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BMJ (Clinical Research Ed.) Sep 2018
Topics: Alcohol Drinking; Alcoholic Intoxication; Alcoholism; Central Nervous System; Cost of Illness; England; Ethanol; Humans; Public Health; Substance-Related Disorders
PubMed: 30237231
DOI: 10.1136/bmj.k3944 -
World Journal of Gastroenterology Oct 2014Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the... (Review)
Review
Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.
Topics: Alcohol Drinking; Alcoholism; Animals; Cytokines; Ethanol; Humans; Inflammation; Inflammation Mediators; Liver; Liver Diseases, Alcoholic; Oxidative Stress; Prognosis; Reactive Oxygen Species; Risk Assessment; Risk Factors
PubMed: 25356029
DOI: 10.3748/wjg.v20.i40.14660 -
Addiction (Abingdon, England) Nov 2018There is consensus that best clinical practice for dual diagnosis (DD) is integrated mental health and substance use treatment augmented with Alcoholics Anonymous (AA)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There is consensus that best clinical practice for dual diagnosis (DD) is integrated mental health and substance use treatment augmented with Alcoholics Anonymous (AA) attendance. This is the first quantitative review of the direction and magnitude of the association between AA attendance and alcohol abstinence for DD patients.
METHOD
A systematic literature search (1993-2017) identified 22 studies yielding 24 effect sizes that met our inclusion criteria (8075 patients). Inverse-variance weighting of correlation coefficients (r) was used to aggregate sample-level findings and study aims were addressed using random- and mixed-effect models. Sensitivity and publication bias analyses were conducted to assess the likelihood of bias in the overall estimate of AA-related benefit.
RESULTS
AA exposure and abstinence for DD patients were associated significantly and positively [r = 0.249; 95% confidence interval (CI) = 0.203-0.293; tau = 0.097). There was also significant heterogeneity in the distribution of effect sizes and high between-sample variance (I = 74.6, P < 0.001). Subgroup analyses indicated that the magnitude of AA-related benefit did not differ between 6- (k = 7) and 12- (k = 12) month follow-up (Q = 0.068, P = 0.794), type of treatment received (in-patient k = 9; intensive out-patient, out-patient, community k = 15; Q = 2.057, P = 0.152), and whether a majority of patients in a sample had (k = 11) or did not have (k = 13) major depression (Q = 0.563, P = 0.453). Sensitivity analyses indicated that the overall meta-analytical estimate of AA benefit was not impacted adversely or substantively by pooling randomized controlled trial (RCT) and observational samples (Q = 0.763, P = 0.382), pooling count, binary and ordinal-based AA (Q = 0.023, P = 0.879) and outcome data (Q = 1.906, P = 0.167) and reversing direction of correlations extracted from studies (Q = 0.006, P = 0.937). No support was found for publication bias.
CONCLUSIONS
Clinical referral of dual diagnosis patients to Alcoholics Anonymous is common and, in many cases, dual diagnosis patients who attend Alcoholics Anonymous will report higher rates of alcohol abstinence relative to dual diagnosis patients who do not attend Alcoholics Anonymous.
Topics: Alcohol Abstinence; Alcoholics Anonymous; Alcoholism; Anxiety Disorders; Depressive Disorder, Major; Diagnosis, Dual (Psychiatry); Humans; Stress Disorders, Post-Traumatic
PubMed: 29845709
DOI: 10.1111/add.14268 -
Current Pharmaceutical Design 2022A growing body of evidence indicates that repeated alcohol exposure or withdrawal from alcohol can result in persistent molecular and cellular adaptations. One molecular... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
A growing body of evidence indicates that repeated alcohol exposure or withdrawal from alcohol can result in persistent molecular and cellular adaptations. One molecular adaptation that occurs is the regulation of gene expression, which is believed to lead to functional alterations that characterize addiction. MicroRNAs (miRs) have been recently identified as master regulators of gene expression through posttranscriptional regulation. The aim of this meta-analytic review was to evaluate the regulatory forms of miRs during alcoholism.
METHODS
We used several databases such as PubMed, Scopus, and Web of Science without limitations on publication time. All studies were analyzed by Comprehensive Meta-Analysis software.
RESULTS AND DISCUSSION
Six clinical papers with 243 alcoholic patients and 162 controls were included. In this study, 1680 articles were initially reviewed and eventually, six clinical studies were included in the metaanalysis. The results of the meta-analysis showed that according to the random model, the difference between the upregulation and downregulation of central addiction targets was statistically significant, indicating that most dopamine- or gamma-aminobutyric acid receptor subunit (GABA)-related miRs are upregulated in alcoholics (P: 0.00, CI: 0.149-0.439).
CONCLUSION
This study strongly suggests that dopamine- or GABA-related miRs were mostly upregulated in alcoholism. Our findings revealed that about 9% of miRs were downregulated in alcoholism, including miR- 567, miR-126, miR-1, miR-432, and miR-153. To identify other or specific miRs as potential biomarkers in alcoholics, large-scale studies and more clinical work are required.
Topics: Alcoholism; Dopamine; Down-Regulation; Humans; MicroRNAs; gamma-Aminobutyric Acid
PubMed: 35619318
DOI: 10.2174/1381612828666220520112928 -
International Journal of Molecular... Feb 2023Myostatin acts as a negative regulator of muscle growth. Its effect on fat mass is subject to debate. Among alcoholics, there is a high prevalence of muscle atrophy, and...
Myostatin acts as a negative regulator of muscle growth. Its effect on fat mass is subject to debate. Among alcoholics, there is a high prevalence of muscle atrophy, and increased fat deposition has been also described in these patients. Myostatin could be involved in these alterations, but its relationships with body composition have been scarcely studied in alcoholic patients. To analyze the behavior of myostatin among alcoholics and its relationship with alcohol intake, liver function, and body composition. We investigated serum myostatin in 59 male patients and 18 controls. Patients were all heavy drinkers admitted with organic complications related to excessive ethanol ingestion. Densitometry analysis was used to assess body composition in 46 patients. Handgrip was assessed in 51 patients. Patients showed lower myostatin values than controls (Z = 3.80; < 0.001). There was a significant relationship between myostatin and fat at the right leg (ρ = 0.32; = 0.028), left leg (ρ = 0.32; = 0.028), trunk (ρ = 0.31, = 0.038), total fat proport ion (ρ = 0.33, = 0.026), and gynecoid fat distribution (ρ = 0.40, = 0.006) but not with lean mass (total lean ρ = 0.07; = 0.63; trunk lean ρ = 0.03; = 0.85; lower limbs ρ = 0.08; = 0.58; upper limbs ρ = 0.04 = 0.82; android ρ = 0.02; = 0.88, or gynoid lean mass ρ = 0.20; = 0.19). In total, 80.43% of patients showed at least one criterion of osteosarcopenic adiposity (OSA). Myostatin was related to OSA obesity. We also observed higher myostatin values among patients with body mass index > 30 kg/m. Serum myostatin was lower among excessive drinkers, and it was related to increased fat deposition among these patients but not to lean mass, handgrip, or bone mineral density.
Topics: Humans; Male; Alcoholism; Body Composition; Hand Strength; Myostatin; Obesity
PubMed: 36769301
DOI: 10.3390/ijms24032981 -
Current Drug Abuse Reviews 2015Ethanol is the most abused psychoactive substance. Accordingly to World Health Organization ethanol ranks among the top five risk factors for disease, disability and... (Review)
Review
Ethanol is the most abused psychoactive substance. Accordingly to World Health Organization ethanol ranks among the top five risk factors for disease, disability and death (3.3 million/year) throughout the world. This manuscript highlights and critically analyses clinical and forensic signs related to hepatoxicity of ethanol that may lead to suspected of abuse. Namely, steatosis, jaundice, cirrhosis, hemorrhoids, esophageal varices caput medusae, ascites, petechiae, ecchymoses, splenomegaly, hemochromatosis, xanthelasma, nutritional deficiency, testicular atrophy, gynecomastia and dilated congestive cardiomyopathy are discussed and related to the toxic mechanism of ethanol.
Topics: Alcoholism; Ethanol; Global Health; Humans; Liver Diseases, Alcoholic
PubMed: 26452450
DOI: 10.2174/1874473708666150916113352 -
Alcoholism, Clinical and Experimental... Apr 2021Recent studies in alcohol use disorders (AUDs) have demonstrated some connections between carnitine metabolism and the pathophysiology of the disease. In this scoping... (Review)
Review
Recent studies in alcohol use disorders (AUDs) have demonstrated some connections between carnitine metabolism and the pathophysiology of the disease. In this scoping review, we aimed to collate and examine existing research available on carnitine metabolism and AUDs and develop hypotheses surrounding the role carnitine may play in AUD. A scoping review method was used to search electronic databases in September 2019. The database search terms used included "alcohol, alcoholism, alcohol abuse, alcohol consumption, alcohol drinking patterns, alcohol-induced disorders, alcoholic intoxication, alcohol-related disorders, binge drinking, Wernicke encephalopathy, acylcarnitine, acetyl-l-carnitine, acetylcarnitine, carnitine and palmitoylcarnitine." The inclusion criteria included English language, human-based, AUD diagnosis and measured blood or tissue carnitine or used carnitine as a treatment. Of 586 studies that were identified and screened, 65 underwent abstract review, and 41 were fully reviewed. Eighteen studies were ultimately included for analysis. Data were summarized in an electronic data extraction form. We found that there is limited literature available. Alcohol use appears to impact carnitine metabolism, most clearly in the setting of alcoholic cirrhosis. Six studies found carnitine to be increased in AUD, of which 5 were conducted in patients with alcoholic cirrhosis. Only 3 placebo-controlled trials were identified and provide some support for the use of carnitine in AUD to decrease cravings, anhedonia, and withdrawal and improve cognition. The increase in plasma carnitine in alcoholic cirrhosis may be related to disordered fatty acid metabolism and oxidative stress that occurs in AUD. The multiple possible therapeutic effects carnitine could have on ethanol metabolism and the early evidence available for carnitine supplementation as a treatment for AUD provide a foundation for future randomized control trials of carnitine for treating AUD.
Topics: Alcoholism; Carnitine; Dietary Supplements; Humans
PubMed: 33576525
DOI: 10.1111/acer.14568 -
CNS Neuroscience & Therapeutics May 2023Electroencephalography (EEG)-based electrophysiological techniques have made progress in diagnosing and treating alcohol dependence in recent years. (Review)
Review
BACKGROUND
Electroencephalography (EEG)-based electrophysiological techniques have made progress in diagnosing and treating alcohol dependence in recent years.
AIMS
The article reviews the latest literature in this field.
MATERIALS AND METHODS
Alcohol dependence, which is common and prone to relapsing, poses a serious threat to individuals, families, and society. At present, the objective detection methods for alcohol dependence in clinic are not enough. As electrophysiological techniques developed in psychiatry, some researches on EEG-based monitoring methods are of great significance in the diagnosis and treatment of alcohol dependence.
DISCUSSION
As electrophysiological techniques developed in psychiatry, some researches on EEG-based monitoring methods such as resting electroencephalography (REEG), event-related potentials (ERP), event-related oscillations (ERO), and polysomnography (PSG), was reported.
CONCLUSION
In this paper, the status of electrophysiological researches on EEG in alcoholics are reviewed in detail.
Topics: Humans; Alcoholism; Electroencephalography; Evoked Potentials
PubMed: 36890659
DOI: 10.1111/cns.14138 -
CNS Spectrums Aug 2021Brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and in the protection against oxidative damage and neuronal apoptosis. After exercise, there is an...
BACKGROUND
Brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and in the protection against oxidative damage and neuronal apoptosis. After exercise, there is an increased expression of this myokine, especially in skeletal muscle and brain. Low BDNF levels have been described in neurodegenerative diseases. Alcoholics show both muscle atrophy and brain atrophy. Thus, this study was performed in order to analyze serum BDNF levels among alcoholics and their associations with brain atrophy and muscle strength.
METHODS
Serum BDNF values were determined to 82 male alcoholics and 27 age-matched controls, and compared with handgrip strength, with the presence of brain atrophy, assessed by computed tomography, and with the intensity of alcoholism and liver function derangement.
RESULTS
BDNF levels and handgrip strength were significantly lower among patients. Handgrip strength was correlated with BDNF values, both in the whole population and in alcoholics, especially in patients over 59 years of age. BDNF was poorly related to liver dysfunction but showed no relationship with brain atrophy or age.
CONCLUSION
Chronic alcoholics show decreased BDNF serum levels that are related to muscle function impairment rather than to age, brain atrophy, liver dysfunction, or the amount of ethanol consumed.
Topics: Aged; Alcoholism; Atrophy; Brain; Brain-Derived Neurotrophic Factor; Humans; Male; Middle Aged; Tomography, X-Ray Computed
PubMed: 32423492
DOI: 10.1017/S1092852920001431 -
Advances in Experimental Medicine and... 2015The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a phosphatidylinositol (PtdIns) phosphatase that regulates Akt activation via... (Review)
Review
The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a phosphatidylinositol (PtdIns) phosphatase that regulates Akt activation via PtdIns 3 kinase. Changes in PTEN expression and/or activity have been identified in a variety of chronic hepatocellular disorders including obesity, NAFLD, NASH, and alcoholism. In cancer biology, PTEN is frequently mutated or deleted in a wide variety of tumors. Mutations, decreased promoter activity, and decreased expression in PTEN are frequently identified in patients with hepatocellular carcinoma. While the majority of research on PTEN concerns obesity and NASH, PTEN clearly has a role in hepatic insulin sensitivity and in the development of steatosis during chronic alcoholism. Yet, in chronic alcoholics and HCC, very little is known concerning PTEN mutation/deletion or low PTEN expression. This review is focused on an overview of the current knowledge on molecular mechanisms of dysregulation of PTEN expression/activity in the liver and their relationship to development of ethanol-induced hepatocellular damage and cancer.
Topics: Alcoholism; Animals; Carcinoma, Hepatocellular; Humans; Liver; Liver Diseases, Alcoholic; Liver Neoplasms; PTEN Phosphohydrolase; Protein Processing, Post-Translational
PubMed: 25427907
DOI: 10.1007/978-3-319-09614-8_10