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alcoholism and liver disease in Mexico:Genetic and environmental factors

World Journal of Gastroenterology 2013年第44期19卷 7972-7982页

作者： Sonia Roman Eloy Alfonso Zepeda-Carrillo Laura Eugenia Moreno-Luna Arturo Panduro Department of Molecular Biology in Medicine Civil Hospital of Guadalajara "Fray Antonio Alcalde" and Health Sciences Center University of GuadalajaraGuadalajara Jalisco 44280 Mexico Universidad Autónoma de Nayarit and Hospital Civil Tepic "Antonio González Guevara" Tepic Nayarit 63000 Mexico

alcoholism and cirrhosis,which are two of the most serious health problems worldwide,have a broad spectrum of clinical *** diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each *** contrast to other regions around the world,Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol *** has a unique history of alcohol consumption that is linked to profound anthropological and social *** Mexican population has an admixture genome inherited from different races,Caucasian,Amerindian and African,with a heterogeneous distribution within the ***,genes related to alcohol addiction,such as dopamine receptor D2 in the brain,or liver alcoholmetabolizing enzymes,such as alcohol dehydrogenase classⅠpolypeptide B,cytochrome P450 2E1 and aldehyde dehydrogenase class 2,may vary from one individual to ***,they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver ***,in this era of genomics,personalized medicine will benefit patients if it is directed according to individual or population-based *** association studies will be required to establish novel strategies for the prevention,care and treatment of liver disease in Mexico and worldwide.

关键词： Alcohol Genes alcoholism Alcohol dependence Alcohol addiction Alcohol abuse Alcoholic liver cirrhosis Anthropology

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alcoholism: A systemic proinflammatory condition

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World Journal of Gastroenterology 2014年第40期20卷 14660-14671页

作者： Emilio González-Reimers Francisco Santolaria-Fernández María Candelaria Martín-González Camino María Fernández-Rodríguez Geraldine Quintero-Platt Servicio de Medicina Interna Hospital Universitario de Canarias Universidad de La Laguna Tenerife 38320 Canary Islands Spain

Excessive ethanol consumption affects virtually any organ,both by indirect and direct *** 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 *** 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 *** oxygen species(ROS)that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of *** effects of this increased cytokine secretion and ROS generation lie far beyond liver *** addition to the classic consequences of endotoxemia associated with liver cirrhosis that weredescribed 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 *** effects are even seen in alcoholics without significant liver ***,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 *** 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.

关键词： alcoholism Cytokines Brain Bone Muscle Oxidative damage Atherosclerosis Sepsis Lung Chronic pancreatitis Alcoholic liver disease

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Electroencephalogram (EEG) Brain Signals to Detect alcoholism Based on Deep Learning

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Computers, Materials & Continua 2021年第6期67卷 3329-3348页

作者： Emad-ul-Haq Qazi Muhammad Hussain Hatim A.AboAlsamh Visual Computing Lab Department of Computer ScienceCollege of Computer and Information SciencesKing Saud UniversityRiyadh11543Saudi Arabia

The detection of alcoholism is of great importance due to its effects on individuals and *** alcoholism detection system(AADS)based on electroencephalogram(EEG)signals is effective,but the design of a robust AADS is a challenging ***’current designs are based on conventional,hand-engineered methods and restricted *** by the excellent deep learning(DL)success in many recognition tasks,we implement an AAD system based on EEG signals using DL.A DL model requires huge number of learnable parameters and also needs a large dataset of EEG signals for training which is not easy to obtain for the AAD *** order to solve this problem,we propose a multi-channel Pyramidal neural convolutional(MP-CNN)network that requires a less number of learnable *** the deep CNN model,we build an AAD system to detect from EEG signal segments whether the subject is alcoholic or *** validate the robustness and effectiveness of proposed AADS using KDD,a benchmark dataset for alcoholism detection *** order to find the brain region that contributes significant role in AAD,we investigated the effects of selected 19 EEG channels(SC-19),those from the whole brain(ALL-61),and 05 brain regions,i.e.,TEMP,OCCIP,CENT,FRONT,and *** results show that SC-19 contributes significant role in AAD with the accuracy of 100%.The comparison reveals that the state-of-the-art systems are outperformed by the *** proposed AADS will be useful in medical diagnosis research and health care systems.

关键词： Electroencephalogram convolutional neural network deep learning alcoholism

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Threshold dynamics of a multi-group SEAR alcoholism model with public health education

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International Journal of Biomathematics 2019年第3期12卷 39-62页

作者： Shuang-Hong Ma Hai-Feng Huo Hong Xiang College of Electrical and Information Engineering Lanzhou University of Technology Lanzhou 730050 P. R. China Institute of Applied Mathematics Lanzhou University of Technology Lanzhou 730050 P. R. China

In this paper, we investigate the threshold dynamics of a multi-group SEAR alcoholism epidemic model with public health education. The multi-group model allows us to describe interactions both within-group and inter-group separately. We prove that the basic reproduction number R0 plays the role of a threshold for the long-time behavior of the model. The alcohol-free equilibrium P0 of the model is globally asymptotically stable if R0≤1,while the alcohol-present equilibrium P* exists uniquely and is globally asymptotically stable if R0>*** the proofs of main results, we use the classical method of Lyapunov functions and apply subtle grouping technique in estimating the derivatives of Lyapunov functions guided by graph theory. Our results expand the previous results which have been obtained in single-group models. Sensitivity analysis and numerical simulations are also performed to illustrate our results.

关键词： Multi-group model alcoholism graph-theoretic approach global stability

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Novel strategies to mine alcoholism-related haplotypes and genes by combining existing knowledge framework

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Science China(Life Sciences) 2009年第2期52卷 163-172页

作者： ZHANG RuiJie1, LI Xia1,2, JIANG YongShuai1, LIU GuiYou1, LI ChuanXing1, ZHANG Fan1, XIAO Yun1 & GONG BinSheng1 1 Department of Bioinformatics, Harbin Medical University, Harbin 150086, China 2 Biomedical Engineering Institute of CUMS, Beijing 100054, China 1. Department of Bioinformatics Harbin Medical University Harbin 150086 China 2. Biomedical Engineering Institute of CUMS Beijing 100054 China

High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods (Confidence Intervals, Four Gamete Tests, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the alco- holism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism most possibly on chromosome 1~22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism. We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not only can handle the SNP data easily, but also can locate the disease-related genes pre- cisely by combining our novel strategies of mining alcoholism-related haplotypes and genes with ex- isting knowledge framework.

关键词： haplotype block alcoholism gene functional annotation gene location linkage disequilibrium

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Phosphodiesterases:novel targets for treatment of alcoholism

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中国药理学与毒理学杂志 2017年第5期31卷 454-455页

作者： LIU Xin WEN Rui-ting GONG Mei-fang XU Ying Nicolas GRAHAME XU Jiang-ping LIANG Jian-hui Marco CONTI 张汉霆 Institute of Pharmacology Taishan Medical University Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology Blanchette Rockefeller Neurosciences InstituteWest Virginia University Health Sciences Center Department of Molecular and Cellular Pharmacology School of Pharmaceutical SciencesPeking University Department of Pharmacology School of Pharmaceutical SciencesSouthern Medical University Department of Pharmaceutical Sciences State University of New York at Buffalo Department of Psychology Indiana University-Purdue University Indianapolis Center for Reproductive Sciences Department of ObstetricsGynecology and Reproductive SciencesUniversity of California 泰山医学院药理学研究所泰山医学院药学院美国西弗吉尼亚大学医学院中国旅美科技协会西弗吉尼亚分会美国西弗吉尼亚华人协会

OBJECTIVE alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in ***(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol ***,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by *** The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcohol

关键词： phosphodiesterase alcohol drinking alcoholism anxiety depression rodents

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Effect of acute alcoholism on hepatic enzymes and oxidation/antioxidation in rats

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Hepatobiliary & Pancreatic Diseases International 2004年第2期3卷 241-244页

作者： You-Ming Li, Shao-Hua Chen, Chao-Hui Yu, Yu Zhang and Gen-Yun Xu Hangzhou, China Department of Digestive Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003 . Chi- na Department of Digestive Medicine First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: Around the world more and more people suffer from acute alcoholism. The purpose of this study was to determine hepatic enzymes and oxidation/antioxidation in rats with acute alcoholism. METHODS: Rats were randomly divided into three groups; control, low-dose alcohol, and high-dose alcohol. Each al- cohol group ( n = 12) was intravenously infused with etha- nol at a dose of 0.3 or 0.7 g/kg body weight respectively. The control group (n =11) was intravenously infused with normal saline at a dose of 0.5 g/kg body weight. Blood was collected for detection of hepatic enzymes and index of oxidation/antioxidation. RESULTS: The ratio of AST to ALT was 2.44±0.46, 2.57± 0.60 and 3.03 ±0.46 in the three groups, and the difference was significant between the control and high-dose alcohol groups (P^0.05). No significant changes were observed in the levels of serum alanine aminotransferase (ALT), aspar- tate aminotransferase (AST), total protein (Tp), albumin (Alb), alkaline phosphatase (ALP), cholinesterase (ChE), total bilirubin (TB), C-reactive protein (CRP) and amy- lase. The levels of serum nitric oxide (NO) in the 3 groups were 39.2 ±73.25 mol/L, 42.30 ±4.60 mol/L and 47.86± 4.66 mol/L, and significant difference was seen between the control group and the high-dose alcohol group (P < 0.01). No significant difference was found in the levels of serum superoxide dismutase (SOD), glutathione (GSH), malondiethylaldehyde (MDA), and CRP in the 3 groups. CONCLUSION: The ratio of AST to ALT appears to be a useful index for acute alcohol intoxication. NO is involved in the mechanism of acute alcohol intoxication.

关键词： alcoholism infusion nitric oxide oxidation/antioxidation animal model hepatic enzyme

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alcoholism and critical illness: A review

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World Journal of Critical Care Medicine 2016年第1期5卷 27-35页

作者： Ashish Jitendra Mehta Division of Pulmonary Critical Care Medicine Department of Medicine Atlanta VA Medical Center Emory University School of Medicine

Alcohol is the most commonly used and abused drug in the world, and alcohol use disorders pose a tremendousburden to healthcare systems around the world. The lifetime prevalence of alcohol abuse in the United States is estimated to be around 18%, and the economic consequences of these disorders are staggering. Studies on hospitalized patients demonstrate that about one in four patients admitted to critical care units will have alcohol-related issues, and unhealthy alcohol consumption is responsible for numerous clinical problems encountered in intensive care unit(ICU) settings. Patients with alcohol use disorders are not only predisposed to developing withdrawal syndromes and other conditions that often require intensive care, they also experience a considerably higher rate of complications, longer ICU and hospital length of stay, greater resource utilization, and significantly increased mortality compared to similar critically ill patients who do not abuse alcohol. Specific disorders seen in the critical care setting that are impacted by alcohol abuse include delirium, pneumonia, acute respiratory distress syndrome, sepsis, gastrointestinal hemorrhage, trauma, and burn injuries. Despite the substantial burden of alcoholinduced disease in these settings, critical care providers often fail to identify individuals with alcohol use disorders, which can have significant implications for this vulnerable population and delay important clinical interventions.

关键词： alcoholism Alcohol withdrawal delirium Alcohol-related disorders critical illness Intensive care Pneumonia Sepsis Acute respiratory distress syndrome Delirium Trauma

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Genome-wide differences in hepatitis C-vs alcoholism-associated hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第11期14卷 1749-1758页

作者： Céline Derambure Cédric Coulouarn Frédérique Caillot Romain Daveau Martine Hiron Michel Scotte Arnaud Franois Celia Duclos Odile Goria Marie Gueudin Catherine Cavard Benoit Terris Maryvonne Daveau Jean-Philippe Salier Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides Facultéde Médecine-PharmacieRouenFrance Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides Facultéde Médecine-PharmacieRouenFrance Service de Chirurgie Générale et DigestiveCentre Hospitalier UniversitaireRouenFrance Département de Pathologie Centre Hospitalier UniversitaireRouenFrance Inserm Unité519 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides Facultéde Médecine-PharmacieRouenFrance Service d'Hépato-gastro-enterologieCentre Hospitalier UniversitaireRouenFrance Laboratoire de Virologie and UPRES EA 2646 Centre Hospitalier UniversitaireRouenFrance Inserm Unité567 CNRS UMR 8104 UniversitéParis 5Département GDPMInstitut CochinParis France

AIM:To look at a comprehensive picture of etiology- dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS:With a liver-oriented microarray,transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism,12;hepatitis C,10)and 5 *** or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set(12+10) and a test set(6+7). RESULTS:A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism)or-2(hepatitis C)and ontology indicated a predominant inflammatory response(alcoholism)or changes in cell cycle regulation,transcription factors and interferon responsiveness(hepatitis C).A stringent selection of 23 transcripts whose differences betweenetiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding *** 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION:Etiology-specific abnormalities(chromo- some preference;differences in transcriptomes and related functions)have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis *** may open novel avenues for differential therapies in this disease.

关键词： alcoholism Chromosome Cirrhosis Hepatitis C Transcriptomes Protein function

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Evaluation of embryonic alcoholism from auditory event-related potential in fetal rats

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Chinese Medical Journal 2004年第9期117卷 1422-1424页

作者：梁勇王正敏屈卫东 Department of Otorhinolaryngology Nanfang Hospital First Military Medical University Guangzhou 510515 China Department of Otorhinolaryngology Eye & ENT Hospital Fudan University Shanghai 200031 China

Auditory event-related potential (AERP) is a kind of electroencephalography that measures the responses of perception, memory and judgement to special acoustic stimulation in the auditory cortex. AERP can be recorded with not only active but also passive mode. The active and passive recording modes of AERP have been shown a possible application in animals. Alcohol is a substance that can markedly affect the conscious reaction of human. Recently, AERP has been applied to study the effects of alcohol on the auditory centers of the brain. Some reports have shown dose-dependent differences in latency, amplitude, responsibility and waveform of AERP between persons who have and have not take in alcohol. The epidemiological investigations show that the central nervous function of the offspring of alcohol users might be also affected. Because the clinic research is limited by certain factors, several animal models have been applied to examine the influences of alcohol on consciousness with AERP. In the present study, young rats were exposed to alcohol during fetal development and AERP as indicator was recorded to monitor the central auditory function, and its mechanisms and characteristics of effects of the fetal alcoholism on auditory center function in rats were analyzed and discussed.

关键词： alcoholism auditory event-related potential embryo

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