Monthly Archives: December 2013

Pellagra Encephalopathy in the Context of Alcoholism: Review and Case Report

  1. Marta López1,*,
  2. José M. Olivares1 and
  3. German E. Berrios2
  1. 1Department of Psychiatry, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
  2. 2Robinson College, University of Cambridge, Cambridge, UK
  1. *Corresponding author: Servicio de Psiquiatría, Hospital Meixoeiro, Complejo Hospitalario Universitario de Vigo, Avda. do Meixoeiro, s/n, 36214 Vigo, Spain. Tel.: +34-986811150; E-mail: marta.lopez.almarza{at}gmail.com
  • Received February 11, 2013.
  • Revision requested April 12, 2013.
  • Revision received April 15, 2013.
  • Accepted June 11, 2013.

Aims: The aim of the study was to review and describe the Alcoholic Pellagra Encephalopathy, a severe neuropsychiatric condition caused by a combination of niacin (vitamin B3) deficiency and alcohol abuse. Methods: PsychInfo, Medline and Embase databases were searched for peer-reviewed studies addressing this illness. Results: A historical and conceptual review of the psychopathological aspects of this condition is offered, followed by the report of a patient with a history of chronic alcohol consumption showing signs of pellagra, delusions and visual hallucinations, which was treated successfully with niacin. Conclusion: Pellagra encephalopathy should still be considered in the differential diagnosis of acute psychotic disorders seen in the context of chronic alcoholism.

The Relationship Between Midlife and Late Life Alcohol Consumption, APOE e4 and the Decline in Learning and Memory Among Older Adults

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  1. Brian Downer1,*,
  2. Faika Zanjani2 and
  3. David W. Fardo3
  1. 1Graduate Center for Gerontology, University of Kentucky College of Public Health, J524, KY Clinic, 740 South Limestone, Lexington, KY 40536-0284, USA
  2. 2SPHL-Behavioral & Community Health, University of Maryland, 2387 School of Public Health Building College Park, MD 20742-2611, USA
  3. 3Department of Biostatistics, University of Kentucky College of Public Health, Suite 205, 725 Rose Street, Lexington, KY 40536-0082, USA
  1. *Corresponding author: Graduate Center for Gerontology, University of Kentucky College of Public Health, 740 South Limestone, J524 KY Clinic, Lexington, KY, 40536-0284, USA. Tel: +1-859-218-0148; Fax: +1-859-323-5747; E-mail: brian.downer3{at}uky.edu
  • Received May 2, 2013.
  • Revision requested June 28, 2013.
  • Revision received August 15, 2013.
  • Accepted August 23, 2013.

Abstract

Aims: The aim of the study was to determine whether the trajectory of learning and memory is modified according to an interaction between midlife or late life alcohol consumption status and the presence of one or more APOE e4 alleles. Methods: This was a secondary analysis of cognitive, genetic and alcohol consumption data collected from members of the Framingham Heart Study Offspring Cohort. Results: Light and moderate alcohol consumption during late life was associated with greater decline in learning and memory among APOE e4 carriers, whereas light and moderate alcohol consumption was associated with an increase in learning and memory among non-APOE e4 carriers. There was not a significant interaction between midlife alcohol consumption status and APOE e4 on the trajectory of learning and memory. Conclusion: Light to moderate alcohol consumption during late life may protect against a decline in learning and memory for non-APOE e4 allele carriers, but not for older adults who carry one or more APOE e4 alleles.

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

Glycosylation Changes in the Salivary Glycoproteins of Alcohol-Dependent Patients: A Pilot Study

Aim: Glycosylation of serum proteins is affected with prolonged heavy drinking, and carbohydrate deficient transferrin (CDT) is well established and highly specific biomarker of sustained alcohol consumption. However, total amount of sialic acid is not the only glycoepitope that may be altered as a result of the disease. This work is focused on glycan structures altered in salivary glycoproteins of alcoholics, indicating the most efficient carriers of such marker glycoepitopes. Methods: Salivary glycoproteins of 31 alcohol-dependent patients and 21 healthy controls were studied by means of lectin ELISA and lectin blotting with the lectins specific for core and antennary fucose, α2,3-bound sialic acid as well as T and Tn antigens in O-glycans. Results: In direct lectin ELISA, core fucosylation, α2,3 sialylation and expression of T-antigen were significantly lowered in the saliva of alcohol-dependent patients. In lectin blotting ten glycoprotein bands were analyzed. The profile of disease-related alterations was found to be complex, but all six lectins studied here were able to detect altered glycan structures. In some glycoproteins the tendency to correct the glycosylation profile was observed after 7 weeks of abstinence. Conclusion: Alterations in the glycosylation profiles in the salivary glycoproteins of alcohol-dependent people were found. Some of salivary glycoproteins, such as α-amylase, clusterin, haptoglobin, heavy and light chains of immunoglobulins, and transferrin, seem to be worthy of detailed glycosylation analysis in the detection of alcohol dependence. Further studies may allow one to estimate if such glycomarkers may also reflect the amount of alcohol intake or the duration of alcohol intake.

Notch1-Nuclear Factor {kappa}B Involves in Oxidative Stress-Induced Alcoholic Steatohepatitis

  1. Chen Wang,
  2. Xin Li,
  3. Hongyan Wang,
  4. Qiao Xie and
  5. Youqing Xu*
  1. Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China
  1. *Corresponding author: Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, 6 Xili, Tiantan, Dongcheng District, Beijing 100050, P. R. China. Tel.: +86-10-67096644; Fax: +86-10-67036038; E-mail: youqingxuu{at}hotmail.com
  • Received April 30, 2013.
  • Revision requested June 28, 2013.
  • Revision received July 18, 2013.
  • Accepted September 4, 2013.

Aims: The Notch1 signaling pathway is implicated in multiple inflammatory diseases. However, the role of Notch1 signaling in alcoholic steatohepatitis (ASH) has not been fully investigated. We aimed to determine whether Notch1-Nuclear factor-κB (NF-κB) signaling mediates oxidative stress-induced ASH. Methods: In vitro, three cell lines were used: the HepG2 cells, HepG2 cells transfected with a control vector (Neo cells) and HepG2 cells transfected with a cytochrome P4502E1-expression vector (2E1 cells), which allows the cells to undergo oxidative stress in response to ethanol. All three cell lines were incubated with ethanol with/without Notch1 inhibitor treatment, oxidative stress marker, steatohepatitis marker and Notch1-NF-κB signaling were assessed. To further test Notch1-NF-κB signaling in vivo, rats were fed with ethanol, ethanol plus Notch1 inhibitor or an isocaloric diet for 8 weeks. Hepatitis, oxidative stress and Notch1-NF-κB activity in the liver were assessed to further verify the in vitro results. Results: Ethanol was shown to induce oxidative stress and steatohepatitis with remarkably elevated Notch1-NF-κB expression in 2E1 cells rather than HepG2 and Neo cells. Notch1 inhibitor was non-toxic in the three cell lines and had a protective effect against markers of ASH. Similarly, chronic alcohol administration in vivo induced alcoholic hepatitis, oxidative stress and elevated Notch1-NF-κB expression in rats, while Notch1 inhibitor attenuated alcoholic liver injury. Conclusion: These findings provide direct in vitro and in vivo evidence that the oxidative stress-induced ASH is mediated by the Notch1-NF-κB signaling pathway, which can be effectively reversed by Notch1 inhibitor.

Blood Ethanol Levels of Nonabstinent Japanese Alcoholic Men in the Morning After Drinking and Their ADH1B and ALDH2 Genotypes

Aims: Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B, rs1229984) and aldehyde dehydrogenase-2 (ALDH2, rs671) affect ethanol (EtOH) metabolism and susceptibility to alcoholism. Methods: We evaluated associations between ADH1B/ALDH2 genotypes and the blood EtOH levels of 805 Japanese alcoholic men in the morning after they had drunk within the previous 34 h. Results: Age-adjusted usual alcohol consumption did not differ according to ADH1B/ALDH2 genotypes. Higher blood EtOH levels persisted for longer periods in the ADH1B*1/*1 carriers (n = 246) than in the ADH1B*2 carriers (n = 559). Blood EtOH levels did not differ by ALDH2 genotype. The blood EtOH levels ≥0.3 mg/ml (criterion for drunk driving in Japanese law) were observed (40% vs. 14–17%, P < 0.0001) in a higher proportion of the ADH1B*1/*1 carriers than of the ADH1B*2 carriers after a 12.1-to-18-h interval since the last drink. Multivariate analyses showed that the EtOH levels heightened by 0.500 mg/ml in the presence of ADH1B*1*1 and by 0.248 mg/ml in the presence of cirrhosis, and lowered by 0.120 mg/ml per 10-year age increase, by 0.087 mg/ml per 10-kg body-weight increase and by 0.673 mg/ml per 10-h interval since the last drink. The odds ratio (95% confidence interval) for an EtOH level ≥0.3 mg/ml was 3.44 (2.34–5.04) in the presence of ADH1B*1/*1, 2.01 (1.28–3.14) in the presence of cirrhosis, 0.59 (0.49–0.71) per 10-year age increase, 0.80 (0.68–0.95) per 10-kg body-weight increase and 0.10 (0.07–0.15) per 10-h interval since the last drink. Conclusion: The longer-than-expected EtOH lingering in the blood of the ADH1B*1/*1 alcoholics may exacerbate alcohol-related problems, including drunk driving.

A GABRA2 Variant Is Associated with Increased Stimulation and ‘High’ Following Alcohol Administration

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Abstract

Aims: Variation in genes encoding GABAA receptor subunits has been implicated in the risk of alcohol dependence (AD). We sought to replicate and extend previous findings of a moderating effect of single nucleotide polymorphisms (SNPs) in GABRA2 (which encodes the GABAA α-2 subunit) on the subjective effects of alcohol by examining SNPs in this and the adjacent GABRG1 gene on chromosome 4. Methods: Fifty-two European-Americans (22 males, 28 light drinkers and 24 heavy drinkers) completed 3 laboratory sessions, during which they drank low-dose, high-dose, or placebo alcohol prior to undergoing periodic assessments of stimulation, sedation and drug enjoyment. We genotyped subjects for three SNPs previously associated with AD: rs279858 in GABRA2, and rs7654165 and rs6447493 in GABRG1. Results: Two SNPs were associated with altered stimulatory effects of alcohol as measured on the Biphasic Alcohol Effects Scale, (rs279858: P = 0.0046; rs6447493: P = 0.0023); both effects were in the opposite direction of previous findings. Carriers of the rs279858 C allele experienced greater stimulation from alcohol. Further inspection of the rs6447493 interaction did not support a pharmacogenetic effect. The effects of rs279858 (but not the other two SNPs) on items from a secondary outcome measure, the Drug Effects Questionnaire (DEQ), were significant. Higher ratings by individuals with the C allele were observed on the DEQ items ‘feel the alcohol effect’ (P < 0.001), ‘like the alcohol effect’ (P < 0.001) and feel ‘high’ (P < 0.001). Conclusion: We did not find that the GABRG1 SNPs rs7654165 and rs6447493 moderated the effects of alcohol. Greater stimulatory and euphoric effects of alcohol in carriers of the rs279858 C allele may, in part, explain the previously reported association of this allele with AD.

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.