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Digestive Diseases (Basel, Switzerland) 2010Alcohol abuse is a common cause of both acute and chronic pancreatitis. There is a wide spectrum of pancreatic manifestations in heavy drinkers from no apparent disease... (Review)
Review
Alcohol abuse is a common cause of both acute and chronic pancreatitis. There is a wide spectrum of pancreatic manifestations in heavy drinkers from no apparent disease in most individuals to acute inflammatory and necrotizing pancreatitis in a minority of individuals with some progressing to chronic pancreatitis characterized by replacement of the gland by fibrosis and chronic inflammation. Both smoking and African-American ethnicity are associated with increased risk of alcoholic pancreatitis. In this review we describe how our recent studies demonstrate that ethanol feeding in rodents causes oxidative stress in the endoplasmic reticulum (ER) of the digestive enzyme synthesizing acinar cell of the exocrine pancreas. This ER stress is attenuated by a robust unfolded protein response (UPR) involving X-box binding protein-1 (XBP1) in the acinar cell. When the UPR activation is prevented by genetic reduction in XBP1, ethanol feeding causes significant pathological responses in the pancreas. These results suggest that the reason most individuals who drink alcohol heavily do not get significant pancreatic disease is because the pancreas mounts an adaptive UPR to attenuate the ER stress that ethanol causes. We hypothesize that disease in the pancreas results when the UPR is insufficiently robust to alleviate the ER stress caused by alcohol abuse.
Topics: Alcoholism; Endoplasmic Reticulum; Humans; Pancreatitis; Smoking; Stress, Physiological; Unfolded Protein Response
PubMed: 21525762
DOI: 10.1159/000327212 -
Journal of Neuroimmune Pharmacology :... Mar 2010There are currently no consistent objective biochemical markers of alcohol abuse and alcoholism. Development of reliable diagnostic biomarkers that permit accurate... (Review)
Review
There are currently no consistent objective biochemical markers of alcohol abuse and alcoholism. Development of reliable diagnostic biomarkers that permit accurate assessment of alcohol intake and patterns of drinking is of prime importance to treatment and research fields. Diagnostic biomarker development in other diseases has demonstrated the utility of both open, systems biology, screening for biomarkers and more rational focused efforts on specific biomolecules or families of biomolecules. Long-term alcohol consumption leads to altered inflammatory cell and adaptive immune responses with associated pathologies and increased incidence of infections. This has led researchers to focus attention on identifying cytokine biomarkers in models of alcohol abuse. Alcohol is known to alter cytokine levels in plasma and a variety of tissues including lung, liver, and very importantly brain. A number of cytokine biomarker candidates have been identified, including: tumor necrosis factor-alpha, interleukin (IL)-1-alpha, IL-1-beta, IL-6, IL-8, IL-12, and monocyte chemoattractant protein-1. This is an emerging and potentially exciting avenue of research in that circulating cytokines may contribute to diagnostic biomarker panels, and a combination of multiple biomarkers may significantly increase the sensitivity and specificity of the biochemical tests aiding reliable and accurate detection of excessive alcohol intake.
Topics: Alcohol-Induced Disorders; Alcoholism; Animals; Biomarkers; Cytokines; Ethanol; Humans; Immune System; Models, Immunological; Nervous System Diseases
PubMed: 20020329
DOI: 10.1007/s11481-009-9185-z -
Pharmacogenomics Dec 2016Transcriptome profiling enables discovery of gene networks that are altered in alcoholic brains. This technique has revealed involvement of the brain's neuroimmune... (Review)
Review
Transcriptome profiling enables discovery of gene networks that are altered in alcoholic brains. This technique has revealed involvement of the brain's neuroimmune system in regulating alcohol abuse and dependence, and has provided potential therapeutic targets. In this review, we discuss Toll-like-receptor pathways, hypothesized to be key players in many stages of the alcohol addiction cycle. The growing appreciation of the neuroimmune system's involvement in alcoholism has also led to consideration of crucial roles for glial cells, including astrocytes and microglia, in the brain's response to alcohol abuse. We discuss current knowledge and hypotheses on the roles that specific neuroimmune cell types may play in addiction. Current strategies for repurposing US FDA-approved drugs for the treatment of alcohol use disorders are also discussed.
Topics: Alcoholism; Animals; Astrocytes; Calcium Signaling; Humans; Microglia; Neuroimmunomodulation; Toll-Like Receptors; Transcriptome
PubMed: 27918243
DOI: 10.2217/pgs-2016-0062 -
Progress in Molecular Biology and... 2019Converging lines of evidence point to a significant role of neuroinflammation in a host of psychiatric conditions, including alcohol use disorder, TBI, and PTSD. A... (Review)
Review
Converging lines of evidence point to a significant role of neuroinflammation in a host of psychiatric conditions, including alcohol use disorder, TBI, and PTSD. A complex interaction of both peripheral and central signaling underlies processes involved in neuroinflammation. Calcineurin is a molecule that sits at the nexus of these processes and has been clearly linked to a number of psychiatric disorders including alcohol use disorder (AUD). Like its role in regulating peripheral immune cells, calcineurin (CN) plays an integral role in processes regulating neuroimmune function and neuroinflammatory processes. Targeting CN or elements of its signaling pathways at critical points may aid in the functional recovery from neuroinflammatory related disorders. In this review we will highlight the role of neuroinflammation and calcineurin signaling in AUD, TBI and stress-induced disorders and discuss recent findings demonstrating a therapeutic effect of immunosuppressant-induced calcineurin inhibition in a pre-clinical model of binge alcohol drinking.
Topics: Alcoholism; Animals; Calcineurin; Humans; Immunosuppressive Agents; Inflammation; Nervous System Diseases
PubMed: 31601401
DOI: 10.1016/bs.pmbts.2019.06.008 -
Anaesthesia May 1980The biochemistry, pharmaco-kinetics, and pathophysiology of alcohol and alcoholism are reviewed and approaches to the clinical management of coma, alcohol withdrawal,... (Review)
Review
The biochemistry, pharmaco-kinetics, and pathophysiology of alcohol and alcoholism are reviewed and approaches to the clinical management of coma, alcohol withdrawal, and anaesthesin are considered.
Topics: Adult; Alcoholism; Anesthesia; Carbohydrate Metabolism; Cardiomyopathy, Alcoholic; Child; Coma; Critical Care; Drug Interactions; Drug Tolerance; Emergencies; Ethanol; Humans; Substance Withdrawal Syndrome; Water-Electrolyte Balance
PubMed: 6994522
DOI: 10.1111/j.1365-2044.1980.tb03825.x -
Pancreatology : Official Journal of the... Jul 2015The majority of those who drink excessive amounts of alcohol do not develop pancreatic disease. One overarching hypothesis is that alcohol abuse requires additional risk... (Review)
Review
The majority of those who drink excessive amounts of alcohol do not develop pancreatic disease. One overarching hypothesis is that alcohol abuse requires additional risk factors, either environmental or genetic, for disease to occur. However, another reason be a result of alcohol-induced activation of adaptive systems that protect the pancreas from the toxic effects of alcohol. We show that mechanisms within the unfolded protein response (UPR) of the endoplasmic reticulum (ER) that can lead to protection of the pancreas from pancreatic diseases with alcohol abuse. The remarkable ability of the pancreas to adapt its machinery to alcohol abuse using UPR systems and continue functioning is the likely reason that pancreatitis from alcohol abuse does not occur in the majority of heavy drinkers. These findings indicate that methods to enhance the protective responses of the UPR can provide opportunities for prevention and treatment of pancreatic diseases.
Topics: Alcoholism; Animals; Endoplasmic Reticulum Stress; Humans; Pancreas; Pancreatitis, Alcoholic; Unfolded Protein Response
PubMed: 25736240
DOI: 10.1016/j.pan.2015.01.011 -
Psychological Services Nov 2022Military deployment is a risk factor for alcohol problems, and postdeployment alcohol problems are more prevalent among part-time reservists than full-time active duty...
Military deployment is a risk factor for alcohol problems, and postdeployment alcohol problems are more prevalent among part-time reservists than full-time active duty service members. However, emerging research suggests that reservists who never experience deployment are also at risk. We examined if never-deployed/activated reserve veterans differed from active duty/deployed veterans in alcohol screening and misuse. Using pooled cross-sectional data from the National Survey on Drug Use and Health (NSDUH; 2015-2019), we estimated the prevalence of past-year self-reported alcohol screening by a health care provider and measured DSM-IV alcohol abuse and alcohol dependence among U.S. veterans aged 18-49 years with at least one health care visit in the past year ( = 4,148). We used regression models to examine for differences in these outcomes between never-deployed/activated reserve veterans and active duty/deployed veterans. Overall, 15% of veterans reported not being screened for alcohol use, despite 1 in 11 meeting DSM-IV criteria for alcohol abuse/dependence. Active duty/deployed veterans were more likely to have been screened for alcohol use than never-deployed/activated reserve veterans ( < .05). However, there was no difference in past-year alcohol abuse ( > .05) or dependence ( > .05) between never-deployed/activated reserve veterans and veterans with a history of active duty service/activation. Never-deployed/activated reserve veterans are less likely to be screened for alcohol use than active duty/deployed veterans, despite no significant difference in meeting alcohol abuse/dependence criteria. Providers may not recognize never-deployed reservists as veterans. We recommend systematic screening for military service history and alcohol use for all veterans, regardless of deployment/active duty service. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Topics: United States; Humans; Veterans; Military Personnel; Alcoholism; Cross-Sectional Studies; Alcohol-Related Disorders; Ethanol
PubMed: 34516202
DOI: 10.1037/ser0000584 -
Alcoholism, Clinical and Experimental... May 2017Advanced alcoholic liver disease (ALD) represents a substantial public health burden, threatening the lives of more than ten million people in the United States.... (Review)
Review
Advanced alcoholic liver disease (ALD) represents a substantial public health burden, threatening the lives of more than ten million people in the United States. Although the direct harmful effects of alcohol in the liver are nearly universally recognized, emerging evidence suggests alcohol also adversely affects other organs such as the intestine, skeletal muscle, adipose tissue, and likely many other tissues. In fact, the extrahepatic effects of alcohol clearly converge to impact the morbidity and mortality associated with chronic alcohol abuse. In the intestine alcohol consumption can profoundly impact both gut barrier function as well as reorganizing intestinal microbial communities. In the skeletal muscle, chronic alcohol consumption promotes sarcopenia by altering protein homeostasis or proteostasis. In parallel, alcohol can impact the normal endocrine and metabolic function of adipose tissue. Collectively, chronic alcohol abuse sustains an interorgan cross talk that provides the multiple hits necessary for progression to end stage liver disease. Here we briefly highlight several recent examples of interorgan cross talk underlying the morbidity and mortality associated with alcohol abuse, and discuss how these recent advances have the potential to impact therapeutic strategies for those suffering with ALD.
Topics: Adipose Tissue; Alcoholism; Animals; Humans; Intestinal Diseases; Liver Diseases, Alcoholic; Muscle, Skeletal
PubMed: 28295407
DOI: 10.1111/acer.13370 -
American Family Physician Apr 2003Ten percent of the population abuses drugs or alcohol, and 20 percent of patients seen by family physicians have substance-abuse problems, excluding tobacco use. These... (Review)
Review
Ten percent of the population abuses drugs or alcohol, and 20 percent of patients seen by family physicians have substance-abuse problems, excluding tobacco use. These patients can be identified by relying on regular screening or a high index of suspicion based on "red flags" that can be noted in various clinical situations. The modified CAGE questionnaire is an excellent screening instrument, but several alternatives are available. The best screening test is one that the physician will routinely use well. Laboratory indicators such as gamma-glutamyl transpeptidase, mean corpuscular volume, and carbohydrate-deficient transferrin are nonspecific but can add to the evidence of alcohol abuse. If problem alcohol use is diagnosed, even brief physician advice can be helpful. If the problem has progressed to addiction, referral to an addiction specialist or treatment center is recommended. Special issues arise in dealing with substance abuse in adolescents, elderly patients, and patients with mental illness, but the family physician can play an important role in recognizing this common problem.
Topics: Age Factors; Alcoholism; Humans; Mass Screening; Physician's Role; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders; Surveys and Questionnaires; Transferrin; gamma-Glutamyltransferase
PubMed: 12722853
DOI: No ID Found -
Alcohol Research : Current Reviews 2022This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as... (Review)
Review
This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as part of the National Institute of Mental Health and later as an independent institute of the National Institutes of Health, NIAAA today is the world's largest funding agency for alcohol research. In addition to its own intramural research program, NIAAA supports the entire spectrum of innovative basic, translational, and clinical research to advance the diagnosis, prevention, and treatment of alcohol use disorder and alcohol-related problems. To celebrate the anniversary, NIAAA hosted a 2-day symposium, "Alcohol Across the Lifespan: 50 Years of Evidence-Based Diagnosis, Prevention, and Treatment Research," devoted to key topics within the field of alcohol research. This article is based on Dr. Sinha's presentation at the event. NIAAA Director George F. Koob, Ph.D., serves as editor of the Festschrift.
Topics: United States; Humans; Alcoholism; Neurobiology; National Institute on Alcohol Abuse and Alcoholism (U.S.); Alcohol Drinking; Alcohol-Related Disorders
PubMed: 36338609
DOI: 10.35946/arcr.v42.1.12