General Household Survey 2006, and age-, sex- and cause-specific mortality data for 2006 were provided by the Office for National Statistics. The optimum median consumption level for drinkers in the model was 5 g/day (about half a unit), which would avert or delay 4579 (2544 to 6590) deaths per year. Approximately equal numbers of deaths from cancers and liver disease would be delayed or averted (∼2800 for each), while there was a small increase in cardiovascular mortality. The model showed no benefit in terms of reduced mortality when the proportion of non-drinkers in the population was increased. Current government recommendations for alcohol consumption are well above the level likely to minimise chronic disease. Public health targets should aim for a reduction in population alcohol consumption in order to reduce chronic disease mortality.

  13. Alcohol myopia and goal commitment

    Directory of Open Access Journals (Sweden)

    A. Timur Sevincer

    2014-03-01

    Full Text Available According to alcohol-myopia theory, acute alcohol consumption leads people to disproportionally focus on the salient rather than the peripheral aspects of a situation. We summarize various studies exploring how myopic processes resulting from acute alcohol intake affect goal commitment. After consuming alcohol student participants felt strongly committed to an important personal goal even though they had low expectations of successfully attaining the goal. However, once intoxicated participants were sober again (i.e., not myopic anymore they failed to act on their goal commitment. In line with alcohol-myopia theory, strong goal commitment as a result of alcohol intake was mediated by intoxicated (vs. sober participants disproportionally focusing on the desirability rather than the feasibility of their goal. Further supporting alcohol-myopia theory, when the low feasibility of attaining a particular goal was experimentally made salient (either explicitly or implicitly by subliminal priming, intoxicated participants felt less committed than those who consumed a placebo. We discuss these effects of acute alcohol intake in the context of research on the effects of chronic alcohol consumption on goal commitment.

  14. Experimental use of Olomouc test of figural fluency in people addicted to alcohol

    Directory of Open Access Journals (Sweden)

    Martin Lečbych

    2014-12-01

    Full Text Available Problem: The study of cognitive deficits in patients who are addicted to alcohol is an important topic of contemporary research. Several studies demonstrate that for this group of patients is typical diffused cognitive deficit that impairs more cognitive abilities including executive functions. Recent researches shows that executive dysfunctions among this patients is connected with poor therapeutic prognosis and coping with alcohol addiction. Diagnostic of executive functions among this group is often underestimated. Our aim in this study is to assess executive function among this group of patients by new Olomouc test of figural fluency that is intended for measurement of executive functioning and comparing their results with control group. Methods: We assess performance of 44 patients with alcohol dependence syndrome and 146 volunteers in control group with Olomouc test of figural fluency. We refer about main specific of this method compared to other tools for assessing of figural fluency. Selection of all participants in both groups was voluntary and based on their motivation. Results: We found that clinical and control group differ statistically significantly in overall numbers of produced designs (CP, in overall numbers of unique designs (CV and in the index of precision of their work (V/P. The main test criterion (number of unique designs, CV shows as a most powerful and useful in differentiation of both groups from statistical (t=-4,73; p < 0,01 and practical points of view (effect size d=0,86. Discussion: Our research findings correspond with recent research studies about executive deficit among group of patients addicted to alcohol and overall poor performance in executive tasks. We considered that number of unique designs produced in Olomouc test of figural fluency should be important criterion for discrimination between research and control group. For prediction of impact of executive deficit to coping with addiction is further

  15. Effects of restricted environmental stimulation: enhancement of hypnotizability for experimental and chronic pain control.

    Science.gov (United States)

    Barabasz, A F; Barabasz, M

    1989-07-01

    Enhancement of hypnotizability and pain tolerance has been demonstrated using restricted environmental stimulation therapy (REST) with university students as Ss (A. F. Barabasz, 1982). The purpose of the present study was to determine whether or not similar results could be obtained with chronic pain patients. Ss consisted of outpatients in treatment for conditions in which pain is prominent who also demonstrated low hypnotizability after repeated hypnosis plateau sessions. 2 groups of Ss were exposed to REST. Situational demand characteristics (Orne, 1962) favored an increase in hypnotizability for REST Group 1 (high demand). REST Group 2 (low demand) was exposed to situational demand characteristics designed to disguise the experimental hypothesis. 2 groups of control Ss were exposed to the same alternative demand characteristic manipulations as the experimental groups, but environmental stimulation was maintained. The Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) of Weitzenhoffer and E. R. Hilgard (1962), including a posthypnotic suggestion for an anesthetic reaction, and an ischemic pain test were administered prior to treatment and again immediately following treatment. After 6 hours of REST, significant increases in SHSS:C scores were found for high-demand and low-demand experimental Ss, as well as for high-demand control Ss. No such increase was found for low-demand controls. Significant decreases in pain scores were found for both high- and low-demand experimental groups. No significant pain score decreases were found for either control group, suggesting a relatively weak effect of demand characteristics. An independent postexperimental inquiry suggested all Ss believed they received active treatments. The inquiry, conducted 10-15 days after the experiment, also revealed a majority of experimental Ss were using hypnosis on a daily basis to reduce pain with a substantial decrease in pain medication. Only 2 control Ss (highest in hypnotizability

  16. Experimental and clinical usefulness of crossmodal paradigms in psychiatry: An illustration from emotional processing in alcohol-dependence.

    Directory of Open Access Journals (Sweden)

    Pierre eMaurage

    2013-07-01

    Full Text Available Cross-modal processing (i.e., the construction of a unified representation stemming from distinct sensorial modalities inputs constitutes a crucial ability in humans’ everyday life. It has been extensively explored at cognitive and cerebral levels during the last decade among healthy controls. Paradoxically however, and while difficulties to perform this integrative process have been suggested in a large range of psychopathological states (e.g., schizophrenia and autism, these cross-modal paradigms have been very rarely used in the exploration of psychiatric populations. The main aim of the present paper is thus to underline the experimental and clinical usefulness of exploring cross-modal processes in psychiatry. We will illustrate this proposal by means of the recent data obtained in the cross-modal exploration of emotional alterations in alcohol-dependence. Indeed, emotional decoding impairments might have a role in the development and maintenance of alcohol-dependence, and have been extensively investigated by means of experiments using separated visual or auditory stimulations. Besides these unimodal explorations, we have recently conducted several studies using audio-visual cross-modal paradigms, which has allowed us to improve the ecological validity of the unimodal experimental designs and to offer new insights on the emotional alterations among alcohol-dependent individuals. We will show how these preliminary results can be extended to develop a coherent and ambitious research program using cross-modal designs in various psychiatric populations and sensory modalities. We will finally end the paper by underlining the various potential clinical applications and the fundamental implications that can be raised by this emerging project.

  17. Experimental and clinical usefulness of crossmodal paradigms in psychiatry: an illustration from emotional processing in alcohol-dependence

    Science.gov (United States)

    Maurage, Pierre; Campanella, Salvatore

    2013-01-01

    Crossmodal processing (i.e., the construction of a unified representation stemming from distinct sensorial modalities inputs) constitutes a crucial ability in humans' everyday life. It has been extensively explored at cognitive and cerebral levels during the last decade among healthy controls. Paradoxically however, and while difficulties to perform this integrative process have been suggested in a large range of psychopathological states (e.g., schizophrenia and autism), these crossmodal paradigms have been very rarely used in the exploration of psychiatric populations. The main aim of the present paper is thus to underline the experimental and clinical usefulness of exploring crossmodal processes in psychiatry. We will illustrate this proposal by means of the recent data obtained in the crossmodal exploration of emotional alterations in alcohol-dependence. Indeed, emotional decoding impairments might have a role in the development and maintenance of alcohol-dependence, and have been extensively investigated by means of experiments using separated visual or auditory stimulations. Besides these unimodal explorations, we have recently conducted several studies using audio-visual crossmodal paradigms, which has allowed us to improve the ecological validity of the unimodal experimental designs and to offer new insights on the emotional alterations among alcohol-dependent individuals. We will show how these preliminary results can be extended to develop a coherent and ambitious research program using crossmodal designs in various psychiatric populations and sensory modalities. We will finally end the paper by underlining the various potential clinical applications and the fundamental implications that can be raised by this emerging project. PMID:23898250

  18. Quality of life in patients with depression, panic syndrome, other anxiety syndrome, alcoholism and chronic somatic diseases: a longitudinal study in Slovenian primary care patients.

    Science.gov (United States)

    Cerne, Anja; Rifel, Janez; Rotar-Pavlic, Danica; Svab, Igor; Selic, Polona; Kersnik, Janko

    2013-01-01

    To analyse the correlates between the quality of life and chronic diseases and socio-demographic characteristics of patients in family medicine with a special emphasis on depression, panic syndrome, other anxiety syndrome and alcoholism. In a longitudinal study, the data set of 516 family practice attendees recruited from 60 family practices was analysed. Depression, panic syndrome, other anxiety syndrome and alcoholism were diagnosed using appropriate diagnostic interviews. Quality of life was assessed using the SF-12 questionnaire, measuring a mental health score and a physical health score. Data about the number of chronic somatic diseases were obtained from the patients' medical records. Physical health score was negatively associated with higher age (β = -0.25, p panic syndrome (β = -0.07, p panic syndrome and number of chronic somatic diseases as they are associated with poorer quality of life.

  19. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B

    2004-01-01

    Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the circ...

  20. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B

    2004-01-01

    BACKGROUND: Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evalu...

  1. Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure.

    Science.gov (United States)

    Repunte-Canonigo, Vez; Lutjens, Robert; van der Stap, Lena D; Sanna, Pietro Paolo

    2007-03-23

    Intermittent models of alcohol exposure that mimic human patterns of alcohol consumption produce profound physiological and biochemical changes and induce rapid increases in alcohol self-administration. We used high-density oligonucleotide microarrays to investigate gene expression changes during chronic intermittent alcohol exposure in three brain regions that receive mesocorticolimbic dopaminergic projections and that are believed to be involved in alcohol's reinforcing actions: the medial prefrontal cortex, the nucleus accumbens and the amygdala. An independent replication of the experiment was used for RT-PCR validation of the microarray results. The protein kinase A inhibitor alpha (PKI-alpha, Pkia), a member of the endogenous PKI family implicated in reducing nuclear PKA activity, was found to be increased in all three regions tested. Conversely, we observed a downregulation of the expression of several PKA-regulated transcripts in one or more of the brain regions studied, including the activity and neurotransmitter-regulated early gene (Ania) - 1, -3, -7, -8, the transcription factors Egr1 and NGFI-B (Nr4a1) and the neuropeptide NPY. Reduced expression of PKA-regulated genes in mesocorticolimbic projection areas may have motivational significance in the rapid increase in alcohol self-administration induced by intermittent alcohol exposure.

  2. Evaluation of chronic alcohol self-administration by a 3-bottle choice paradigm in adult male rats. Effects on behavioural reactivity, spatial learning and reference memory.

    Science.gov (United States)

    Cacace, Silvana; Plescia, Fulvio; La Barbera, Marco; Cannizzaro, Carla

    2011-06-01

    Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicated that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Nutrición y alcoholismo crónico Nutrition and chronic alcohol abuse

    OpenAIRE

    R. Moreno Otero; Cortés, J. R.

    2008-01-01

    Muchos pacientes con etilismo crónico presentan un cuadro clínico de malnutrición, ya sea porque reducen la ingestión habitual de nutrientes esenciales o porque el alcohol impide la adecuada digestión y absorción de los distintos principios inmediatos, vitaminas y minerales. Un ejemplo común es el déficit de vitamina A en estos enfermos. Además, los propios procesos metabólicos del etanol (vía de la ADH y sistema MEOS) generan productos intermediarios tóxicos (acetaldehído, radicales libres) ...

  4. Effects of acamprosate on attentional set-shifting and cellular function in the prefrontal cortex of chronic alcohol-exposed mice

    Science.gov (United States)

    Hu, Wei

    Background: The medial prefrontal cortex (mPFC) inhibits impulsive and compulsive behaviors that characterize drug abuse and dependence. Acamprosate is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Whether acamprosate can modulate executive functions that are impaired by chronic ethanol exposure is unknown. Here we explored the effects of acamprosate on an attentional set-shifting task, and tested whether these behavioral effects are correlated with modulation of glutamatergic synaptic transmission and intrinsic excitability of mPFC neurons. Methods: We induced alcohol dependence in mice via chronic intermittent ethanol (CIE) exposure in vapor chambers and measured changes in alcohol consumption in a limited access 2-bottle choice paradigm. Impairments of executive function were assessed in an attentional set-shifting task. Acamprosate was applied subchronically for 2 days during withdrawal before the final behavioral test. Alcohol-induced changes in cellular function of layer 5/6 pyramidal neurons, and the potential modulation of these changes by acamprosate, were measured using patch clamp recordings in brain slices. Results: Chronic ethanol exposure impaired cognitive flexibility in the attentional set-shifting task. Acamprosate improved overall performance and reduced perseveration. Recordings of mPFC neurons showed that chronic ethanol exposure increased use-dependent presynaptic transmitter release and enhanced postsynaptic N-methyl-D-aspartate receptor (NMDAR) function. Moreover, CIE-treatment lowered input resistance, and decreased the threshold and the afterhyperpolarization (AHP) of action potentials, suggesting chronic ethanol exposure also impacted membrane excitability of mPFC neurons. However, acamprosate treatment did not reverse these ethanol-induced changes cellular function. Conclusion: Acamprosate improved attentional control of ethanol exposed animals

  5. IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Teige, Ingrid; Treschow, Alexandra; Teige, Anna

    2003-01-01

    Since the basic mechanisms behind the beneficial effects of IFN-beta in multiple sclerosis (MS) patients are still obscure, here we have investigated the effects of IFN-beta gene disruption on the commonly used animal model for MS, experimental autoimmune encephalomyelitis (EAE). We show that IFN......-beta knockout (KO) mice are more susceptible to EAE than their wild-type (wt) littermates; they develop more severe and chronic neurological symptoms with more extensive CNS inflammation and demyelination. However, there was no discrepancy observed between wt and KO mice regarding the capacity of T cells...... to proliferate or produce IFN-gamma in response to recall Ag. Consequently, we addressed the effect of IFN-beta on encephalitogenic T cell development and the disease initiation phase by passive transfer of autoreactive T cells from KO or wt littermates to both groups of mice. Interestingly, IFN-beta KO mice...

  6. INTEGRAL ESTIMATION OF OXIDATIVE STATUS IN PATIENTS WITH ACUTE TOXIC HEPATITIS AND CHRONIC ALCOHOLIC LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    A. Y. Shchupak

    2016-01-01

    Full Text Available BACKGROUND Acute toxic hepatitis associated with acute poisoning with alcohol-containing disinfectants remains a medical and social problem.MATERIAL AND METHODS With an aid of chemiluminescence, we performed the integrated assessment of the oxidative status in the blood serum and homogenized liver biopsy tissue of 62 patients with the diagnosis «severe acute toxic hepatitis associated with the use of alcohol-containing disinfectants».RESULTS The research showed that at the onset of a disease, patients with acute toxic hepatitis had an expressed activation of free radical oxidation of the blood serum and biopsy tissue. This was indicated by almost double increase in the intensity of free radicals generation (Ssp. This signifi cantly increased production of peroxide (Sind-1 and hydroxyl radicals (Slum — 2.5 and 1.86 times, respectively; also, it increased concentration of lipid hydroperoxides (h almost three times, evidencing activation of the initial stage of lipid peroxidation There was no statistically signifi cant fall of figures indicating the liver parenchymal oxidative status 30 days after the admission. The same situation was observed 6 months after the beginning of the study.CONCLUSION Analyzing chemiluminescence scans of blood serums up to 30 days from admission, it is possible to conclude indirectly on a condition of the oxidative status in a liver parenchyma of patients.

  7. Estimating uncertainty of alcohol-attributable fractions for infectious and chronic diseases

    Directory of Open Access Journals (Sweden)

    Frick Hannah

    2011-04-01

    Full Text Available Abstract Background Alcohol is a major risk factor for burden of disease and injuries globally. This paper presents a systematic method to compute the 95% confidence intervals of alcohol-attributable fractions (AAFs with exposure and risk relations stemming from different sources. Methods The computation was based on previous work done on modelling drinking prevalence using the gamma distribution and the inherent properties of this distribution. The Monte Carlo approach was applied to derive the variance for each AAF by generating random sets of all the parameters. A large number of random samples were thus created for each AAF to estimate variances. The derivation of the distributions of the different parameters is presented as well as sensitivity analyses which give an estimation of the number of samples required to determine the variance with predetermined precision, and to determine which parameter had the most impact on the variance of the AAFs. Results The analysis of the five Asian regions showed that 150 000 samples gave a sufficiently accurate estimation of the 95% confidence intervals for each disease. The relative risk functions accounted for most of the variance in the majority of cases. Conclusions Within reasonable computation time, the method yielded very accurate values for variances of AAFs.

  8. Chronic stress moderates the impact of social exclusion on pain tolerance: an experimental investigation.

    Science.gov (United States)

    Pieritz, Karoline; Schäfer, Sarina J; Strahler, Jana; Rief, Winfried; Euteneuer, Frank

    2017-01-01

    Experiences of social pain due to social exclusion may be processed in similar neural systems that process experiences of physical pain. The present study aimed to extend the findings on social exclusion and pain by examining the impact of social exclusion on an affective (ie, heat pain tolerance) and a sensory component of pain (ie, heat pain intensity). Whether a potential effect may be moderated by chronic life stress, social status, or social sup-port was further examined. A community-based sample of 59 women was studied. Social exclusion and inclusion were experimentally manipulated by using a virtual ball-tossing game called Cyberball in which participants were randomly assigned to either being excluded or being included by two other virtual players. Heat pain tolerance and intensity were assessed before and after the game. Potential psychosocial moderators were assessed via a questionnaire. The main finding of this study is that chronic stress moderates the impact of social exclusion on pain tolerance (psocially excluded participants showed a lower heat pain tolerance than participants who were socially included. Contrary to the authors' hypothesis, pain sensitivity was increased in socially included participants compared with socially excluded participants after the game (psocial exclusion.

  9. Mitral subvalvular plasty for chronic ischemic mitral regurgitation: a preliminary experimental model.

    Science.gov (United States)

    Evtushenko, Alexey V; Evtushenko, Vladimir V; Petlin, Konstantin A; Vaizov, Valery Kh; Petlin, Alexander V; Vassileva, Christina M

    2013-07-01

    Restrictive annuloplasty remains the most widespread technique for the correction of chronic ischemic mitral regurgitation (IMR). However, this technique only partially corrects the underlying pathophysiology and does not address the restricted leaflet motions during systole that result from progressive left ventricular (LV) remodeling. A novel experimental model of IMR was developed using an isolated pig heart placed on a hydrodynamic test-stand. A T-shaped LV patch was sutured onto the posterior wall of the left ventricle to simulate LV dilatation secondary to post-MI remodeling. Using this model, a novel technique of subvalvular mitral valvuloplasty was described that reduces the distance between the posterior mitral annulus and the papillary muscle base and appears to be effective in eliminating IMR. Pledgetted 2-0 non-absorbable sutures were placed at the base of one papillary muscle, then through the other papillary muscle and then brought to the posterior mitral annulus. The same sequence was repeated in the other direction. A specific formula was then used to calculate the length of the subvalvular support prior to suture tying. Subvalvular support of the mitral apparatus in chronic IMR can be achieved using this simple method, which appears to be effective in eliminating IMR. Further data relating to the use of this technique in the clinical setting as an adjunct to mitral annuloplasty are forthcoming.

  10. Treatment of Essential Tremor with Long-chain Alcohols: Still Experimental or Ready for Prime Time?

    Directory of Open Access Journals (Sweden)

    Dietrich Haubenberger

    2011-08-01

    Full Text Available Aim: To review current literature on long‐chain alcohols and their derivatives as novel pharmacotherapy for the treatment of essential tremor (ET. Background: Currently available and recommended pharmacotherapies for ET are often limited by suboptimal treatment effects, frequent adverse effects, and drug interactions. While ethanol is reported to profoundly decrease tremor severity in the majority of patients with ET, preclinical experience suggests that long‐chain alcohols such as 1‐octanol might lead to a comparable tremor reduction without ethanol’s typical side effects of sedation and intoxication. Here, we review the literature on the first clinical trials on 1‐octanol and its metabolite octanoic acid (OA for the treatment of ET.Methods: The literature on preclinical and clinical trials on long‐chain alcohols as well as OA was reviewed and summarized, and an outlook given on next phases of development.Discussion: 1‐octanol was demonstrated to be safe and effective in a double‐blind, placebo‐controlled low‐dose trial, and open‐label data showed excellent tolerability and dose‐dependent efficacy up to 128 mg/kg. Despite 1‐octanol’s efficacy, its future viability as an effective therapy is limited by its pharmacological properties that require large volumes to be orally administered. Pharmacokinetic data indicate that OA is the active metabolite of 1‐octanol. Preclinical efficacy data for OA are positive, and human pilot data demonstrated excellent safety as well as efficacy in secondary outcome measures of tremor amplitudes. OA also has more favorable pharmacological properties for drug delivery; hence, OA may be worth developing as a pharmaceutical.

  11. [Chronobiologic aspect of the mechanism of action of lithium salts in experimental alcoholism].

    Science.gov (United States)

    Iavorskiĭ, A N; Liubimov, B I

    1978-08-01

    Ethanol, used for 2 months in a 5% solution, disorganized the circadian cycle of the hystophysiologic activity of the rat epiphysis. During prolonged (course) administration in the doses close to those used at the clinic lithium chloride normalized the mentioned changes and also prevented their development in case of joint two-months use of ethanol and lithium salt. This effect of the drug correlates with the inhibition or prevention of the ethanol preference development observed under these perimental conditions. A possible interrelationship between the discovered capacity of lithium salt to normalize the chronobiological derangements of the epiphysis and clinical efficacy of these salts in alcoholism and other affective periodical disorders is discussed.

  12. A survey of the current clinical practice of psychiatrists and accident and emergency specialists in the United Kingdom concerning vitamin supplementation for chronic alcohol misusers.

    Science.gov (United States)

    Hope, L C; Cook, C C; Thomson, A D

    1999-01-01

    Although it is well known that B-vitamin deficiencies directly affecting the brain are common in alcohol misuse, no concise guidelines on the use of vitamin supplements in alcohol misusers currently exist in the UK. The purpose of this study was to assess current practice and opinion among UK physicians. Questionnaires were completed by a total of 427 physicians comprising Accident and Emergency (A&E) specialists and psychiatrists, with a response rate of 25%. The main findings were that vitamin deficiency was perceived as being uncommon amongst alcohol misusers (Wernicke-Korsakoff syndrome in chronic alcohol misusers and parenteral therapy in patients with signs of Wernicke-Korsakoff syndrome. Whilst only just over half the A&E specialists expressed a preference, most favoured parenteral therapy in both cases. Most respondents did not currently have a unit policy/protocol on the management of vitamin supplementation in chronic alcohol misusers. Overall, the findings suggest that there is wide variation in current practice and highlight the need for guidelines in this area.

  13. Simultaneous determination of blood glucose and isoleucine levels in rats after chronic alcohol exposure by microwave-assisted derivatization and isotope dilution gas chromatography/mass spectrometry.

    Science.gov (United States)

    Xue, Ruyi; Zhang, Si; Deng, Chunhui; Dong, Ling; Liu, Taotao; Wang, Jiyao; Wu, Hongyi; Gu, Jianxin; Shen, Xizhong

    2008-01-01

    Blood glucose and isoleucine are two biomarkers of chronic alcohol exposure. Simultaneous determination of blood glucose and isoleucine levels helps to illuminate the influence of alcohol on the metabolism of glucose and amino acids. The most accurate method for the detection of serum glucose is isotope dilution gas chromatography/mass spectrometry (ID GC/MS). In this study, a rapid, simple and sensitive technique was developed for the quantitative analysis of glucose and isoleucine in rats after chronic alcohol exposure by microwave-assisted derivatization (MAD) and ID GC/MS. Serum glucose and isoleucine were rapidly derivatized by N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) with microwave irradiation, and the trimethylsilyl derivatives were analyzed by GC/MS. This technique was used to demonstrate that pyrroloquinoline quinone (PQQ), a non-covalently bound prosthetic group in some quinoproteins involved in the metabolism of some sugar or alcohol, could reverse alcohol exposure induced glucose elevation. On the other hand, it did not affect the metabolism of isoleucine whose level was elevated along with serum glucose. The combination of MAD and ID GC/MS has been shown to be an accurate, rapid, simple and sensitive method for the quantification of glucose and isoleucine in serum samples. Copyright (c) 2007 John Wiley & Sons, Ltd.

  14. Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence

    Energy Technology Data Exchange (ETDEWEB)

    Xu, R.; Duan, S.R.; Zhao, J.W.; Wang, C.Y. [Neurology Ward of Internal Medicine, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province (China)

    2015-06-23

    Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

  15. Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence.

    Science.gov (United States)

    Xu, R; Duan, S R; Zhao, J W; Wang, C Y

    2015-08-01

    Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

  16. The action of demineralized bovine bone matrix on bone neoformation in rats submitted to experimental alcoholism

    Directory of Open Access Journals (Sweden)

    R.L. Buchaim

    2013-06-01

    Full Text Available The objective of this study was to evaluate whether demineralized bovine bone (Gen-ox® alters bone neoformation in rats submitted to alcoholism. Forty male rats were separated into two groups of 20 rats and distributed as follows: Group E1, which received 25% ethanol and a surgical cavity filled only by a blood clot, and Group E2, which received 25% ethanol and a surgical cavity filled with Gen-ox®. The animals were euthanized at 10, 20, 40 and 60 days after surgery and necropsy was performed. The histomorphological and histometric analyses of the area of connective tissue and bone neoformation showed that the reorganization of the bone marrow and full repair of the surgical cavity in Group E1 occurred more quickly than in Group E2. It was also noted that in the final period the animals in Group E2 showed areas of connective tissue and thick bone trabeculae around the particles of the implant. It can be concluded that the use of Gen-ox® delayed the process of bone repair in alcoholic rats, although it can be used as filling material because it shows osteoconductive activity, as evidenced by bone tissue formation around the graft particles.

  17. Women and Alcohol

    Science.gov (United States)

    ... the risk of many chronic diseases, moderate alcohol consumption is up to one drink per day for women and up to two ... regularly misuse alcohol are more likely to develop alcoholic hepatitis, a serious acute illness, than men who drink the same amount of alcohol. This pattern of ...

  18. Environmental properties of long-chain alcohols. Structure-activity Relationship for Chronic Aquatic Toxicity

    DEFF Research Database (Denmark)

    Schaefers, Christoph; Sanderson, Hans; Boshof, Udo

    2009-01-01

    of toxicity to C15 alcohol were not in line with lower chain lengths due to the lack of toxicity below the level of water solubility. When omitting C15, the slope of most (Q)SARs approach -1, being consistent with the expectation of a non-polar narcotic mode of action. Further testing at higher chain lengths...... substances and the need to test as close as possible to their water solubility limits. Test concentrations were determined by GC-MS before and after test solution renewal. Whereas apparent toxicity based on survival and reproduction increased with increasing C-chain lengths up to C14, observations...... is not sensible due to progressively lower solubility, at remaining biodegradability. Effects on mortality and reproduction are not expected below the level of water solubility. © 2008 Elsevier Inc. All rights reserved....

  19. Experimental effect of positive urgency on negative outcomes from risk taking and on increased alcohol consumption

    OpenAIRE

    Cyders, Melissa A.; Zapolski, Tamika C. B.; Combs, Jessica L.; Settles, Regan Fried; Fillmore, Mark T.; Smith, Gregory T.

    2010-01-01

    The current pair of experimental studies sought to further validate the role of positive urgency (acting rashly when in an extreme positive emotional state) as a risk factor for impulsive and maladaptive behavior. Previous research has supported the use of emotion-based dispositions to rash action in predicting a wide range of maladaptive acts. However, that research was conducted in the field and relied on self-reported behavior, thus lacking tight experimental controls and direct observatio...

  20. Cerebellar white matter inflammation and demyelination in chronic relapsing experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Wanscher, B.; Sørensen, P. S.; Juhler, M.

    1993-01-01

    Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology......Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology...

  1. Identification and experimental characterization of an extremophilic brine pool alcohol dehydrogenase from single amplified genomes

    KAUST Repository

    Grötzinger, Stefan W.

    2017-11-30

    Because only 0.01% of prokaryotic genospecies can be cultured and in situ observations are often impracticable, culture-independent methods are required to understand microbial life and harness potential applications of microbes. Here, we report a methodology for the production of proteins with desired functions based on single amplified genomes (SAGs) from unculturable species. We use this method to resurrect an alcohol dehydrogenase (ADH/D1) from an uncharacterized halo-thermophilic archaeon collected from a brine pool at the bottom of the Red Sea. Our crystal structure of 5,6-dihydroxy NADPH-bound ADH/D1 combined with biochemical analyses reveal the molecular features of its halo-thermophily, its unique habitat adaptations, and its possible reaction mechanism for atypical oxygen activation. Our strategy offers a general guide for using SAGs as a source for scientific and industrial investigations of ‘microbial dark matter’.

  2. Thermodynamic study of sesamol, piperonyl alcohol, piperonylic acid and homopiperonylic acid: a combined experimental and theoretical investigation.

    Science.gov (United States)

    Matos, M Agostinha R; Monte, Manuel J S; Sousa, Clara C S; Almeida, Ana R R P; Morais, Victor M F

    2004-03-21

    The standard (p(o)= 0.1 MPa) molar energies of combustion in oxygen, at T= 298.15 K, of four 1,3-benzodioxole derivatives (sesamol, piperonyl alcohol, piperonylic acid and homopiperonylic acid) were measured by static bomb calorimetry. The values of the standard molar enthalpies of sublimation, at T= 298.15 K, were derived from vapour pressure-temperature measurements using the Knudsen effusion technique. Combining these results the standard molar enthalpies of formation of the compounds, in the gas phase, at T= 298.15 K, have been calculated: sesamol (-325.7 +/- 1.9) kJ mol(-1); piperonyl alcohol (-329.0 +/- 2.0) kJ mol(-1); piperonylic acid (-528.9 +/- 2.6) kJ mol(-1) and homopiperonylic acid (-544.5 +/- 2.9) kJ mol(-1). The most stable geometries of all the compounds were obtained using the density functional theory with the B3LYP functional and two basis sets: 6-31G** and 6-311G**. The nonplanarity of the molecules was analyzed in terms of the anomeric effect, which is believed to arise from the interaction between a nonbonded oxygen p orbital and the empty orbital sigma*(CO) involving the other oxygen atom. Calculations were performed to obtain estimates of the enthalpies of formation of all the benzodioxoles using appropriate isodesmic reactions. There is a perfect agreement between theoretical and experimental results.

  3. The interaction of chronic restraint stress and voluntary alcohol intake: effects on spatial memory in male rats.

    Science.gov (United States)

    Gomez, Juan L; Lewis, Michael J; Luine, Victoria N

    2012-08-01

    Alcohol consumption and exposure to stressful life events activate similar neural pathways and thus result in several comparable physiological and behavioral effects. Alcoholics in treatment claim that life stressors are the leading cause of continued drinking or relapse. However, few studies have investigated the interactive effects of stress and alcohol on cognitive behavior. The effects of restraint stress, alcohol, and stress in combination with alcohol were examined on a spatial memory test, the object placement (OP) task. In addition, intake levels were measured to determine if stress altered general consumption of alcohol. Male Sprague-Dawley rats were assigned to one of four conditions: no alcohol/no stress control (CON), stress alone (STR), alcohol alone (ALC), and STR+alcohol (STR+ALC). Following each restraint stress bout, the STR+ALC and the ALC groups were given access to 8% alcohol for 1h using the two-bottle choice limited access paradigm. As predicted, the STR+ALC group significantly increased alcohol consumption, while the ALC group had consistent drinking over the 10-day treatment. On the OP task, STR and ALC groups performed at chance levels, whereas the CON and STR+ALC groups significantly discriminated between objects in the new and old locations. These data show that stress increases alcohol intake and the intake of alcohol is associated with reduction of the stress-induced impairment of spatial memory. The data have important implications for the development of alcohol abuse and its treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Alcoholism and Alcohol Abuse

    Science.gov (United States)

    ... causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that ... more alcohol to feel the same effect With alcohol abuse, you are not physically dependent, but you still ...

  5. Elucidation of possible mechanism of analgesic action of Valeriana wallichii DC chemotype (patchouli alcohol) in experimental animal models.

    Science.gov (United States)

    Sah, Sangeeta Pilkhwal; Mathela, Chandra S; Chopra, Kanwaljit

    2010-03-01

    Valeriana wallichii (Family Valerianaceae), popularly named as Indian valerian, exists as three chemotypes. Aim of the study was to evaluate the effect of V. wallichii chemotype (patchouli alcohol) extract (DCME) and essential oil (VPAEO) on experimental models of nociception and to elucidate its possible mechanism of action. Analgesic effect was evaluated using acetic acid induced writhing and tail flick model. DCME and VPAEO (40 and 80 mg/kg, p.o.) significantly inhibited the number of writhings as compared to vehicle treated group. None of the doses of DCME and VPAEO exhibited any effect in tail flick model suggesting only peripheral analgesic activity. When studied for mechanism of action in acetic acid induced writhing, subeffective dose of essential oil significantly potentiated the effect of aspirin while no potentiation was seen in case of extract. These data suggest that essential oil VPAEO exerted peripheral analgesic via inhibition of prostaglandin synthesis.

  6. Epidemiology of alcohol-associated cancers.

    Science.gov (United States)

    Brown, Linda Morris

    2005-04-01

    Alcohol, especially in combination with smoking, is a well-established risk factor for cancers of the oral cavity and pharynx, esophagus, and larynx, with 25% to 80% of these cancers being attributable to alcohol. Rates of these cancers in the United States have been decreasing in recent years, possibly because of reductions in cigarette smoking and alcohol use. Chronic alcohol consumption has been linked with increased risk of liver cancer in epidemiologic studies. However, the rising rates of this cancer in the United States are most likely due to the increasing prevalence of chronic hepatitis B and C infections. Epidemiologic evidence has linked light to moderate intake of alcohol to cancers of the colorectum and female breast. These cancers are common in developed countries, so even small increases in risk can have important public health implications. Although results of most epidemiologic studies have provided little or no support for a causal relation between light and moderate alcohol use and risk of pancreatic cancer, a possible role of heavy alcohol consumption cannot be ruled out. Further studies of these cancers are needed to clarify the role of type of alcoholic beverage, the role of alcohol concentration, and the dose-response curve at low concentrations of alcohol. Future research also should be designed to promote the use of uniform ways to report alcohol intake and uniform measures for analysis, to include the investigation of alcohol-associated cancer risks in U.S. minority populations, to enhance experimental work to better understand the underlying mechanisms through which alcohol promotes carcinogenesis, and to develop preventive strategies.

  7. Alcohol consumption, physical activity, and chronic disease risk factors: a population-based cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Djoussé Luc

    2006-05-01

    Full Text Available Abstract Background Whether the association of alcohol consumption and cardiovascular disease is the product of confounding and the degree to which this concern applies to other behaviors are unclear. Methods Using the 2003 Behavioral Risk Factor Surveillance System, a population-based telephone survey of adults in the US, we compared chronic disease risk factors between 123,359 abstainers and 126,674 moderate drinkers, defined as intake of ≤ 2 drinks per day among men and ≤ 1 drink per day among women, using age- and sex- and multivariable-adjusted models. We also compared sedentary and active individuals, defined as moderate physical activity ≥ 30 minutes per day for ≥ 5 days per week, or vigorous activity for ≥ 20 minutes per day on ≥ 3 days. Results Chronic disease risk factors and features of unhealthy lifestyle were generally more prevalent among abstainers than drinkers in age- and sex-adjusted analyses, but these differences were generally attenuated or eliminated by additional adjustment for race and education. For low fruit and vegetable intake, divorced marital status, and absence of a personal physician, adjustment for race and education reversed initially positive age- and sex-adjusted associations with abstention. Comparison of sedentary and active individuals produced similar findings, with generally lower levels of risk factors among more physical active individuals. Conclusion The differences between abstainers and drinkers are attenuated after adjustment for limited sociodemographic features, and sedentary and active individuals share a similar pattern. Although observational studies of both factors may be susceptible to uncontrolled confounding, our results provide no evidence that moderate drinking is unique in this regard. Ultimately, randomized trials of all such lifestyle factors will be needed to answer these questions definitively.

  8. Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in treatment-naïve patients with chronic hepatitis B infection

    Directory of Open Access Journals (Sweden)

    Won Gil Chung

    2012-06-01

    Full Text Available Background/AimsThe aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV therapy in chronic hepatitis B (CHB patients.MethodsThe medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI values and Alcohol Use Disorders Identification Test (AUDIT scores were obtained at 6 months after the initiation of ETV (0.5 mg daily treatment.ResultsA BMI of 25 kg/m2 or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3% were obese and 17 (19.3% were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT normalization, and hepatitis B virus (HBV-DNA negativity (<300 copies/mL at 3, 6, and 12 months of treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not differ significantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was significantly lower among hazardous alcohol users (91.5% vs. 70.6%; P=0.033.ConclusionsObesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was significantly lower among the hazardous alcohol users.

  9. Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in treatment-naïve patients with chronic hepatitis B infection.

    Science.gov (United States)

    Chung, Won Gil; Kim, Hong Joo; Choe, Young Gil; Seok, Hyo Sun; Chon, Chang Wook; Cho, Yong Kyun; Kim, Byung Ik; Koh, Young Yool

    2012-06-01

    The aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV) therapy in chronic hepatitis B (CHB) patients. The medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI) values and Alcohol Use Disorders Identification Test (AUDIT) scores were obtained at 6 months after the initiation of ETV (0.5 mg daily) treatment. A BMI of 25 kg/m(2) or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3%) were obese and 17 (19.3%) were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT) normalization, and hepatitis B virus (HBV)-DNA negativity (treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not differ significantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was significantly lower among hazardous alcohol users (91.5% vs. 70.6%; P=0.033). Obesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was significantly lower among the hazardous alcohol users.

  10. Experimental liver fibrosis induced in rats receiving high doses of alcohol and alternating between regular and vitamin-depleted diets.

    Science.gov (United States)

    Hirano, H; Hirano, T; Hirata, K; Tamura, M; Yamaura, T; Hamada, T

    1996-07-15

    Liver fibrosis was induced in rats by simulating human alcoholic eating and drinking patterns. Alcohol addiction was established by gradually increasing the ethanol concentration in the drinking water; salts were added at the terminal stage. The hepatocytes of rats receiving alcohol concentrations exceeding 50% (v/v) (similar to vodka) exhibited alcoholic hyaline (Mallory bodies). Alcoholic liver fibrosis was induced by alternating between regular and autoclaved (vitamin-depleted) diets, simulating the irregular eating habits of human alcoholics. In the livers of rats receiving 70% (v/v) ethanol (comparable to absinthe) with 25% saline and fed the alternating diets, pericellular fibrosis was induced. No significant difference in calorie intake between control and alcohol rats was detected except when rats underwent drinking bouts (heavy drinking phase). This indicates that neither a high-fat diet nor a choline-depleted diet is necessary to induce the alcoholic fibrosis seen in human alcoholics.

  11. Stereotypic information about drinkers and students' observed alcohol intake: an experimental study on prototype-behavior relations in males and females in a naturalistic drinking context.

    Science.gov (United States)

    Teunissen, Hanneke A; Spijkerman, Renske; Larsen, Helle; Kremer, Kirsten A; Kuntsche, Emmanuel; Gibbons, Frederick X; Scholte, Ron H J; Engels, Rutger C M E

    2012-10-01

    Cross-sectional and longitudinal research has shown that favorable drinker prototypes (i.e., perceptions about the typical drinker) are related to higher levels of alcohol consumption in adolescents and college students. So far, few studies have experimentally tested the causality of this relationship and it is not clear what type of manipulation affects drinker prototypes and drinking levels. In an experimental 1-factor design with two levels, we tested the short-term effects of exposing students to either positive or negative stereotypic information about drinkers on their drinker prototypes and actual drinking behaviors. We exposed 192 male and female college students to positive drinker prototype information (drinkers in general were presented as being attractive, sociable and successful), or to negative information (unattractive, unsociable and unsuccessful). Subsequently, participants' levels of alcohol consumption were observed unobtrusively while they were interacting with peers in a naturalistic drinking context, namely a bar lab. Participants exposed to positive stereotypic information about drinkers reported more favorable drinker prototypes than participants exposed to negative stereotypic information. Multilevel analyses revealed that men's subsequent alcohol consumption in the bar lab was higher in the positive prototype condition than in the negative prototype condition. For women, no prototype effects on alcohol use were found. These findings underline that drinker prototypes affect actual alcohol use in men and suggest that changing perceptions of drinkers may be a useful tool in alcohol prevention programs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. [Effect of post-treatment with dry extract from vicia truncatula on NADPH-GSH dependent system of rat liver during chronic alcohol intoxication].

    Science.gov (United States)

    Dorkina, E G

    2010-04-01

    Experiments on white female rats showed that chronic ethanol consumption leads to activation of the NADPH - GSH dependent system of the liver, which provides protection against ethanol-induced oxidative stress. Post-treatment administration of dry extract from Vicia truncatula Fish ex Bieb. (300 mg/kg body weight) on the background of 40% ethanol increased this adaptive reaction without depletion in the system, in contrast to what was observed in rats treated with carsil. These results suggest a significant hepatoprotective effect of the dry extract during the chronic alcohol-induced injury of the liver.

  13. Moderate alcohol consumption is associated with lower chronic disease burden expressed in disability-adjusted life years: a prospective cohort study.

    Science.gov (United States)

    Beulens, Joline W J; Fransen, Heidi P; Struijk, Ellen A; Boer, Jolanda M A; de Wit, G Ardine; Onland-Moret, N Charlotte; Hoekstra, Jeljer; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; May, Anne M

    2017-04-01

    The relation of alcohol consumption with disease burden remains debated partly due to opposite associations with cardiovascular disease (CVD) and cancer. The relation of alcohol consumption with disease burden expressed in disability-adjusted life years (DALYs) summarizes opposing associations of alcohol consumption on chronic diseases. This study aimed to investigate the association of alcohol consumption with chronic disease burden expressed in DALYs based on individual-participant data. The study was a prospective study among 33,066 men and women from the EPIC-NL cohort. At baseline, alcohol consumption was assessed with a validated food-frequency questionnaire. Participants were followed for occurrence of and mortality from chronic diseases and DALYs were calculated. After 12.4 years follow-up, 6647 disease incidences and 1482 deaths were documented, resulting in 68,225 healthy years of life lost (6225 DALYs). Moderate drinkers (women 5-14.9 g/day, men 5-29.9 g/day) had a lower chronic disease burden (mean DALYs -0.27; 95% CI -0.43; -0.11) than light drinkers (0-4.9 g/day), driven by a lower disease burden due to CVD (-0.18: -0.29; -0.06) but not cancer (-0.05: -0.16; 0.06). The associations were most pronounced among older participants (≥50 years; -0.32; -0.53; -0.10) and not observed among younger women (-0.08; -0.43; 0.35), albeit non-significant (pinteraction > 0.14). Substantial drinking (women 15-29.9 g/day, men 30-59.9 g/day) compared to light drinking was not associated with chronic disease burden. Our results show that moderate compared to light alcohol consumption was associated with living approximately 3 months longer in good health. These results were mainly observed among older participants and not seen among younger women.

  14. The Effects of Music Genre on Young People's Alcohol Consumption: An Experimental Observational Study

    NARCIS (Netherlands)

    Engels, R.C.M.E.; Poelen, E.A.P.; Spijkerman, R.; Bogt, T.F.M. ter

    2012-01-01

    he aim of this study was to test whether exposure to specific music genres in a social drinking setting leads to differences in drinking levels. An observational experimental design was used in which we invited peer groups of young adults into a bar lab, a lab which is furnished like an ordinary,

  15. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    1999-01-01

    Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

  16. Does swimming exercise affect experimental chronic kidney disease in rats treated with gum acacia?

    Directory of Open Access Journals (Sweden)

    Badreldin H Ali

    Full Text Available Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD. Similar benefits have also been ascribed to the dietary supplement gum acacia (GA. Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE on adenine-induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w to induce CKD, GA in the drinking water (15% w/v, or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments, during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation.

  17. Alcohol and bone.

    Science.gov (United States)

    Mikosch, Peter

    2014-01-01

    Alcohol is widely consumed across the world in different cultural and social settings. Types of alcohol consumption differ between (a) light, only occasional consumption, (b) heavy chronic alcohol consumption, and (c) binge drinking as seen as a new pattern of alcohol consumption among teenagers and young adults. Heavy alcohol consumption is detrimental to many organs and tissues, including bones. Osteoporosis is regularly mentioned as a secondary consequence of alcoholism, and chronic alcohol abuse is established as an independent risk factor for osteoporosis. The review will present the different mechanisms and effects of alcohol intake on bone mass, bone metabolism, and bone strength, including alcoholism-related "life-style factors" such as malnutrition, lack of exercise, and hormonal changes as additional causative factors, which also contribute to the development of osteoporosis due to alcohol abuse.

  18. Behavioral, metabolic, and immune consequences of chronic alcohol or cannabinoids on HIV/AIDs: Studies in the Non-Human Primate SIV model

    Science.gov (United States)

    Molina, Patricia E.; Amedee, Angela M.; Winsauer, Peter; Nelson, Steve; Bagby, Gregory; Simon, Liz

    2015-01-01

    HIV-associated mortality has been significantly reduced with antiretroviral therapy (ART), and HIV infection has become a chronic disease that frequently coexists with many disorders, including substance abuse (Azar et al. 2010; Phillips et al. 2001). Alcohol and drugs of abuse may modify host-pathogen interactions at various levels including behavioral, metabolic, and immune consequences of HIV infection, as well as the ability of the virus to integrate into the genome and replicate in host cells. Identifying mechanisms responsible for these interactions is complicated by many factors, such as the tissue specific responses to viral infection, multiple cellular mechanisms involved in inflammatory responses, neuroendocrine and localized responses to infection, and kinetics of viral replication. An integrated physiological analysis of the biomedical consequences of chronic alcohol and drug use or abuse on disease progression is possible using rhesus macaques infected with simian immunodeficiency virus (SIV), a relevant model of HIV infection. This review will provide an overview of the data gathered using this model to show that chronic administration of two of the most commonly abused substances, alcohol and cannabinoids (Δ9-Tetrahydrocannabinol; THC), affect host-pathogen interactions. PMID:25795088

  19. Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection

    Directory of Open Access Journals (Sweden)

    S. R. Alam

    2015-01-01

    Full Text Available Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO- enhanced magnetic resonance imaging (MRI can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2∗-weighted protocols. R2∗ values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2∗ values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36 versus 0.96 (0.92 to 1.04, P<0.01. R2∗ values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51 compared to native kidney (2.91 (1.11 to 6.46 P<0.05. Increased R2∗ signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.

  20. Anti-melanin-concentrating hormone treatment attenuates chronic experimental colitis and fibrosis.

    Science.gov (United States)

    Ziogas, Dimitrios C; Gras-Miralles, Beatriz; Mustafa, Sarah; Geiger, Brenda M; Najarian, Robert M; Nagel, Jutta M; Flier, Sarah N; Popov, Yury; Tseng, Yu-Hua; Kokkotou, Efi

    2013-05-15

    Fibrosis represents a major complication of several chronic diseases, including inflammatory bowel disease (IBD). Treatment of IBD remains a clinical challenge despite several recent therapeutic advances. Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide shown to regulate appetite and energy balance. However, accumulating evidence suggests that MCH has additional biological effects, including modulation of inflammation. In the present study, we examined the efficacy of an MCH-blocking antibody in treating established, dextran sodium sulfate-induced experimental colitis. Histological and molecular analysis of mouse tissues revealed that mice receiving anti-MCH had accelerated mucosal restitution and lower colonic expression of several proinflammatory cytokines, as well as fibrogenic genes, including COL1A1. In parallel, they spared collagen deposits seen in the untreated mice, suggesting attenuated fibrosis. These findings raised the possibility of perhaps direct effects of MCH on myofibroblasts. Indeed, in biopsies from patients with IBD, we demonstrate expression of the MCH receptor MCHR1 in α-smooth muscle actin(+) subepithelial cells. CCD-18Co cells, a primary human colonic myofibroblast cell line, were also positive for MCHR1. In these cells, MCH acted as a profibrotic modulator by potentiating the effects of IGF-1 and TGF-β on proliferation and collagen production. Thus, by virtue of combined anti-inflammatory and anti-fibrotic effects, blocking MCH might represent a compelling approach for treating IBD.

  1. [Clinical study of non-alcoholic fatty liver disease and its combined the chronic HBV infection].

    Science.gov (United States)

    He, J; Zeng, Y L; Li, W; Guo, E E; Li, J L; Kang, Y; Shang, J

    2017-08-20

    Objective: to compared with clinical data between nonalcoholic fatty liver disease (NAFLD) and Chronic HBV infection with NAFLD, and to explore the relationship between HBV infection and hepatic steatosis. Methods: A total of 81 patients with clinical data in the Department of Infectious Diseases in Henan Provincial People's Hospital from June 2013 to June 2016 were enrolled and divided into NAFLD group and HBV combined NAFLD group.Comparison of The levels of liver function (ALT, AST, ALP, GGT), blood lipid (TC, TG, HDL, LDL), blood glucose (GLU), uric acid (UA), hepatic fibrosis (S) and inflammation (G) And hepatic steatosis (F), and to explore the relationship between HBV infection and hepatic steatosis. The independent samples t-test or Wilcoxon two -sample test was used for comparison of continuous data,and the chi-square test was used for comparison of categorical data. Multinomial Logistic regression was used to analyze The risk factors of hepatic steatosis, P HBV with NAFLD group. Baseline level comparison: ALT (t = -4.379, P HBV infection-related indicators, it is difficult to distinguish between NAFLD and NAFLD combined with HBV differences; HBV infection and hepatic steatosis have a certain relationship.

  2. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Xiang Li

    Full Text Available We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP tests. Additionally, compared with the chronic alcohol (1.0% treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5% generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  3. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Science.gov (United States)

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  4. Stereotypic information about drinkers and students' observed alcohol intake: An experimental study on prototype-behavior relations in males and females in a naturalistic drinking context

    NARCIS (Netherlands)

    Teunissen, H.A.; Spijkerman, R.; Larsen, H.; Kremer, K.A.; Kuntsche, E.N.; Gibbons, F.X.; Scholte, R.H.J.; Engels, R.C.M.E.

    2012-01-01

    Background: Cross-sectional and longitudinal research has shown that favorable drinker prototypes (i.e., perceptions about the typical drinker) are related to higher levels of alcohol consumption in adolescents and college students. So far, few studies have experimentally tested the causality of

  5. Stereotypic information about drinkers and students' observed alcohol intake: an experimental study on prototype-behavior relations in males and females in a naturalistic drinking context

    NARCIS (Netherlands)

    Teunissen, H.A.; Spijkerman, R.; Larsen, H.; Kremer, K.A.; Kuntsche, E.; Gibbons, F.X.; Scholte, R.H.J.; Engels, R.C.M.E.

    2012-01-01

    Background: Cross-sectional and longitudinal research has shown that favorable drinker prototypes (i.e., perceptions about the typical drinker) are related to higher levels of alcohol consumption in adolescents and college students. So far, few studies have experimentally tested the causality of

  6. Pain, alcohol use disorders and risky patterns of drinking among people with chronic non-cancer pain receiving long-term opioid therapy.

    Science.gov (United States)

    Larance, Briony; Campbell, Gabrielle; Peacock, Amy; Nielsen, Suzanne; Bruno, Raimondo; Hall, Wayne; Lintzeris, Nicholas; Cohen, Milton; Degenhardt, Louisa

    2016-05-01

    The utilisation of pharmaceutical opioids has increased internationally, and there is evidence of increasing risky alcohol consumption with ageing. This study examines the patterns and correlates of risky drinking among people with chronic non-cancer pain (CNCP) prescribed opioids, and the associations between alcohol consumption and pain. The Pain and Opioids IN Treatment cohort comprises 1514 people in Australia prescribed pharmaceutical opioids for CNCP. Participants reported lifetime, past year and past month alcohol use, as well as mental and physical health, other substance use, pain characteristics, and current opioid dose. Less than one-tenth of the sample were 'lifetime abstainers' (7%); 34% were 'former drinkers'; 34% were 'non-risky drinkers' (i.e., past 12 month use ≤4 standard drinks); 16% were 'occasional risky drinkers'; and 8% were 'regular risky drinkers' (i.e., ≥weekly use of >4 standard drinks). Males reported greater levels of alcohol use, and a third (33%) of the total sample reported a lifetime alcohol use disorder. Controlling for demographics, mental health, physical health and substance use disorder history, 'former drinkers' (cf. 'non-risky drinkers') reported higher pain severity and interference ratings, and lower pain coping. 'Occasional risky drinkers' and 'regular risky drinkers' (cf. 'non-risky drinkers') reported higher levels of pain interference. Among people with CNCP, those who abstained from alcohol or drank at risky levels reported poorer pain outcomes compared with moderate drinkers. Early identification and intervention for risky drinking among people is critical, particularly given the risks associated with co-administration of alcohol and opioids. Copyright © 2016. Published by Elsevier Ireland Ltd.

  7. Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration.

    Directory of Open Access Journals (Sweden)

    James Haorah

    Full Text Available Neuropathy and neurocognitive deficits are common among chronic alcohol users, which are believed to be associated with mitochondrial dysfunction in the brain. The specific type of brain mitochondrial respiratory chain complexes (mRCC that are adversely affected by alcohol abuse has not been studied. Thus, we examined the alterations of mRCC in freshly isolated mitochondria from mice brain that were pair-fed the ethanol (4% v/v and control liquid diets for 7-8 weeks. We observed that alcohol intake severely reduced the levels of complex I and V. A reduction in complex I was associated with a decrease in carnitine palmitoyltransferase 1 (cPT1 and cPT2 levels. The mitochondrial outer (cPT1 and inner (cPT2 membrane transporter enzymes are specialized in acylation of fatty acid from outer to inner membrane of mitochondria for ATP production. Thus, our results showed that alterations of cPT1 and cPT2 paralleled a decrease β-oxidation of palmitate and ATP production, suggesting that impairment of substrate entry step (complex I function can cause a negative impact on ATP production (complex V function. Disruption of cPT1/cPT2 was accompanied by an increase in cytochrome C leakage, while reduction of complex I and V paralleled a decrease in depolarization of mitochondrial membrane potential (ΔΨ, monitored by JC-1 fluorescence and ATP production in alcohol intake. We noted that acetyl-L-carnitine (ALC, a cofactor of cPT1 and cPT2 prevented the adverse effects of alcohol while coenzyme Q10 (CoQ10 was not very effective against alcohol insults. These results suggest that understanding the molecular, biochemical, and signaling mechanisms of the CNS mitochondrial β-oxidation such as ALC can mitigate alcohol related neurological disorders.

  8. Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism.

    Science.gov (United States)

    Qu, Chang; Yuan, Zhong-Wen; Yu, Xiu-Ting; Huang, Yan-Feng; Yang, Guang-Hua; Chen, Jian-Nan; Lai, Xiao-Ping; Su, Zi-Ren; Zeng, Hui-Fang; Xie, Ying; Zhang, Xiao-Jun

    2017-07-01

    Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to

  9. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Musso, Giovanni; Gambino, Roberto; Tabibian, James H; Ekstedt, Mattias; Kechagias, Stergios; Hamaguchi, Masahide; Hultcrantz, Rolf; Hagström, Hannes; Yoon, Seung Kew; Charatcharoenwitthaya, Phunchai; George, Jacob; Barrera, Francisco; Hafliðadóttir, Svanhildur; Björnsson, Einar Stefan; Armstrong, Matthew J; Hopkins, Laurence J; Gao, Xin; Francque, Sven; Verrijken, An; Yilmaz, Yusuf; Lindor, Keith D; Charlton, Michael; Haring, Robin; Lerch, Markus M; Rettig, Rainer; Völzke, Henry; Ryu, Seungho; Li, Guolin; Wong, Linda L; Machado, Mariana; Cortez-Pinto, Helena; Yasui, Kohichiroh; Cassader, Maurizio

    2014-07-01

    Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in

  10. Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats.

    Science.gov (United States)

    Yu, Jie; Yang, Xuesong; Luo, Ya; Yang, Xuefeng; Yang, Mengxue; Yang, Jin; Zhou, Jie; Gao, Feng; He, Liting; Xu, Jie

    2017-01-01

    Endocrine-disrupting chemical (EDC) has been thought to play a role in non-alcoholic fatty liver disease (NAFLD). However, the toxic effects of Nonylphenol (NP), an EDC, on non-alcoholic fatty liver disease have never been elaborated. This study aimed to investigate whether exposure to NP could induce NAFDL, a promoting effect of high-sucrose-high-fat diet (HSHFD) on the adverse effects caused by NP was evaluated. Fourth eight male rats were assigned to four groups and each group was treated with a specific testing sample: normal-diet (ND) control group (C-ND); normal diet plus NP (180mg/kg/day) group (NP-ND); high-sucrose-high-fat-diet control group (C-HSHFD); HSHFD plus NP (180mg/kg/day) group (NP-HSHFD). At the age of 80 day, sonogram presents diffusely increased hepatic echogenicity in the NP-HSHFD group. The oblique diameter of liver in the NP-HSHFD group was significantly bigger than that in both the C-ND and NP-ND groups. At the age of 90 day, exposure to NP-HSHFD and NP-ND caused a significant increase in NP concentration in liver as compared to the C-ND group. The rats in the groups treated with NP+ND, HSHFD and NP+HSHFD produced significant increases in the body weight, fat weight and FMI, respectively, when compared to the C-ND group. The liver weight and hepatosomatic indexes (HIS) of rats in the NP-HSHFD group are higher than those in the C-HSHFD group. Exposure to NP-HSHFD induced the increases in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) as compared to the C-ND group. Morphological examination of liver tissue from rats exposed to NP+HSHFD shown steatosis with marked accumulation of lipid droplets, hepatocellular ballooning degeneration and inflammatory cell infiltration. Chronic exposure to NP might induce NAFLD in male rats. The high-sucrose-high-fat diet accelerates and exacerbates the development of NAFLD caused by NP exposure.

  11. Combustion chemistry of alcohols: Experimental and modeled structure of a premixed 2-methylbutanol flame

    KAUST Repository

    Lucassen, Arnas

    2014-06-14

    This paper presents a detailed investigation of 2-methylbutanol combustion chemistry in low-pressure premixed flames. This chemistry is of particular interest to study because this compound is potentially a lignocellulosic-based, next-generation biofuel. The detailed chemical structure of a stoichiometric low-pressure (25 Torr) flame was determined using flame-sampling molecular-beam mass spectrometry. A total of 55 species were identified and subsequently quantitative mole fraction profiles as function of distance from the burner surface were determined. In an independent effort, a detailed flame chemistry model for 2-methylbutanol was assembled based on recent knowledge gained from combustion chemistry studies for butanol isomers ([Sarathy et al. Combust. Flame 159 (6) (2012) 2028-2055]) and iso-pentanol (3-methylbutanol) [Sarathy et al. Combust. Flame 160 (12) (2013) 2712-2728]. Experimentally determined and modeled mole fraction profiles were compared to demonstrate the model\\'s capabilities. Examples of individual mole fraction profiles are discussed together with the most significant fuel consumption pathways to highlight the combustion chemistry of 2-methylbutanol. Discrepancies between experimental and modeling results are used to suggest areas where improvement of the kinetic model would be needed. © 2014.

  12. Review of survey and experimental research that examines the relationship between alcohol consumption and men's sexual aggression perpetration.

    Science.gov (United States)

    Abbey, Antonia; Wegner, Rhiana; Woerner, Jacqueline; Pegram, Sheri E; Pierce, Jennifer

    2014-10-01

    This article systematically reviews empirical studies that examine associations between alcohol consumption and men's sexual aggression with the goal of identifying major findings; gaps in current knowledge; and directions for future research, practice, and policy. We identified 25 cross-sectional surveys, 6 prospective studies, and 12 alcohol administration experiments published between 1993 and August 2013 with male college students and young adult (nonincarcerated) samples. Many cross-sectional surveys have demonstrated that distal and proximal measures of men's alcohol consumption are positively associated with sexual assault perpetration, although very few of these studies evaluated how alcohol interacts with other risk and protective factors to exacerbate or inhibit sexual aggression. There are surprisingly few surveys that examine alcohol's effects at the event level and over short-time intervals to identify how changes in alcohol consumption are associated with changes in perpetration status. Alcohol administration studies suggest some important mechanisms that warrant additional investigation. © The Author(s) 2014.

  13. Review of Survey and Experimental Research That Examines the Relationship Between Alcohol Consumption and Men's Sexual Aggression Perpetration

    Science.gov (United States)

    Abbey, Antonia; Wegner, Rhiana; Woerner, Jacqueline; Pegram, Sheri E.; Pierce, Jennifer

    2015-01-01

    This article systematically reviews empirical studies that examine associations between alcohol consumption and men's sexual aggression with the goal of identifying major findings; gaps in current knowledge; and directions for future research, practice, and policy. We identified 25 cross-sectional surveys, 6 prospective studies, and 12 alcohol administration experiments published between 1993 and August 2013 with male college students and young adult (nonincarcerated) samples. Many cross-sectional surveys have demonstrated that distal and proximal measures of men's alcohol consumption are positively associated with sexual assault perpetration, although very few of these studies evaluated how alcohol interacts with other risk and protective factors to exacerbate or inhibit sexual aggression. There are surprisingly few surveys that examine alcohol's effects at the event level and over short-time intervals to identify how changes in alcohol consumption are associated with changes in perpetration status. Alcohol administration studies suggest some important mechanisms that warrant additional investigation. PMID:24776459

  14. Effect of Korean Red Ginseng in chronic liver disease

    Directory of Open Access Journals (Sweden)

    Tae Young Park

    2017-10-01

    Full Text Available Chronic liver disease, one of the most common diseases, typically arises from nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, or hepatocellular carcinoma. Therefore, there is a pressing need for improved treatment strategies. Korean Red Ginseng has been known to have positive effects on liver disease and liver function. In this paper, we summarize the current knowledge on the beneficial effects of Korean Red Ginseng on chronic liver disease, a condition encompassing nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, and hepatocellular carcinoma, as supported by experimental evaluation and clinical investigation.

  15. Experimental oral transmission of chronic wasting disease to reindeer (Rangifer tarandus tarandus.

    Directory of Open Access Journals (Sweden)

    Gordon B Mitchell

    Full Text Available Chronic wasting disease (CWD, a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrP(CWD in the recto-anal mucosa associated lymphoid tissue (RAMALT of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed disease. Tissue distribution analysis of PrP(CWD in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene (PRNP sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M, 129 (G/S, 138 (S/N and 169 (V/M. These findings demonstrate that (i a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii certain reindeer PRNP polymorphisms may be protective against CWD infection.

  16. Venlafaxine involves nitric oxide modulatory mechanism in experimental model of chronic behavior despair in mice.

    Science.gov (United States)

    Kumar, Anil; Garg, Ruchika; Gaur, Vaibhav; Kumar, Puneet

    2010-01-22

    Present study has been designed to elucidate the nitric oxide modulatory mechanism of venlafaxine in experimental model of chronic behavior despair in mice. Animals (male albino laca mice) were forced to swim daily for 6 min test session for 7 days and immobility period of each animal was measured on every alternate days. Six minutes forced swimming test session for 7 days caused anxiety-like behavior (as assessed by mirror chamber and plus maze tests) and impairment in locomotor activity followed by oxidative damage (increased lipid peroxidation, nitrite concentration, depleted reduced glutathione and catalase activity) as compared to naïve animals. Seven days venlafaxine (5 and 10 mg/kg) treatment significantly caused anti-anxiety-like effect, improved locomotor activity and attenuated oxidative damage (reduced lipid peroxidation, nitrite concentration and caused restoration of reduce glutathione and catalase activity) as compared to control. Caffeine (10 mg/kg) pretreatment with venlfaxine (5 mg/kg) did not produce any significant effect on locomotor activity, immobility period and oxidative damage as compared to their effect per se. Further, L-NAME (5 mg/kg) and methylene blue (10 mg/kg) pretreatment with sub effective dose of venlafaxine (5 mg/kg) potentiated its protective effect which was significant as compared to their effect per se. However, L-arginine (100 mg/kg) pretreatment with venlafaxine (5 mg/kg) significantly reversed the protective effect of venlafaxine (P<0.05). Present study suggests that nitric oxide modulation might be involved in the protective effects of venlafaxine. Copyright 2009 Elsevier B.V. All rights reserved.

  17. Response of chronic gingivitis to hygiene therapy and experimental gingivitis. Clinical, microbiological and metabonomic changes.

    Science.gov (United States)

    Klukowska, Malgorzata; Goyal, C Ram; Khambe, Deepa; Cannon, Michael; Miner, Melanie; Gurich, Nataliya; Circello, Ben; Huggins, Tom; Barker, Matthew L; Furnish, Carrie; Conde, Erinn; Hoke, Phyllis; Haught, Chris; Xie, Sancai; White, Donald J

    2015-10-01

    To compare the clinical, microbiological and metabonomic profiles of subjects with high and low levels of chronic gingival bleeding during a controlled oral hygiene regimen intervention including sequential phases of rigorous therapeutic oral hygiene followed by experimental gingivitis (EG). Two cohorts of qualified study subjects with differences in gingival bleeding on probing levels at their baseline clinical examination were entered into the study. These two cohorts were followed through three separate study phases including a 1-week baseline phase, a 2-week phase of rigorous oral hygiene including dental prophylaxis, and a 3-week EG phase of no oral hygiene to encourage relapse of gingivitis. The 58 subjects were assessed during each phase of the study for clinical presentation of gingivitis and concurrently had plaque sampled for real-time polymerase chain reaction (RTPCR) microbiological characterization and salivary lavage samples for 'systems biology' metabonomics assessment by 1H-NMR. Subjects presenting with different levels of gingival bleeding on probing when they entered the study responded differently to rigorous oral hygiene and EG. Specifically, the high bleeding cohort responded sluggishly to rigorous oral hygiene and exhibited markedly greater relapse to gingivitis during EG. RTPCR analysis showed changes in bacterial populations that were associated with study phases, particularly the increases in putative periodontal pathogens during EG. However, the microbiological profiles of high- and low-susceptibility gingival bleeding patients were largely similar. Metabonomic analysis likewise revealed significant changes in metabolite composition during study phases associated with differences in plaque toxicity, especially the short chain carboxylic acids propionate and n-butyrate, which tracked clinical changes in gingivitis severity. Systems analysis of metabonomic changes suggested differences between cohorts, although analysis to date has not

  18. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    Energy Technology Data Exchange (ETDEWEB)

    Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

  19. [Effect of psychotropic substances on the development of alcoholic motivation in noninbred white rats].

    Science.gov (United States)

    Burov, Iu V; Kampov-Polevoĭ, A V; Nikitina, L N

    1986-03-01

    The experiments have shown the capacity of antidepressant amitriptylin (0.5 mg/kg, i. p.) and tranquilizer phenazepam (0.1 mg/kg i. p.) to normalize the adaptive behaviour and almost completely prevent the development of alcohol motivation in animals with insufficient adaptive behaviour. It was established that in animals initially rejecting alcohol, chronic treatment with these drugs as well as d-amphetamine promoted alcohol motivation. The results obtained have proved our earlier hypothesis that preclinical search for drugs for the prevention and treatment of early stages of alcoholism is possible only in animals pre-selected according to their inclination to experimental alcoholism.

  20. [The state of lipid peroxidation and antioxidant protection system in parietal cells under experimental chronic atrophic gastritis development].

    Science.gov (United States)

    Drobins'ka, O V; Gaĭda, L M; Dvorshchenko, K O; Tymoshenko, M O; Ostapchenko, L I

    2010-01-01

    The lipid peroxidation state and the system functioning of antioxidant protection in parietal cells under rat chronic atrophic gastritis development was investigated. It was detected that the compensatory increase of superoxide dismutase and catalase activity did not affect the lipoperoxidation process and this resulted in accumulation of toxic TBA reactive substances and diene conjugates during the whole stages of the experimental pathology development. It was shown that the reserved power of the glutathione antioxidant system is sufficient to provide adoptable response in the acute period of the disease owing to increasing intracellular found of the reduced glutathione, but it is insufficient to prevent its decreasing in parietal cells in case of the chronic atrophic gastritis development. Our findings suggest that glutathione system is involved in processes of gastric atrophy. The obtained results testify about considerable system dysfunctions of lipid peroxidation and the antioxidant protection in processes of the rat experimental atrophic gastritis development.

  1. Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

    Directory of Open Access Journals (Sweden)

    Eugenia Mata-Greenwood

    2017-05-01

    Full Text Available Background : Hypoxia inducible factor 1 alpha (HIF1A is a master regulator of acute hypoxia; however, with chronic hypoxia, HIF1A levels return to the normoxic levels. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia.Results : We examined the effect of chronic hypoxia (3 days; 0.5% oxygen on human brain micro endothelial cells (HBMEC viability and apoptosis. Hypoxia caused a significant reduction in cell viability and an increase in apoptosis. Next, we examined chronic hypoxia associated changes in transcriptome and genome-wide promoter methylation. The data obtained was compared with 16 other microarray studies on chronic hypoxia. Nine genes were altered in response to chronic hypoxia in all 17 studies. Interestingly, HIF1A was not altered with chronic hypoxia in any of the studies. Furthermore, we compared our data to three other studies that identified HIF-responsive genes by various approaches. Only two genes were found to be HIF dependent. We silenced each of these 9 genes using CRISPR/Cas9 system. Downregulation of EGLN3 significantly increased the cell death under chronic hypoxia, whereas downregulation of ERO1L, ENO2, adrenomedullin, and spag4 reduced the cell death under hypoxia.Conclusions : We provide a core group of genes that regulates cellular acclimatization under chronic hypoxic stress, and most of them are HIF independent.

  2. Support vector machine and fuzzy C-mean clustering-based comparative evaluation of changes in motor cortex electroencephalogram under chronic alcoholism.

    Science.gov (United States)

    Kumar, Surendra; Ghosh, Subhojit; Tetarway, Suhash; Sinha, Rakesh Kumar

    2015-07-01

    In this study, the magnitude and spatial distribution of frequency spectrum in the resting electroencephalogram (EEG) were examined to address the problem of detecting alcoholism in the cerebral motor cortex. The EEG signals were recorded from chronic alcoholic conditions (n = 20) and the control group (n = 20). Data were taken from motor cortex region and divided into five sub-bands (delta, theta, alpha, beta-1 and beta-2). Three methodologies were adopted for feature extraction: (1) absolute power, (2) relative power and (3) peak power frequency. The dimension of the extracted features is reduced by linear discrimination analysis and classified by support vector machine (SVM) and fuzzy C-mean clustering. The maximum classification accuracy (88 %) with SVM clustering was achieved with the EEG spectral features with absolute power frequency on F4 channel. Among the bands, relatively higher classification accuracy was found over theta band and beta-2 band in most of the channels when computed with the EEG features of relative power. Electrodes wise CZ, C3 and P4 were having more alteration. Considering the good classification accuracy obtained by SVM with relative band power features in most of the EEG channels of motor cortex, it can be suggested that the noninvasive automated online diagnostic system for the chronic alcoholic condition can be developed with the help of EEG signals.

  3. The effects of sleep extension on sleep and cognitive performance in adolescents with chronic sleep reduction: an experimental study.

    Science.gov (United States)

    Dewald-Kaufmann, J F; Oort, F J; Meijer, A M

    2013-06-01

    To investigate the effects of gradual sleep extension in adolescents with chronic sleep reduction. Outcome variables were objectively measured sleep and cognitive performance. Participants were randomly assigned to either a sleep extension group (gradual sleep extension by advancing bedtimes in the evening) or to a control group (no instruction). Our sample consisted of 55 adolescents (mean age, 15.44 y; 85.5% girls) with symptoms of chronic sleep reduction (loss of energy, shortness of sleep, sleepiness, and irritation). Sleep was monitored with actigraphy over 3 weeks; the first week was the baseline week and the last two weeks were the experimental weeks. Participants in the experimental group were instructed to extend their sleep during the week by gradually advancing their bedtimes by 5 minutes each night. Additionally participants were asked to prevent bedtime shifts on weekend nights. Cognitive performance was assessed before and after the experimental manipulation. During the last week of the experiment, adolescents in the sleep extension group had earlier bedtimes, earlier sleep onsets, spent more time in bed, and slept longer than adolescents in the control group. These results indicate that the experimental manipulation was successful and that adolescents in the experimental group fell asleep earlier and slept longer than adolescents in the control group. Furthermore some aspects of cognitive performance, especially visuospatial processing, significantly changed in the sleep extension group. Gradual sleep extension has beneficial effects on adolescents' sleep and is related to changes in some aspects of cognitive performance. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. The efficacy of hydro alcoholic extract of Seidlitzia rosmarinus on experimental zoonotic cutaneous leishmaniasis lesions in murine model.

    Science.gov (United States)

    Ahmadi, Maryam; Fata, Abdolmajid; Khamesipour, Ali; Rakhshandeh, Hasan; Miramin Mohammadi, Akram; Salehi, Ghodratollah; Monavari, Hadi

    2014-11-01

    Leishmaniasis is one of the most important parasitic infectious diseases in the world. Since last century, many efforts have been made to control and treat the disease, but appropriate vaccines, pesticides and medicines are not available or even eligible. The purpose of this study was to evaluate the effect of hydro-alcoholic extract of Seidlitzia rosmarinus on the lesions of experimental Cutaneous Leishmaniasis (CL) in Balb/c mice. The population study was 60 Ballb/c mice which divided to 6 groups, all infected with Leishmania major [MRHO/75/IR]. Soon after the ulcer started to appear in the early stage, a dose of provided herbal extract with 5, 10 and 15% concentration applied on each lesion. The surface area of the lesions measured during an interval of 10 days. Direct Giemsa stained smears prepared two and four weeks after treatment. Increasing the mean size of the lesions was statistically significant compared to those in control group (p>0.001). Visceral Leishmaniasis (VL) developed in all of the mice including the control group that received Eucerine alone. Survival rate in group receiving 15% S. rosmarinus extracts showed significantly higher compared to mice in control group (pexperimental CL ulcers of Balb/c mice. Further studies with higher concentrations or nano particles are recommended.

  5. The efficacy of hydro alcoholic extract of Seidlitzia rosmarinus on experimental zoonotic cutaneous leishmaniasis lesions in murine model

    Directory of Open Access Journals (Sweden)

    Maryam Ahmadi

    2014-11-01

    Full Text Available Objective: Leishmaniasis is one of the most important parasitic infectious diseases in the world. Since last century, many efforts have been made to control and treat the disease, but appropriate vaccines, pesticides and medicines are not available or even eligible. The purpose of this study was to evaluate the effect of hydro-alcoholic extract of Seidlitzia rosmarinus on the lesions of experimental Cutaneous Leishmaniasis (CL in Balb/c mice. Materials and Methods: The population study was 60 Ballb/c mice which divided to 6 groups, all infected with Leishmania major [MRHO/75/IR]. Soon after the ulcer started to appear in the early stage, a dose of provided herbal extract with 5, 10 and 15% concentration applied on each lesion. The surface area of the lesions measured during an interval of 10 days. Direct Giemsa stained smears prepared two and four weeks after treatment. Results: Increasing the mean size of the lesions was statistically significant compared to those in control group (p>0.001. Visceral Leishmaniasis (VL developed in all of the mice including the control group that received Eucerine alone. Survival rate in group receiving 15% S. rosmarinus extracts showed significantly higher  compared to mice in control group (p

  6. The need for halothane supplementation of N2O-O2-relaxant anaesthesia in chronic alcoholics.

    Science.gov (United States)

    Tammisto, T; Tigerstedt, I

    1977-01-01

    The demand for intermittant halothane supplementation during N2O-O2-relaxant anaesthesia was studied in 25 alcohlics (annual consumption over 15 1 pure alcohol) scheduled for biliary or gastric surgery. The controls were 45 non-alcoholics and 43 patients with an annual consumption of between 1 to 15 1. Thiopental (3 mg/kg/min) was given for induction. After intubation, halothane supplementation was given in 0.5% concentration for 10-min periods. Standardized criteria for halothane supplementation were various motor and autonomic responses to painful stimuli. Muscular relaxation was kept fairly constant (roughly 90%), as assessed visually with the aid of a peripheral nerve stimulator. The total time for which halothane supplementation was given, expressed as a percentage of the total anaesthesia time, was used as an indication of the need for halothane supplementation. The need for thiopental for induction was not increased to a statistically significant extent in alcoholics, but signs of excitation did occur in 40% as compared with 11% in non-alcoholics (P less than 0.01). The demand for halothane supplementation was higher in alcoholics (47 +/- 4.8%, s.e. mean) than in non-alcoholics (33 +/- 2.3%). This difference, however, was partly due to the higher incidence of gastric surgery, which required more supplementation than biliary surgery. Analysis of the different criteria indicating the need for halothane supplementation revealed that an increase in blood pressure or heart rate was more common in non-alcoholics, whereas motor irritability, sweating and lacrimation were more frequent in alcoholics. Management of the anaesthetic posed no special difficulties in the alcoholics with an estimated mean annual consumption of 32 +/- 4 (s.e. mean) litres of absolute alcohol. Three patients (5% of the alcohol consumers) reported dreams or recollections, suggesting that this mode of halothane supplementation does not guarantee an adequate anaesthetic depth. The difficulties

  7. Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

    Science.gov (United States)

    Varatharajalu, Ravi; Garige, Mamatha; Leckey, Leslie C.; Reyes-Gordillo, Karina; Shah, Ruchi; Lakshman, M. Raj

    2016-01-01

    Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA)) and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA) alcohol-liquid (5%) diets supplemented with or without curcumin (150 mg/kg/day) for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1) mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis. PMID:26881029

  8. PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    M. V. Osikov

    2016-01-01

    Full Text Available The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF. An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes, CD45RA+ (mainly, B cells, as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis, Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells. Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH, IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma

  9. Chronic stress moderates the impact of social exclusion on pain tolerance: an experimental investigation

    National Research Council Canada - National Science Library

    Pieritz K; Schäfer SJ; Strahler J; Rief W; Euteneuer F

    2017-01-01

    ... (ie, heat pain tolerance) and a sensory component of pain (ie, heat pain intensity). Whether a potential effect may be moderated by chronic life stress, social status, or social support was further examined...

  10. Kinesiophobia, catastrophizing and anticipated symptoms before stair climbing in chronic fatigue syndrome: an experimental study.

    NARCIS (Netherlands)

    Nijs, J.; Meeus, M.; Heins, M.; Knoop, H.; Moorkens, G.; Bleijenberg, G.

    2012-01-01

    PURPOSE: Kinesiophobia and catastrophizing are frequent among people with chronic fatigue syndrome (CFS). This study was aimed at examining (1) whether kinesiophobia, anticipated symptoms and fatigue catastrophizing are related to stair climbing performance in people with CFS; and (2) whether

  11. Kinesiophobia, catastrophizing and anticipated symptoms before stair climbing in chronic fatigue syndrome: an experimental study.

    NARCIS (Netherlands)

    Nijs, J.; Meeuw, M.; Heins, M.; Knoop, H.; Moorkens, G.; Bleijenberg, G.

    2012-01-01

    Purpose: Kinesiophobia and catastrophizing are frequent among people with chronic fatigue syndrome (CFS). This study was aimed at examining (1) whether kinesiophobia, anticipated symptoms and fatigue catastrophizing are related to stair climbing performance in people with CFS; and (2) whether

  12. The Proximal Effects of Acute Alcohol Consumption on Male-to-Female Aggression: A Meta-Analytic Review of the Experimental Literature.

    Science.gov (United States)

    Crane, Cory A; Godleski, Stephanie A; Przybyla, Sarahmona M; Schlauch, Robert C; Testa, Maria

    2016-12-01

    The current meta-analytic review examined the experimental literature to quantify the causal effect of acute alcohol consumption on self-reported and observed indicators of male-to-female general, sexual, and intimate partner aggression. Database and reference list searches yielded 22 studies conducted between 1981 and 2014 that met all criteria for inclusion and that were subjected to full text coding for analysis. Results detected a significant overall effect (d = .36), indicating that male participants who consumed alcohol evidenced greater aggressive behavior toward females while completing a subsequent laboratory aggression paradigm than male participants who received no alcohol. We found homogeneity across all categories of potential moderator variables. Results further indicated that alcohol resulted in comparable increases of male-to-female sexual (d = .32) and intimate partner (d = .45) aggression. Further research is required to draw meaningful conclusions about individual and situational factors that may interact with acute alcohol consumption to produce the highest levels of risk. © The Author(s) 2015.

  13. Understanding development and prevention of chronic physical aggression: towards experimental epigenetic studies

    OpenAIRE

    Tremblay, Richard E

    2008-01-01

    The aim of this paper was to highlight how developmental psychopathology, epigenetics and prevention experiments are starting to blend together to explain the developmental causes of chronic physical aggression (CPA) and, more importantly, to help prevent CPA and its associated physical, mental and social problems. After defining the keywords (prevention, chronic and physical aggression), a selected review of published studies is used to answer the following four questions: when should we att...

  14. Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

    Science.gov (United States)

    Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

    2016-05-01

    Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Assessment of scoring systems for acute-on-chronic liver failure at predicting short-term mortality in patients with alcoholic hepatitis.

    Science.gov (United States)

    Kim, Hee Yeon; Kim, Chang Wook; Kim, Tae Yeob; Song, Do Seon; Sinn, Dong Hyun; Yoon, Eileen L; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Kim, Jeong Han; Yim, Hyung Joon; Kim, Sung Eun; Baik, Soon Koo; Lee, Byung Seok; Jang, Jae Young; Kim, Young Seok; Kim, Sang Gyune; Yang, Jin Mo; Sohn, Joo Hyun; Lee, Heon Ju; Park, Seung Ha; Choi, Eun Hee; Kim, Dong Joon

    2016-11-07

    To assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting short-term mortality among patients with alcoholic hepatitis. We retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), CLIF Consortium Organ Failure score (CLIF-C OFs), Maddrey's discriminant function (DF), age, bilirubin, international normalized ratio and creatinine score (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), model for end-stage liver disease (MELD), and MELD-Na. Of 264 patients, 32 (12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86 (0.81-0.90), 0.89 (0.84-0.92), 0.79 (0.74-0.84), 0.78 (0.72-0.83), 0.81 (0.76-0.86), 0.83 (0.78-0.88), and 0.83 (0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality. CLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.

  16. Research on acute and chronic toxity of the experimental drug Аmprolinsyl

    Directory of Open Access Journals (Sweden)

    B. Gutyj

    2017-02-01

    membranes of hepatocytes, which indicates increased activity of aminotransferases.When investigating the chronic toxicity of Amprolinsyl it was found that at doses of 1/50 LD50, and 1/100 LD50 the drug had no effect on the results of functional tests, due to the normal functioning of the liver tissue and the lack of negative impact on animals in the 3rd and 4th groups. Administration of the the drug at doses of 1/20, 1/50 and 1/100 LD50 over 30 days did not significantly affect the functional state of the internal organs of the experimental animals. When investigating the morphological blood parameters of the rats following oral administration of Amprolinsyl at different doses a downward trend in the haemoglobin and colour index value and a likely reduction in the number of white blood cells, compared to the control group was observed in all experimental groups. According to the values of haematological and biochemical parameters, it was established that in spite of the low toxicityof Amprolinsyl at doses of 1/20 and 1/50 LD50 the drug had an effect on lipid metabolism, as was shown following the increase of glycerol.

  17. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Giovanni Musso

    2014-07-01

    Full Text Available BACKGROUND: Chronic kidney disease (CKD is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. METHODS AND FINDINGS: English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR, and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants, we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66 and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95 CKD. Non-alcoholic steatohepatitis (NASH was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05 and incidence (HR 2.12, 95% CI 1.42-3.17 of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3

  18. Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease: A Systematic Review and Meta-analysis

    Science.gov (United States)

    Musso, Giovanni; Gambino, Roberto; Tabibian, James H.; Ekstedt, Mattias; Kechagias, Stergios; Hamaguchi, Masahide; Hultcrantz, Rolf; Hagström, Hannes; Yoon, Seung Kew; Charatcharoenwitthaya, Phunchai; George, Jacob; Barrera, Francisco; Hafliðadóttir, Svanhildur; Björnsson, Einar Stefan; Armstrong, Matthew J.; Hopkins, Laurence J.; Gao, Xin; Francque, Sven; Verrijken, An; Yilmaz, Yusuf; Lindor, Keith D.; Charlton, Michael; Haring, Robin; Lerch, Markus M.; Rettig, Rainer; Völzke, Henry; Ryu, Seungho; Li, Guolin; Wong, Linda L.; Machado, Mariana; Cortez-Pinto, Helena; Yasui, Kohichiroh; Cassader, Maurizio

    2014-01-01

    Background Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. Methods and Findings English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69–2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65–1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58–4.05) and incidence (HR 2.12, 95% CI 1.42–3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14–8

  19. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

    NARCIS (Netherlands)

    Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a

  20. Testing the validity of the Danish urban myth that alcohol can be absorbed through feet: open labelled self experimental study

    DEFF Research Database (Denmark)

    Hansen, Christian Stevns; Færch, Louise; Kristensen, Peter Lommer

    2010-01-01

    To determine the validity of the Danish urban myth that it is possible to get drunk by submerging feet in alcohol.......To determine the validity of the Danish urban myth that it is possible to get drunk by submerging feet in alcohol....

  1. THE DAMAGING EFFECTS OF ALCOHOL: CHRONIC AND PATTERN ALCOHOL USE EXPLAIN WHY SEXUAL ASSAULT FIGURES HAVE NOT SIGNIFICANTLY DROPPED IN THE UNITED STATES MILITARY

    Science.gov (United States)

    2015-10-01

    demographics, prevalence rates of prior military sexual abuse or perpetration, military culture as a promoter, emphasis on violence and hyper... masculinity .22 While it is clear these factors do bare some relevance, it is not the full picture. A Systemic Lens is Required Research on the topic...affect areas of the brain that lead to violence . Alcohol related brain damage during adolescence further sets the stage for antisocial behavior and

  2. The corticotropin releasing hormone-1 (CRH1) receptor antagonist pexacerfont in alcohol dependence: a randomized controlled experimental medicine study.

    Science.gov (United States)

    Kwako, Laura E; Spagnolo, Primavera A; Schwandt, Melanie L; Thorsell, Annika; George, David T; Momenan, Reza; Rio, Daniel E; Huestis, Marilyn; Anizan, Sebastien; Concheiro, Marta; Sinha, Rajita; Heilig, Markus

    2015-03-13

    Extensive preclinical data implicate corticotropin-releasing hormone (CRH), acting through its CRH1 receptor, in stress- and dependence-induced alcohol seeking. We evaluated pexacerfont, an orally available, brain penetrant CRH1 antagonist for its ability to suppress stress-induced alcohol craving and brain responses in treatment seeking alcohol-dependent patients in early abstinence. Fifty-four anxious alcohol-dependent participants were admitted to an inpatient unit at the NIH Clinical Center, completed withdrawal treatment, and were enrolled in a double-blind, randomized, placebo-controlled study with pexacerfont (300 mg/day for 7 days, followed by 100 mg/day for 23 days). After reaching steady state, participants were assessed for alcohol craving in response to stressful or alcohol-related cues, neuroendocrine responses to these stimuli, and functional magnetic resonance imaging (fMRI) responses to alcohol-related stimuli or stimuli with positive or negative emotional valence. A separate group of 10 patients received open-label pexacerfont following the same dosing regimen and had cerebrospinal fluid sampled to estimate central nervous system exposure. Pexacerfont treatment had no effect on alcohol craving, emotional responses, or anxiety. There was no effect of pexacerfont on neural responses to alcohol-related or affective stimuli. These results were obtained despite drug levels in cerebrospinal fluid (CSF) that predict close to 90% central CRH1 receptor occupancy. CRH1 antagonists have been grouped based on their receptor dissociation kinetics, with pexacerfont falling in a category characterized by fast dissociation. Our results may indicate that antagonists with slow offset are required for therapeutic efficacy. Alternatively, the extensive preclinical data on CRH1 antagonism as a mechanism to suppress alcohol seeking may not translate to humans.

  3. An experimental test of assessment reactivity within a web-based brief alcohol intervention study for college students.

    Science.gov (United States)

    Fazzino, Tera L; Rose, Gail L; Helzer, John E

    2016-01-01

    Web-based brief alcohol intervention (WBI) programs have efficacy in a wide range of college students and have been widely disseminated to universities to address heavy alcohol use. In the majority of efficacy studies, web-based research assessments were conducted before the intervention. Web-based research assessments may elicit reactivity, which could inflate estimates of WBI efficacy. The current study tested whether web-based research assessments conducted in combination with a WBI had additive effects on alcohol use outcomes, compared to a WBI only. Undergraduate students (n=856) from universities in the United States and Canada participated in this online study. Eligible individuals were randomized to complete 1) research assessments+WBI or 2) WBI-only. Alcohol consumption, alcohol-related problems, and protective behaviors were assessed at one-month follow up. Multiple regression using 20 multiply imputed datasets indicated that there were no significant differences at follow up in alcohol use, alcohol-related problems, or protective behaviors used when controlling for variables with theoretical and statistical relevance. A repeated measures analysis of covariance revealed a significant decrease in peak estimated blood alcohol concentration in both groups, but no differential effects by randomized group. There were no significant moderating effects from gender, hazardous alcohol use, or motivation to change drinking. Web-based research assessments combined with a web-based alcohol intervention did not inflate estimates of intervention efficacy when measured within-subjects. Our findings suggest universities may be observing intervention effects similar to those cited in efficacy studies, although effectiveness trials are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine.

    Science.gov (United States)

    Prkacin, I; Separovic, J; Aralicia, G; Perovic, D; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Staresinic, M; Anic, T; Mikus, D; Sikiric, P; Seiwerth, S; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sebecic, B; Boban-Blagaic, A; Kokic, N

    2001-01-01

    Liver lesions and portal hypertension in rats, following chronic alcohol administration, are a particular target for therapy. Portal hypertension (mm Hg) assessed directly into the portal vein, and liver lesions induced by 7.28 g/kg b.w. of alcohol given in drinking water for 3 months, were counteracted by a stable gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in a variety of models of gastrointestinal or liver lesions (10 microg or 10 ng/kg b.w. i.p. or i.g.) and propranolol (10 mg/kg b.w. i.g.), but not ranitidine (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). The medication (once daily) was throughout either the whole 3 months period (1) or the last month only (2) (last application 24 h before sacrifice). In the background of 7.28 g/kg/daily alcohol regimen similar lesions values were assessed in control rats following alcohol consumption, after 2 or 3 months of drinking. Both prophylactic and therapeutic effects were shown. After a period of 2 or 3 months, in all control saline [intragastrically (i.g.) or intraperitoneally (i.p.)] treated rats, the applied alcohol regimen consistently induced a significant rise of portal blood pressure values over values noted in healthy rats. In rats that received gastric pentadecapeptide BPC 157 or propranolol the otherwise raised portal pressure was reduced to the values noted in healthy rats. Besides, a raised surface area (microm(2)) and increased circumference (microm) of hepatocyte or hepatocyte nucleus [HE staining, measured using PC-compatible program ISSA (VAMS, Zagreb, Croatia)] and an advanced steatosis [scored (0-4), Oil Red staining] (on 100 randomly assigned hepatocytes per each liver), an increased liver weight, all together parallel a raised portal pressure in controls. Some of them were completely eliminated (not different from healthy rats, i.e. portal pressure, the circumference and area of hepatocytes, liver weight), while others were

  5. Alcohol and HCV Chronic Infection Are Risk Cofactors of Type 2 Diabetes Mellitus for Hepatocellular Carcinoma in Italy

    Science.gov (United States)

    Balbi, Massimiliano; Donadon, Valter; Ghersetti, Michela; Grazioli, Silvia; Valentina, Giovanni Della; Gardenal, Rita; Mas, Maria Dal; Casarin, Pietro; Zanette, Giorgio; Miranda, Cesare; Cimarosti, Paolo

    2010-01-01

    Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection. PMID:20617035

  6. Are there possibilities for the detection of chronically elevated alcohol consumption by hair analysis? A report about the state of investigation.

    Science.gov (United States)

    Pragst, F; Spiegel, K; Sporkert, F; Bohnenkamp, M

    2000-01-10

    The analysis of suitable ethanol markers in hair would be an advantageous tool for chronic alcohol abuse control because of the wide diagnostic window allowed by this specimen and the possibility of segmental investigation. Between the markers practically used or thoroughly investigated in blood or urine, ethylglucuronide, fatty acid ethylesters, phosphatidylethanol, acetaldehyde adducts to protein and 5-hydroxytryptophol can be regarded as possible candidates also in hair, but preliminary data were found in the literature only for ethylglucuronide and acetaldehyde modified proteins. By using headspace gas chromatography and headspace solid phase microextraction in combination with gas chromatography-mass spectrometry (SPME-GC/MS), in alkaline hydrolysates of hair it was possible to determine between 17 and 135 ng/mg of ethanol beside acetone and several other volatile compounds with slightly higher ethanol values for alcoholics than for social drinkers and teetotalers. A part of this is ethanol only absorbed in the hair matrix from the surrounding environment and consequently is not applicable as a diagnostic criterion. By extraction with aqueous buffer, methanol or a methanol/chloroform mixture and subsequent alkaline hydrolysis it was found that another part is generated from ethylesters, which are preferentially deposited in the lipid fraction of hair. In a specific search for ethylesters of 17 carboxylic acids by GC/MS-SIM in most cases ethyl 4-hydroxybenzoate (0.1 to 5.9 ng/mg, a preservative in hair cosmetics) and in four cases traces of indolylacetic acid ethylester were found. Furthermore, diethyl phthalate (a softening agent, present also in many cosmetic products) was identified in the hair of alcoholics as well as of children. As potential markers of alcohol intake, ethyl palmitate, ethyl stearate and ethyl oleate were detected in hair samples of alcoholics by headspace SPME-GC/MS of the chloroform/methanol extracts.

  7. Long-Term γ-Hydroxybutyric Acid (GHB and Disulfiram Combination Therapy in GHB Treatment-Resistant Chronic Alcoholics

    Directory of Open Access Journals (Sweden)

    Icro Maremmani

    2011-07-01

    Full Text Available Leading Italian studies support the use of γ-hydroxybutyric acid (GHB, not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30–40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of ‘antagonist’ effect by using the ‘psychological threat’ of disulfiram (adversative effect while taking advantage of the anticraving effect of GHB, despite the limitation of its ‘non-blockade’ effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4% successfully completed the protocol and were considered to be responders; 18 (34.6% left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

  8. The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol - a randomized study.

    Science.gov (United States)

    Dart, R C; Green, J L; Kuffner, E K; Heard, K; Sproule, B; Brands, B

    2010-08-01

    Retrospective accounts suggest that therapeutic doses of paracetamol can produce severe hepatic injury in patients with putative high-risk conditions, including alcoholism and infectious hepatitis. Metabolism of paracetamol to its hepatotoxic metabolite is enhanced in patients who abuse alcohol, who also have compromised liver defences from depressed hepatic glutathione. To determine the effect of paracetamol on serum liver tests of newly abstinent subjects who abuse alcohol, including subjects with hepatitis C infection. A randomized, double-blind, placebo-controlled study. Adult alcohol abusers with a current drinking episode longer than 7 days received either placebo or paracetamol 4 g/day for 5 days. Of 142 subjects enrolled, 74 received paracetamol and 68 received placebo. Mean ALT activity during treatment increased from 48 to 62 IU/L in the paracetamol group and from 47 to 49 IU/L in the placebo group. Maximum ALT was 238 and 249 IU/L in the paracetamol and control groups respectively. The INR remained unchanged and serum bilirubin decreased in both groups. Subgroup analyses for subjects with alcoholic hepatitis, hepatitis C virus antibody and other subgroups showed no statistical difference between groups. Administration of paracetamol 4 g/day appears safe in newly abstinent patients who abuse alcohol.

  9. Chronic blockade of angiotensin II action prevents glomerulosclerosis, but induces graft vasculopathy in experimental kidney transplantation

    NARCIS (Netherlands)

    Smit-van Oosten, A; Navis, G; Stegeman, CA; Joles, JA; Klok, PA; Kuipers, F; Tiebosch, ATMG; van Goor, H

    Long-term renin-angiotensin system blockade is beneficial in a variety of renal diseases, This study examines the long-term (34 weeks) effects of the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor type I blocker L158,809 in the Fisher to Lewis rat model of chronic

  10. Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

    Science.gov (United States)

    The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential ...

  11. Liver and kidney toxicity in chronic use of opioids: An experimental ...

    Indian Academy of Sciences (India)

    In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group ( = 10).

  12. Shared immune and repair markers during experimental toxoplasma chronic brain infection and schizophrenia

    NARCIS (Netherlands)

    J.J. Tomasik (Jakub); T.L. Schultz (Tracey L.); W. Kluge (Wolfgang); R.H. Yolken (Robert H.); S. Bahn (Sabine); V.B. Carruthers (Vern B.)

    2016-01-01

    textabstractChronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse

  13. Antinociceptive activity of acute and chronic administration of Murraya koenigii L. leaves in experimental animal models.

    Science.gov (United States)

    Patil, Rupali Arun; Langade, Padmaja Mukund; Dighade, Pramod Babarao; Hiray, Yogesh Ashok

    2012-01-01

    To evaluate the antinociceptive activity of acute and chronic administration of petroleum ether extract of Murraya koenigii L. leaves (PMK) and total alkaloids separated from petroleum ether extract of Murraya koenigii leaves (AMK) in mice. PMK was subjected for isolation of total alkaloid fraction AMK. The antinociceptive activity of PMK (100 and 300 mg/kg, p.o.) and AMK (100 and 300 mg/kg, p.o.), after acute and chronic administration (for 15 days), was evaluated using peripheral model like acetic acid-induced writhing method and central model like hot plate method and tail immersion method. Statistical analysis was carried out by one-way ANOVA followed by Dunnett's test. In acute studies, PMK and AMK significantly and dose-dependently reduced the number of acetic acid-induced writhing, significantly increased the latency of paw licking in hot plate method, and significantly increased the basal reaction time in tail immersion method. With chronic administration of PMK and AMK, highest activity was observed on day 9 in acetic acid-induced writhing model. In hot plate and tail immersion method, chronic administration of PMK and AMK initially showed fluctuating responses but produced highest degree of antinociception on day 9 of the study. The degree of antinociception produced by PMK and AMK at the end of 15 days study suggest that Murraya koenigii has potential to use as an analgesic.

  14. Liver and kidney toxicity in chronic use of opioids: An experimental ...

    Indian Academy of Sciences (India)

    Unknown

    In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group (n = 10).

  15. Effects of amlodipine on endothelial function in rats with chronic heart failure after experimental myocardial infarction

    NARCIS (Netherlands)

    deVries, RJM; Anthonio, R; vanVeldhuisen, DJ; Buikema, H; vanGilst, WH

    1997-01-01

    In chronic heart failure, the role of endothelial dysfunction is not yet well established. As calcium metabolism plays an important role in the endothelium, it might be suggested that calcium channel blockers influence endothelial function. Although calcium channel blockers are generally

  16. Review of Survey and Experimental Research That Examines the Relationship Between Alcohol Consumption and Men's Sexual Aggression Perpetration

    OpenAIRE

    ABBEY, ANTONIA; Wegner, Rhiana; Woerner, Jacqueline; Pegram, Sheri E.; Pierce, Jennifer

    2014-01-01

    This article systematically reviews empirical studies that examine associations between alcohol consumption and men's sexual aggression with the goal of identifying major findings; gaps in current knowledge; and directions for future research, practice, and policy. We identified 25 cross-sectional surveys, 6 prospective studies, and 12 alcohol administration experiments published between 1993 and August 2013 with male college students and young adult (nonincarcerated) samples. Many cross-sect...

  17. Interactive effects of chronic cigarette smoking and age on brain volumes in controls and alcohol-dependent individuals in early abstinence.

    Science.gov (United States)

    Durazzo, Timothy C; Mon, Anderson; Pennington, David; Abé, Christoph; Gazdzinski, Stefan; Meyerhoff, Dieter J

    2014-01-01

    Chronic alcohol-use disorders (AUDs) have been shown to interact with normal age-related volume loss to exacerbate brain atrophy with increasing age. However, chronic cigarette smoking, a highly co-morbid condition in AUD and its influence on age-related brain atrophy have not been evaluated. We performed 1.5 T quantitative magnetic resonance imaging in non-smoking controls [non-smoking light drinking controls (nsCONs); n = 54], smoking light drinking controls (sCONs, n = 34), and one-week abstinent, treatment-seeking alcohol-dependent (ALC) non-smokers (nsALCs, n = 35) and smokers (sALCs, n = 43), to evaluate the independent and interactive effects of alcohol dependence and chronic smoking on regional cortical and subcortical brain volumes, emphasizing the brain reward/executive oversight system (BREOS). The nsCONs and sALCs showed greater age-related volume losses than the nsALCs in the dorsal prefrontal cortex (DPFC), total cortical BREOS, superior parietal lobule and putamen. The nsALCs and sALCs demonstrated smaller volumes than the nsCONs in most cortical region of interests (ROIs). The sCONs had smaller volumes than the nsCONs in the DPFC, insula, inferior parietal lobule, temporal pole/parahippocampal region and all global cortical measures. The nsALCs and sALCs had smaller volumes than the sCONs in the DPFC, superior temporal gyrus, inferior and superior parietal lobules, precuneus and all global cortical measures. Volume differences between the nsALCs and sALCs were observed only in the putamen. Alcohol consumption measures were not related to volumes in any ROI for ALC; smoking severity measures were related to corpus callosum volume in the sCONs and sALCs. The findings indicate that consideration of smoking status is necessary for a better understanding of the factors contributing to regional brain atrophy in AUD. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  18. A new small molecule for treating inflammation and chorioretinal neovascularization in relapsing-remitting and chronic experimental autoimmune uveitis.

    Science.gov (United States)

    Diedrichs-Möhring, Maria; Leban, Johann; Strobl, Stefan; Obermayr, Franz; Wildner, Gerhild

    2014-12-16

    We investigated the effect of PP-001, a new small molecule inhibitor of dihydro-orotate dehydrogenase in two experimental rat experimental autoimmune uveitis (EAU) models: a spontaneously relapsing-remitting model and a monophasic/chronic disease model that results in late chorioretinal neovascularization. Both of the diseases are induced by immunization with autoantigen peptides. Prevention was tested using daily oral applications of PP-001 after immunization with the retinal S-antigen peptide PDSAg (for induction of monophasic uveitis and neovascularization) or the interphotoreceptor retinoid-binding protein peptide R14 (for induction of spontaneously relapsing-remitting EAU). Treatment to inhibit relapses and neovascularization was tested using PP-001 daily after the first attack of R14-induced or after onset of PDSAg-induced EAU. Uveitis was graded clinically and histologically. The effect of PP-001 on cytokine secretion and proliferation was evaluated using rat T-cell lines. Preventive feeding of PP-001 abrogated both types of EAU. Starting treatment after the resolution of the first attack led to a significant reduction of the number and intensity of relapses in R14-induced EAU. PP-001-treatment initiated after onset or after peak of PDSAg-induced EAU significantly reduced neovascularization (as determined by histology). Proliferation of antigen-specific T-cell lines and secretion of IFN-γ, IL-17, IL-10, IP-10, and VEGF were efficiently suppressed by PP-001. We investigated a new dihydroorotate dehydrogenase inhibitor as treatment for primary and recurrent disease in relapsing-remitting and chronic rat models of experimental autoimmune uveitis. The small molecule compound PP-001 suppressed proliferation and cytokine secretion of autoreactive T cells (i.e., IFN-g, IL-17, and VEGF) and chorioretinal neovascularization in chronic EAU. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  19. Experimental and computational study of the effect of alcohols on the solution and adsorption properties of a nonionic symmetric triblock copolymer.

    Science.gov (United States)

    Liu, Xiaomeng; He, Feng; Salas, Carlos; Pasquinelli, Melissa A; Genzer, Jan; Rojas, Orlando J

    2012-02-02

    This study investigates the effect of alcohols on the solution and adsorption properties of symmetric triblock nonionic copolymers comprising blocks of ethylene oxide (EO) and propylene oxide (PO) (EO(37)PO(56)EO(37)). The cloud point, surface tension, critical micelle concentration (CMC), and maximum packing at the air-water interface are determined, and the latter is compared to the amount of polymer that adsorbs from solution onto polypropylene (PP) and cellulose surfaces. The interaction energy and radius of micelles are calculated by using molecular dynamics (MD) simulations. Equivalent MD bead parameters were used in dynamic density functional theory (DDFT) simulations to study the influence of alcohols on the phase behavior of EO(37)PO(56)EO(37) and its adsorption on PP from aqueous solutions. The simulation results agree qualitatively with the experimental observations. Ethanol acts as a good cosolvent for EO(37)PO(56)EO(37) and reduces the amount of EO(37)PO(56)EO(37) that adsorbs on PP surfaces; however, little or no influence is observed on the adsorption on cellulose. Interestingly, longer chain alcohols, such as 1-pentanol, produce the opposite effect. Overall, the solution and adsorption properties of nonionic symmetric triblock copolymers in the presence of alcohols are rationalized by changes in solvency and the hydrophobic effect.

  20. Effects of experimentally necessary changes in husbandry on olfactory memory: Chronic food restriction and social isolation.

    Science.gov (United States)

    Manella, Laura; Woldeyohannes, Leuk; McMahon, Devon; Linster, Christiane

    2016-03-01

    Changes to typical procedures in animal husbandry are often necessary to accommodate the needs of behavioral experiments. Two common changes in husbandry for rodents are light chronic food restriction (to motivate animals in reward-association tasks) and social isolation (to accommodate individual feeding schedules or need to reduce interactions because of implants for example). Each of these intervention individually has been shown to modulate behavioral state and with it performance in behavioral tasks. We here systematically test how social isolation and light chronic food restriction modulate olfactory memory in rats. Our results show a strong modulation of olfactory memory after both types of husbandry interventions. These results suggest that common changes in animal husbandry promote distinct and relevant changes in animal behavior. Copyright © 2015. Published by Elsevier Inc.

  1. Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

    Science.gov (United States)

    Montazeri, Mahbobeh; Ebrahimzadeh, Mohammad Ali; Ahmadpour, Ehsan; Sharif, Mehdi; Sarvi, Shahabeddin

    2016-01-01

    Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine. PMID:27645234

  2. Kinesiophobia, catastrophizing and anticipated symptoms before stair climbing in chronic fatigue syndrome: an experimental study.

    OpenAIRE

    Nijs, J.; Meeuw, M.; Heins, M.; Knoop, H; Moorkens, G.; Bleijenberg, G

    2012-01-01

    Purpose: Kinesiophobia and catastrophizing are frequent among people with chronic fatigue syndrome (CFS). This study was aimed at examining (1) whether kinesiophobia, anticipated symptoms and fatigue catastrophizing are related to stair climbing performance in people with CFS; and (2) whether kinesiophobia and fatigue catastrophizing are related to daily physical activity in CFS. Method: Patients with CFS filled in a set of questionnaires, performed a physical demanding task (two floors stair...

  3. The efficacy of computerized alcohol intervention tailored to drinking motives among college students: a quasi-experimental pilot study.

    Science.gov (United States)

    Canale, Natale; Vieno, Alessio; Santinello, Massimo; Chieco, Francesca; Andriolo, Stefano

    2015-03-01

    Although motivational processes may influence the intervention effects and help prevention programmes identify students at great risk for alcohol-related problems, no computerized alcohol intervention has yet to be tailored to drinking motives. To describe the development and initial pilot testing of a computer-delivered intervention tailored to drinking motives, to prevent alcohol abuse and its adverse consequences among university students in general and among baseline hazardous drinkers specifically. 124 college students attending a public university in northeastern Italy participated in this study in October of 2012 (89.2% female- mean age = 21.64-34% baseline hazardous drinkers). Two classes (one undergraduate, one graduate) were assigned to one of two conditions: intervention and control group. Both groups received profile-specific feedback and then the intervention group received profile-specific online training for 4 weeks. This profile was based on their risk type (high-low) and drinking motives (enhancement-social-conformity-coping). Controlling for corresponding baseline alcohol measures, analyses showed a significant interaction between intervention condition and hazardous drinkers at baseline. For hazardous drinkers at baseline, the alcohol intervention results showed a significant decrease in frequency and quantity of alcohol use at follow-up, while no difference was observed between intervention conditions for non-hazardous drinkers at baseline. The results suggest that hazardous drinkers (college students) who completed the specific training and received personalized feedback seemed to do better on frequency and quantity of alcohol use than hazardous drinkers (college students) who received only personalized feedback. These results seem to provide support for a larger trial of the intervention and for more appropriate evaluations.

  4. Renal heparan sulfate proteoglycans modulate fibroblast growth factor 2 signaling in experimental chronic transplant dysfunction.

    Science.gov (United States)

    Katta, Kirankumar; Boersema, Miriam; Adepu, Saritha; Rienstra, Heleen; Celie, Johanna W A M; Mencke, Rik; Molema, Grietje; van Goor, Harry; Berden, Jo H M; Navis, Gerjan; Hillebrands, Jan-Luuk; van den Born, Jacob

    2013-11-01

    Depending on the glycan structure, proteoglycans can act as coreceptors for growth factors. We hypothesized that proteoglycans and their growth factor ligands orchestrate tissue remodeling in chronic transplant dysfunction. We have previously shown perlecan to be selectively up-regulated in the glomeruli and arteries in a rat renal transplantation model. Using the same model, here we present quantitative RT-PCR profiling data on proteoglycans and growth factors from laser-microdissected glomeruli, arterial tunicae mediae, and neointimae at 12 weeks after transplantation. In glomeruli and neointimae of allografts, selective induction of the matrix heparan sulfate proteoglycan perlecan was observed, along with massive accumulation of fibroblast growth factor 2 (FGF2). Profiling the heparan sulfate polysaccharide side chains revealed conversion from a non-FGF2-binding heparan sulfate phenotype in control and isografted kidneys toward a FGF2-binding phenotype in allografts. In vitro experiments with perlecan-positive rat mesangial cells showed that FGF2-induced proliferation is dependent on sulfation and can be inhibited by exogenously added heparan sulfate. These findings indicate that matrix proteoglycans such as perlecan serve as functional docking platforms for FGF2 in chronic transplant dysfunction. We speculate that heparin-like glycomimetics could be a promising intervention to retard development of glomerulosclerosis and neointima formation in chronic transplant dysfunction. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. Shared Immune and Repair Markers During Experimental Toxoplasma Chronic Brain Infection and Schizophrenia.

    Science.gov (United States)

    Tomasik, Jakub; Schultz, Tracey L; Kluge, Wolfgang; Yolken, Robert H; Bahn, Sabine; Carruthers, Vern B

    2016-03-01

    Chronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse model of chronic T gondii infection to identify protein biomarkers that are altered in serum and brain samples at 2 time points during chronic infection. Furthermore, we compare the identified biomarkers to those differing between "postmortem" brain samples from 35 schizophrenia patients and 33 healthy controls. Our findings suggest that T gondii infection causes substantial and widespread immune activation indicative of neural damage and reactive tissue repair in the animal model that partly overlaps with changes observed in the brains of schizophrenia patients. The overlapping changes include increases in C-reactive protein (CRP), interleukin-1 beta (IL-1β), interferon gamma (IFNγ), plasminogen activator inhibitor 1 (PAI-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular cell adhesion molecule 1 (VCAM-1). Potential roles of these factors in the pathogenesis of schizophrenia and toxoplasmosis are discussed. Identifying a defined set of markers shared within the pathophysiological landscape of these diseases could be a key step towards understanding their specific contributions to pathogenesis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Comparison of the Agar Block and Lieber-DeCarli Diets to Study Chronic Alcohol Consumption in an Aging Model of Fischer 344 Female Rats

    Science.gov (United States)

    Sharda, Daniel R.; Miller-Lee, Jennifer L.; Kanski, Gregory M.; Hunter, J. Craig; Lang, Charles H.; Kennett, Mary J.; Korzick, Donna H.

    2012-01-01

    Introduction Post-menopausal women have a greater risk of developing alcoholic complications compared to age-matched men. Unfortunately, animal models of chronic ethanol consumption with estrogen deficiency are lacking. Here, we characterize the ability of the agar block and Lieber-DeCarli models of chronic ethanol consumption to produce elevated blood alcohol content (BAC) and liver pathology in the F344 postmenopausal animal model of aging. Methods Adult (3 mo) and aged (18 mo) F344 ovary-intact or ovariectomized rats were administered ethanol for 14-20 weeks as follows: diet 1, standard chow access, 10% ethanol in drinking water, and 40% ethanol in agar blocks; diet 2, diet 1 plus low phytoestrogen chow (known to effect ethanol metabolism) for the final 4 weeks; diet 3, Lieber-DeCarli all liquid diet with 36% kcal ethanol. Control animals were matched isocalorically with dextrin. Results For the agar block diet, average BAC was 13 ± 4 mg/dL across groups. BAC was unaffected by reducing dietary phytoestrogen content (12 ± 4 mg/dL), which is known to interfere with ethanol metabolism. Liver pathology was unaffected by the agar block diet. In contrast, the Lieber-DeCarli diet resulted in BAC of 45 ± 5 mg/dL in conjunction with more severe hepatopathology. Discussion We conclude that the Lieber-DeCarli diet produces greater BAC and hepatopathology to study the effects of chronic ethanol administration in the F344 postmenopausal rodent model of aging when compared to an ethanol agar block diet. PMID:22951285

  7. Experimental chronic noise is related to elevated fecal corticosteroid metabolites in lekking male greater Sage-Grouse (Centrocercus urophasianus).

    Science.gov (United States)

    Blickley, Jessica L; Word, Karen R; Krakauer, Alan H; Phillips, Jennifer L; Sells, Sarah N; Taff, Conor C; Wingfield, John C; Patricelli, Gail L

    2012-01-01

    There is increasing evidence that individuals in many species avoid areas exposed to chronic anthropogenic noise, but the impact of noise on those who remain in these habitats is unclear. One potential impact is chronic physiological stress, which can affect disease resistance, survival and reproductive success. Previous studies have found evidence of elevated stress-related hormones (glucocorticoids) in wildlife exposed to human activities, but the impacts of noise alone are difficult to separate from confounding factors. Here we used an experimental playback study to isolate the impacts of noise from industrial activity (natural gas drilling and road noise) on glucocorticoid levels in greater sage-grouse (Centrocercus urophasianus), a species of conservation concern. We non-invasively measured immunoreactive corticosterone metabolites from fecal samples (FCMs) of males on both noise-treated and control leks (display grounds) in two breeding seasons. We found strong support for an impact of noise playback on stress levels, with 16.7% higher mean FCM levels in samples from noise leks compared with samples from paired control leks. Taken together with results from a previous study finding declines in male lek attendance in response to noise playbacks, these results suggest that chronic noise pollution can cause greater sage-grouse to avoid otherwise suitable habitat, and can cause elevated stress levels in the birds who remain in noisy areas.

  8. Treatment with low doses of aspirin during chronic phase of experimental Chagas' disease increases oesophageal nitrergic neuronal subpopulation in mice.

    Science.gov (United States)

    Massocatto, Cristina Lorena; Martins Moreira, Neide; Muniz, Eliane; Marques de Araújo, Silvana; Pinge-Filho, Phileno; Rossi, Robson Marcelo; de Almeida Araújo, Eduardo José; de Mello Gonçales Sant'ana, Débora

    2018-01-19

    Patients with Chagas' disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas' disease on oesophageal function. Twenty male Swiss mice, 60 days of age, were used. The animals were infected with Y strain of Trypanosoma cruzi, injected intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the infected animals, from the 55th to 63rd day after inoculation on consecutive days, and from the 65th to 75th day on alternate days. We investigated food passage of time, wall structure and nitrergic neuronal population of the distal oesophagus. Our data revealed that the use of low doses of aspirin in chronic Chagas' disease caused an increase in the number of nitrergic neurons and partially prevented hypertrophy of the oesophagus. In addition, the aspirin administration impeded Chagas' diseases associated changes in intestinal transit time. Thus treatment with aspirin in the chronic phase of Chagas' disease changes the natural history of the disease and raises the possibility of using it as a new therapeutic approach to the treatment of this aspect of Chagas' disease pathology. © 2018 The Authors. International Journal of Experimental Pathology © 2018 International Journal of Experimental Pathology.

  9. Pentoxifylline reverses chronic experimental Chagasic cardiomyopathy in association with repositioning of abnormal CD8+ T-cell response.

    Directory of Open Access Journals (Sweden)

    Isabela Resende Pereira

    2015-03-01

    Full Text Available Chronic chagasic cardiomyopathy (CCC, the main clinical sign of Chagas disease, is associated with systemic CD8+ T-cell abnormalities and CD8-enriched myocarditis occurring in an inflammatory milieu. Pentoxifylline (PTX, a phosphodiesterase inhibitor, has immunoregulatory and cardioprotective properties. Here, we tested PTX effects on CD8+ T-cell abnormalities and cardiac alterations using a model of experimental Chagas' heart disease.C57BL/6 mice chronically infected by the Colombian Trypanosoma cruzi strain and presenting signs of CCC were treated with PTX. The downmodulation of T-cell receptors on CD8+ cells induced by T. cruzi infection was rescued by PTX therapy. Also, PTX reduced the frequency of CD8+ T-cells expressing activation and migration markers in the spleen and the activation of blood vessel endothelial cells and the intensity of inflammation in the heart tissue. Although preserved interferon-gamma production systemically and in the cardiac tissue, PTX therapy reduced the number of perforin+ cells invading this tissue. PTX did not alter parasite load, but hampered the progression of heart injury, improving connexin 43 expression and decreasing fibronectin overdeposition. Further, PTX reversed electrical abnormalities as bradycardia and prolonged PR, QTc and QRS intervals in chronically infected mice. Moreover, PTX therapy improved heart remodeling since reduced left ventricular (LV hypertrophy and restored the decreased LV ejection fraction.PTX therapy ameliorates critical aspects of CCC and repositioned CD8+ T-cell response towards homeostasis, reinforcing that immunological abnormalities are crucially linked, as cause or effect, to CCC. Therefore, PTX emerges as a candidate to treat the non-beneficial immune deregulation associated with chronic Chagas' heart disease and to improve prognosis.

  10. LINGO-1-Fc-Transduced Neural Stem Cells Are Effective Therapy for Chronic Stage Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Li, Xing; Zhang, Yuan; Yan, Yaping; Ciric, Bogoljub; Ma, Cun-Gen; Chin, Jeannie; Curtis, Mark; Rostami, Abdolmohamad; Zhang, Guang-Xian

    2017-08-01

    The chronic stage multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), remains refractory to current treatments. This refractory nature may be due to the fact that current treatments are primarily immunomodulatory, which prevent further demyelination but lack the capacity to promote remyelination. Several approaches, including transplantation of neural stem cells (NSCs) or antagonists to LINGO-1, a key part of the receptor complex for neuroregeneration inhibitors, have been effective in suppressing the acute stage of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, their effect on the chronic stage EAE is not known. Here, we show that transplantation of NSCs had only a slight therapeutic effect when treatment started at the chronic stage of EAE (e.g., injected at day 40 postimmunization). However, NSCs engineered to produce LINGO-1-Fc, a soluble LINGO-1 antagonist, significantly promoted neurological recovery as demonstrated by amelioration of clinical signs, improvement in axonal integrity, and enhancement of oligodendrocyte maturation and neuron repopulation. Significantly enhanced NAD production and Sirt2 expression were also found in the CNS of mice treated with LINGO-1-Fc-producing NSC. Moreover, differentiation of LINGO-1-Fc-producing NSCs into oligodendrocytes in vitro was largely diminished by an NAMPT inhibitor, indicating that LINGO-1-Fc enhances the NAMPT/NAD/Sirt2 pathway. Together, our study establishes a CNS-targeted, novel LINGO-1-Fc delivery system using NSCs, which represents a novel and effective NSC-based gene therapy approach for the chronic stage of MS.

  11. The iron cycle in chronic kidney disease (CKD): from genetics and experimental models to CKD patients

    Science.gov (United States)

    Zumbrennen-Bullough, Kimberly; Babitt, Jodie L.

    2014-01-01

    Iron is essential for most living organisms but iron excess can be toxic. Cellular and systemic iron balance is therefore tightly controlled. Iron homeostasis is dysregulated in chronic kidney disease (CKD) and contributes to the anemia that is prevalent in this patient population. Iron supplementation is one cornerstone of anemia management in CKD patients, but has not been rigorously studied in large prospective randomized controlled trials. This review highlights important advances from genetic studies and animal models that have provided key insights into the molecular mechanisms governing iron homeostasis and its disturbance in CKD, and summarizes how these findings may yield advances in the care of this patient population. PMID:24235084

  12. Applicability of the Rivermead Behavioural Memory Test - Third Edition (RBMT-3) in Korsakoff's syndrome and chronic alcoholics

    NARCIS (Netherlands)

    Wester, A.J.; Herten, J.C. van; Egger, J.I.; Kessels, R.P.C.

    2013-01-01

    PURPOSE: To examine the applicability of the newly developed Rivermead Behavioural Memory Test - Third Edition (RBMT-3) as an ecologically-valid memory test in patients with alcohol-related cognitive disorders. PATIENTS AND METHODS: An authorized Dutch translation of the RBMT-3 was developed,

  13. Applicability of the Rivermead Behavioural Memory Test - Third Edition (RBMT-3) in Korsakoff's syndrome and chronic alcoholics

    NARCIS (Netherlands)

    Wester, A.J.; Herten, J.C. van; Egger, J.I.M.; Kessels, R.P.C.

    2013-01-01

    Purpose: To examine the applicability of the newly developed Rivermead Behavioural Memory Test – Third Edition (RBMT-3) as an ecologically-valid memory test in patients with alcohol-related cognitive disorders. Patients and methods: An authorized Dutch translation of the RBMT-3 was developed,

  14. SUB CHRONIC TOXICITY TEST FROM ALKOHOL EXTRACT PALIASA LEAVES (Kleinhovia Hospita Linn TO HEPAR/LIVER AND KIDNEY OF EXPERIMENTAL MICE

    Directory of Open Access Journals (Sweden)

    Raflizar Raflizar

    2012-09-01

    Full Text Available Paliasa leaves used to be a traditional medicine for hepatic/ lever desease, so need to maintain the secure & health from the user of this medicine, the aim of the research is to find the dava of ub chronic toxicity from 70% alcohol extract paliasa leaves for experimental mice. The research use amount 30 of 40 months white male mice wistar strain, which have weight in average (SD about 208,75 ±17,47 gr. The extract was given by oral through the spuit for 12 weeks ( 3 months for every mice. After that, all of mice had been killed by ether liquid, andfor histology examination, the blood had been taken from the mice's heart, liver & kidney. The research had been conduct with completed random design includes 5 treatments & 6 repeats. Each treatment includes give the mice aquades with dosage 0 mg/kg body weight (control for 1st group paliasa leaves extract with dosage 250 mg/kg body weight for 2nd group, 3rd group with dosage 500 mg/kg body weight, 4th group with dosage 750 mb/kg body weight & for 5th group with dosage 1000 mg/kg body weight. SGOT, SGPT, Bilirubin direct& indirect, creatinin, ureum kidney & liver cell destruction had been measured from all of groups. The result shows that from eight parameters, in statistically, there are no significant differences between each treatment. The conclution is paliasa leaves extract still save in every treatment dosage. Key words : Toxicity, Electract Paliasa Leaves, Kidney

  15. Validation of an Experimental Model to Study Less Severe Chronic Renal Failure.

    Science.gov (United States)

    Fernandes-Charpiot, Ida Mária Maximina; Caldas, Heloisa Cristina; Mendes, Glória Elisa Florido; Gomes de Sá Neto, Luiz; Oliveira, Henrique Lacativa; Baptista, Maria Alice Sperto Ferreira; Abbud-Filho, Mario

    2016-10-01

    The 5/6 nephrectomy, mimics the stages of human chronic renal failure (CRF), but the procedure causes severe renal functional and morphological damage that could interfere with the evaluation of therapies for slowing the progression of the disease. This study summarizes the results of renal function, histology, and immunohistochemical findings in rats undergoing a 2/3 nephrectomy. The rats were distributed in groups according to the type of nephrectomy: CRF5/6: induced by a 5/6 renal mass reduction and CRF2/3: less severe CRF. The body weight and blood pressure were monitored, and the serum creatinine (SCr), creatinine clearance (CCr), urine osmolality, and 24-h proteinuria (PT24h) were measured. CRF progression was evaluated by the rate of decline of CCr (RCCr). Histology and immunohistochemistry were performed in the remnant kidneys. Statistical analysis was done by unpaired t-test, and a P-value renal histopathological findings revealed fewer chronic lesions in rats with CRF2/3. Similarly, we observed less macrophage accumulation as well as lower proliferative activity and expression of fibronectin and a-smooth muscle-actin in the CRF2/3 model. The CRF2/3 model presented with a pattern of less severe CRF, functionally and morphologically, compared to the classical CRF5/6 model, and the CRF2/3 model may be useful for evaluating therapeutic interventions that target the early stages of CRF.

  16. [Trace elements in the pathogenesis and treatment of chronic bronchitis (a clinico-experimental study)].

    Science.gov (United States)

    Tadzhiev, F S

    1991-01-01

    Experiments on healthy male rats and those with chronic inflammation in the bronchi (CIB) were made to measure the content of testosterone, estradiol, zinc and copper in the blood and in the liquid of bronchoalveolar lavage (LBAL) as well as in the vitally important organs. Attempts were also made to equalize the content of trace elements by means of medicamentous correction in patients suffering from chronic obstructive bronchitis (COB). In CIB, there was a decrease of testosterone concentration in the blood and of zinc concentration in the plasma and formed elements of the blood, lungs, heart, liver, testes and adrenals (p less than 0.05). The zinc level in the LBAL was two times higher, that of copper was three times lower. After zinc sulfate was included into a complex of treatment measures for COB patients, zinc and copper concentrations in the plasma and formed elements of the blood returned to normal in addition to the improvement of the general health status. In the reference group of patients who received conventional symptomatic treatment, the given parameters did not noticeably change.

  17. Neuromechanical responses after biofeedback training in participants with chronic low back pain: an experimental cohort study.

    Science.gov (United States)

    Pagé, Isabelle; Marchand, Andrée-Anne; Nougarou, François; O'Shaughnessy, Julie; Descarreaux, Martin

    2015-09-01

    The objective of this study was to evaluate changes in neuromechanical responses and clinical outcomes in chronic low back pain participants after 4 sessions of biofeedback training. Twenty-one participants took part in an electromyography biofeedback 4-session training program aimed at reducing lumbar paraspinal muscle activity during full trunk flexion. The sessions consisted of ~46 trunk flexion-extension divided into 5 blocks. The effects of training blocks and sessions on lumbar flexion-relaxation ratio and lumbopelvic ranges of motion were assessed. Changes in disability (Oswestry Disability Index), pain intensity (numerical rating scale), and fear of movement (Tampa Scale for Kinesiophobia) were also evaluated. Analyses of variance revealed a significant block effect for which an increase in the flexion-relaxation ratio and the lumbar range of motion between block 1 and the other blocks for sessions 1 and 2 (P Biofeedback training led to decreases in lumbar paraspinal muscle activity in full trunk flexion and increases in lumbopelvic range of motion in participants with chronic nonspecific low back pain. Although the neuromechanical changes were mostly observed at the early stage of the program, the presence of a decrease in the fear of movement suggests that the participants' initially limited ROMs may have been modulated by fear avoidance behaviors. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  18. An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study

    Directory of Open Access Journals (Sweden)

    Mallia Patrick

    2006-09-01

    Full Text Available Abstract Background Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists. Methods We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II. Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage. Results All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1. There were no severe exacerbations or other adverse events. Conclusion Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation.

  19. Limited theraputic effect of n-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis

    Science.gov (United States)

    Alcohol-related steatohepatitis is associated with increased oxidative stress, DNA damage, lipotoxicity, and insulin resistance in liver. Hypothesis: Since inflammation and oxidative stress can promote insulin resistance, effective treatment with anti-oxidants, e.g. N-acetylcysteine (NAC), may rest...

  20. Decision-Making, Cognitive Distortions and Alcohol Use in Adolescent Problem and Non-problem Gamblers: An Experimental Study.

    Science.gov (United States)

    Ciccarelli, Maria; Griffiths, Mark D; Nigro, Giovanna; Cosenza, Marina

    2016-12-01

    In the psychological literature, many studies have investigated the neuropsychological and behavioral changes that occur developmentally during adolescence. These studies have consistently observed a deficit in the decision-making ability of children and adolescents. This deficit has been ascribed to incomplete brain development. The same deficit has also been observed in adult problem and pathological gamblers. However, to date, no study has examined decision-making in adolescents with and without gambling problems. Furthermore, no study has ever examined associations between problem gambling, decision-making, cognitive distortions and alcohol use in youth. To address these issues, 104 male adolescents participated in this study. They were equally divided in two groups, problem gamblers and non-problem gamblers, based on South Oaks Gambling Screen Revised for Adolescents scores. All participants performed the Iowa gambling task and completed the Gambling Related Cognitions Scale and the alcohol use disorders identification test. Adolescent problem gamblers displayed impaired decision-making, reported high cognitive distortions, and had more problematic alcohol use compared to non-problem gamblers. Strong correlations between problem gambling, alcohol use, and cognitive distortions were observed. Decision-making correlated with interpretative bias. This study demonstrated that adolescent problem gamblers appear to have the same psychological profile as adult problem gamblers and that gambling involvement can negatively impact on decision-making ability that, in adolescence, is still developing. The correlations between interpretative bias and decision-making suggested that the beliefs in the ability to influence gambling outcomes may facilitate decision-making impairment.