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SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Acta Pharmaceutica Sinica B 2022年第8期12卷 3281-3297页

作者： Baeksun Kim Sung Hyun Tag Eunjoo Nam Suji Ham Sujin Ahn Juhwan Kim Doo-Wan Cho Sangjoon Lee Young-Su Yang Seung Eun Lee Yong Sik Kim Il-Joo Cho Kwang Pyo Kim Su-Cheol Han Heh-In Im Convergence Research Center for Diagnosis Treatment and Care System of Dementia(DTC)Korea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea Division of Bio-Medical Science&Technology KIST SchoolKorea University of Science and Technology(UST)Seoul 02792Republic of Korea Center for Neuroscience KISTSeoul 02792Republic of Korea Animal Model Research Center Jeonbuk Department of Inhalation ResearchKorea Institute of Toxicology(KIT)Korea Research Institute of Chemical Technology(KRICT)Jeongeup 56212Republic of Korea Research Animal Resource Center KISTSeoul 02792Republic of Korea Department of Pharmacology Seoul National University College of MedicineSeoul 03080Republic of Korea Center for BioMicrosystems KISTSeoul 02792Republic of Korea Department of Applied Chemistry Kyung Hee UniversityGyeonggi-do 17104Republic of Korea

abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine(MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR,LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.

关键词： Methamphetamine abstinence Withdrawal Striatum miR-137 SYNCRIP Biomarker Behavior

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Alcohol liver disease: A review of current therapeutic approaches to achieve long-term abstinence

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World Journal of Gastroenterology 2015年第28期21卷 8516-8526页

作者： María Luisa Gutiérrez García Sara Blasco-Algora Conrado M Fernández-Rodríguez Service of Gastroenterology Hospital Universitario Fundación

Harmful alcohol drinking may lead to significant damage on any organ or system of the body.Alcoholic liver disease(ALD) is the most prevalent cause of advanced liver disease in Europe.In ALD,only alcohol abstinence was associated with a better long-term survival.Therefore,current effective therapeutic strategy should be oriented towards achieving alcohol abstinence or a significant reduction in alcohol consumption.Screening all primary care patients to detect those cases with alcohol abuse has been proposed as population-wide preventive intervention in primary care.It has been suggested that in patients with mild alcohol use disorder the best approach is brief intervention in the primary care setting with the ultimate goal being abstinence,whereas patients with moderate-to-severe alcohol use disorder must be referred to specialized care where detoxification and medical treatment of alcohol dependence must be undertaken.

关键词： Alcohol use disorders Alcoholic liver disease Alcohol abstinence Alcohol withdrawal syndrome Alcohol dependence

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abstinence Design

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Journal of Educational Theory and Management 2020年第1期4卷 56-60页

作者： Qiang Wu Wuyi University WuyishanFujian354300China

abstinence design is a design that helps people to get rid of bad habits or hobbies for self-management purposes,which seems to limit people’s“freedom”and is contrary to the idea of designing“people-oriented”.However,it is not difficult to find out that only the design that can resist“human desire”is the design of“true freedom.”abstinence design has the idea of green design and minimalist design.It is more in line with the Chinese culture and philosophy,and has positive significance for the improvement of the quality of individuals and even the whole nation.In designing abstinence products,in addition to the degree of desire and need to be treated differently,more guidance on design methods,such as fun,gamification,peak-end principle,etc.,is required to enable users to achieve self-management more effectively.

关键词： abstinence design Freedom Design method

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Personal Accounts of Mothers’ Use of Social Media to Support abstinence from Alcohol

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Journal of Biosciences and Medicines 2017年第12期5卷 67-80页

作者： Suzanne McGarva Tony Machin Northumbria University Newcastle UK

Alcohol consumption by professional educated women and mothers is rising. Drinking alcohol in the home is, for many, becoming a normalised and daily ritual. Previous research focuses on causality, risk factors and health related damage. Few studies focus on mothers of school age children specifically or why some mothers pursue and sustain alcohol free lives. The role of social media in enacting and sustaining abstinence is under researched, as are other factors important for this group in remaining abstinent. Aims: This qualitative study explored the reasons why mothers drank alcohol, and factors contributing to their decision to become alcohol free. It also explored the value and utility of social media in the form of a specific website aimed at providing support in abstinence. Methods: Six UK mothers with school age children who had become abstinent after previously drinking over official limits were recruited via social network website and interviewed. Transcripts were analysed thematically and inductive themes emerged. Results: Participants used alcohol to self-medicate, as a reward/relaxation strategy and because it was a normal part of their professional and daily lives. Reported reasons for abstinence included the negative effects alcohol had upon lives, inability to moderate/drink within guidelines and “trigger” events. Participants reported that their use of social media was inspirational, giving them a platform to share stories and help others and was preferred to traditional support. The use of social media in this way represented a supportive community and assisted vigilance toward the danger of relapse. Positive parenting identity, alternatives to alcohol, abstinence rewards and support from abstinent others were all factors in sustaining abstinence. Conclusions: Health professionals should recognise this hidden and hard to reach group and the potential efficacy of social media in assisting recovery from alcohol related issues.

关键词： Alcohol Drinking Professional Women/Mothers Support Social Media abstinence

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Liver transplantation and alcoholic liver disease:History,controversies,and considerations

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World Journal of Gastroenterology 2018年第26期24卷 2785-2805页

作者： Claudio Augusto Marroni Alfeu de Medeiros Fleck Jr Sabrina Alves Fernandes Lucas Homercher Galant Marcos Mucenic Mario Henrique de Mattos Meine Guilherme Mariante-Neto Ajacio Bandeira de Mello Brandao Graduate Program in Medicine:Hepatology Universidade Federal de Ciências da Saúde de Porto Alegre(UFCSPA)Porto Alegre 90430-080RSBrazil Liver Transplant Adult Group Irmandade da Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90035-072RSBrazil Nutrition at the Centro Universitário Metodista(IPA) Porto Alegre 90420-060RSBrazil

Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease(ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation(LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a "self-inflicted disease". One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this "6-mo rule" is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps t

关键词： Alcoholic liver disease Alcoholic hepatitis Alcoholic cirrhosis Alcoholism Liver transplantation Alcoholic recurrence Controversies Alcoholic abstinence Relapse Selection criteria

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Understanding that Addiction Is a Brain Disorder Offers Help and Hope

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Health 2022年第6期14卷 684-695页

作者： Kenneth Blum Abdalla Bowirrat David Baron Rajendra D. Badgaiyan Panayotis K. Thanos Igor Elman Eric R. Braverman Mark S. Gold Division of Addiction Research & Education Center for Psychiatry Medicine & Primary Care (Office of the Provost) Western University Health Sciences Pomona USA Department of Molecular Biology and Adelson School of Medicine Ariel University Ariel Israel Department of Psychiatry South Texas Veteran Health Care System Audie L. Murphy Memorial VA Hospital and Long School of Medicine University of Texas Health Science Center San Antonio USA Department of Psychiatry MT. Sinai School of Medicine New York USA Department of Psychology & Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA) Research Institute on Addictions University at Buffalo Buffalo USA Department of Psychiatry Harvard School of Medicine Cambridge USA Division of Personalized Medicine The Kenneth Blum Behavioral & Neurogenetic Institute (Division of iVitalize Inc.) Austin USA Department of Psychiatry Washington University School of Medicine St. Louis USA

We refute the controversial statement that addiction is not a brain disorder. Extensive peer-reviewed studies support the underlying neurobiological and neurogenetic basis of addiction’s “disease model”. In the 70s and 80s, a few clinical scientists suggested that it is possible to use behavioral training to teach controlled drinking. However, this controversial model failed drastically and increased labeling and stigmatization. Additionally, it was unhelpful in the search for treatment. Instead, we assert that addiction is a neuropsychiatric disorder characterized by a recurring desire to continue taking substances despite harmful physical and mental consequences. Work from our laboratory in 1995 supported the Reward Deficiency Syndrome (RDS) concept based on a common neurogenetic mechanism (hypodopaminergia) that underlies all substance and non-substance addictions. Non-substance addictions include behaviors like pathological gambling, internet addiction, and mobile phone addiction. Certain impulsive and compulsive behaviors or the acute intake of psychoactive substances result in heightened dopaminergic activity, while the opposite, hypodopaminergia, occurs following chronic abuse. Patients with Substance Use Disorder (SUD) can have a genetic predisposition compounded by stress or other epigenetic insults that can impact recovery. Relapse will occur post-short-term recovery if dopaminergic dysfunction remains untreated. Addiction, a brain disorder, requires treatment with DNA-directed pro-dopamine regulation and rehabilitation.

关键词： Reward Deficiency Syndrome abstinence Controlled Drinking Neurogenetic Brain Disorder

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Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis

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World Journal of Gastroenterology 2015年第16期21卷 4975-4985页

作者： Fátima Higuera-de la Tijera Alfredo I Servín-Caamano Aurora E Serralde-Zúniga Javier Cruz-Herrera Eduardo Pérez-Torres Juan M Abdo-Francis Francisco Salas-Gordillo JoséL Pérez-Hernández Liver Clinic Gastroenterology DepartmentHospital General de MéxicoDr.Eduardo LiceagaMexico City 06720Mexico Internal Medicine Department Hospital General de MéxicoDr.Eduardo LiceagaMexico City 06720Mexico Fundación Mexicana para la Salud A.C Mexico City 06720Mexico

AIM:To evaluate the impact of metadoxine(MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis(AH).METHODS:This study was an open-label clinical trial,performed at the"Hospital General de México,Dr.Eduardo Liceaga".We randomized 135 patients who met the criteria for severe AH into the following groups:35 patients received prednisone(PDN)40 mg/d,35patients received PDN+MTD 500 mg three times daily,33 patients received pentoxifylline(PTX)400 mg three times daily,and 32 patients received PTX+MTD 500 mg three times daily.The duration of the treatment for all of the groups was 30 d.RESULTS:In the groups treated with the MTD,thesurvival rate was higher at 3 mo(PTX+MTD 59.4%vs PTX 33.3%,P=0.04;PDN+MTD 68.6%vs PDN20%,P=0.0001)and at 6 mo(PTX+MTD 50%vs PTX18.2%,P=0.01;PDN+MTD 48.6%vs PDN 20%,P=0.003)than in the groups not treated with MTD.A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo.The patients receiving MTD maintained greater abstinence than those who did not receive it(74.5%vs 59.4%,P=0.02).CONCLUSION:MTD improves the 3-and 6-mo survival rates in patients with severe AH.Alcohol abstinence is a key factor for survival in these patients.The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.

关键词： Alcoholic hepatitis Metadoxine Survival Alcohol abstinence

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Colonic　Dialysis　Therapy　of　Chinese　Herbal　Medicine　in　abstinence　of　Heroin　Addicts-Report　of　75　Cases

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Chinese Journal of Integrative Medicine 1997年第2期3卷 113-113页

作者：沙丽君张志祥程琳霞

Ｃｏｌｏｎｉｃ　Ｄｉａｌｙｓｉｓ　Ｔｈｅｒａｐｙ　ｏｆ　Ｃｈｉｎｅｓｅ　Ｈｅｒｂａｌ　Ｍｅｄｉｃｉｎｅ　ｉｎ　Ａｂｓｔｉｎｅｎｃｅ　ｏｆ　Ｈｅｒｏｉｎ　Ａｄｄｉｃｔｓ－Ｒｅｐｏｒｔ　ｏｆ　７５　ＣａｓｅｓＳＨＡＬｉ－... 详细信息

Ｃｏｌｏｎｉｃ　Ｄｉａｌｙｓｉｓ　Ｔｈｅｒａｐｙ　ｏｆ　Ｃｈｉｎｅｓｅ　Ｈｅｒｂａｌ　Ｍｅｄｉｃｉｎｅ　ｉｎ　Ａｂｓｔｉｎｅｎｃｅ　ｏｆ　Ｈｅｒｏｉｎ　Ａｄｄｉｃｔｓ－Ｒｅｐｏｒｔ　ｏｆ　７５　ＣａｓｅｓＳＨＡＬｉ－ｊｕｎ；ＺＨＡＮＧＺｈｉ－ｘｉａｎ...

关键词： Chinese Therapy Dialysis Herbal Medicine Addicts-Report abstinence

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Liver transplantation in acute alcoholic hepatitis:Current status and future development

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World Journal of Hepatology 2011年第8期3卷 215-218页

作者： Ashwani K Singal Andrea Duchini Division of Gastroenterology and Hepatology Mayo ClinicRochesterMN 55905-0001United States

Acute alcoholic hepatitis (AH) is a distinct clinical entity amongst patients with chronic alcohol abuse.Patients with severe AH are at risk of dying in about 20%-25% cases despite specific treatment with corticosteroids and/or pentoxifylline.Clearly,a need for an additional more effective treatment option is unmet currently.Liver transplantation (LT),a definitive treatment option for alcoholic cirrhosis requires 6 mo abstinence.However,this rule cannot be applied to patients with AH as these patients are actively drinking prior to their presentation.Shortage of donors,ethical issues,and fear of recidivism after transplantation with less than 6 mo pretransplant abstinence are some of the reasons behind this rule of 6 mo of abstinence and hesitancy of transplanting patients with AH.These issues are debated at length in this manuscript.Further,retrospective studies have shown that patients undergoing transplantation for alcoholic cirrhosis and having histological changes of AH have been shown to fare as well when compared to patients without these histological changes.Recently,French workers have reported a case matched prospective study showing encouraging data on the usefulness of LT for patients who are non-responders to cortico-steroid and/or pentoxifylline therapy.Future studies are needed to identify patients with severe AH who are going to benefit most with LT.In the light of emerging data on the efficacy of LT in improving survival of patients with severe acute AH who do not respond to corticosteroids,the time is ripe to re-evaluate our policy of LT in patients with AH.

关键词： Alcoholic hepatitis Liver transplantation Recidivism Alcohol abstinence

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General aspects of the treatment of alcoholic hepatitis

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World Journal of Hepatology 2011年第5期3卷 126-130页

作者： Michael J Babineaux Bhupinderjit S Anand Department of Internal Medicine University of Texas Medical BranchGalvestonTX 77555United States Department of Gastroenterology and He-patology Michael Debakey VA Medical CenterBaylor College of MedicineHoustonTX 77555United States

General measures for treating patients with alcoholic hepatitis(AH) are similar irrespective of the disease severity.Alcohol abstinence is the cornerstone of treatment and can be achieved with appropriate social support,Alcoholics Anonymous and sometimes pharmacological therapy.Alcohol withdrawal should be anticipated and treatment initiated to prevent this complication.Treatment for complications of cirrhosis should be as for any other patient with cirrhosis.AH patients are particularly prone to infections and malnutrition.These should be identified and treated appropriately using broad spectrum antibiotics and nutritional support respectively.

关键词： Alcoholic hepatitis Alcohol abstinence Alcohol withdrawal Nutritional support Complications of cirrhosis Malnutrition Treatment

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