关于大鼠肺和肝脏胞浆乙醇脱氢酶活性的比较研究

已知肝脏是乙醇氧化代谢的主要器官,肝脏乙醇脱氢酶(ADH)又是参与乙醇氧化的最主要的酶。某些研究表明,肺脏胞浆ADH也参与乙醇的氧化代谢。为了进一步了解肺脏ADH在乙醇代谢中的作用,本文对大鼠肺和肝脏ADH活性进行了比较研究。实验采用差速离心及Sephadex G-50层析柱等方法,分别制备肝和肺细胞浆,同时分别测定了肝脏和肺脏的胞浆ADH活性、ADH动力学常数等,并观察了pH对肝、肺ADH活性的影响。结果表明,在pH为中性的缓冲体系中,肺脏ADH活性比在pH为9或10的碱性缓冲体系中低得多。肝脏ADH活性尽管亦受pH影响,     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

乙醇脱氢酶和乙醛脱氢酶基因多态性及饮酒与胃癌的关系

个体酒精代谢的差异是由于乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素P4502E1等的基因多态性所致,被摄取至肝脏的乙醇大部分被肝细胞液中的ADH催化脱氧而牛成乙醛,ALDH的主要作用是将有毒的乙醛氧化为无毒的乙酸,后者进入三羧酸循环后,最终代谢成为二氧化碳和水而排出体外,其中约有90%在肝脏中完成[1].     

Alcohol drinking, mean corpuscular volume of erythrocytes, and alcohol metabolic genotypes in drunk drivers

Regular and irregular abuse of alcohol are global health priorities associated with diseases at multiple sites, including cancer. Mechanisms of diseases induced by alcohol are closely related to its metabolism. Among conventional markers of alcohol abuse, the mean corpuscular volume (MCV) of erythrocytes is prognostic of alcohol-related cancer and its predictivity increases when combined with functional polymorphisms of alcohol dehydrogenase (ADH1B [rs1229984] and ADH1C [rs698]) and the mitochondrial aldehyde dehydrogenase (ALDH2 [rs671]). Whether these genetic variants can influence abuse in alcohol drinking and MCV has never been examined in drunk-driving traffic offenders. We examined 149 drunk drivers, diagnosed as alcohol abusers according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition Text Revision (DSM-IV-TR) and enrolled in a probation program, and 257 social drinkers (controls), all Caucasian males. Alcohol intake was assessed according to self-reported drink-units/d and MCV unadjusted and adjusted for age, smoking, and body mass index. Multivariable models were used to compute MCV adjusted means. Genotype analyses were performed by PCR on DNA from blood. The adjusted MCV mean was higher in drunk-driving abusers than in controls (92 vs. 91 fL; P < .0001) and increased with the number of drink-units/d in both abusers and controls (P-trend = .0316 and .0089) already at intermediate quantities (0-1 vs. 2-4 drink-units/d: P = .054 and .024). Carriers of the common ADH1B*1/*1 (rs1229984) genotype were more likely to be drunk-driving abusers (P = .008), reported higher drink-units/d (P = .0126), and had larger MCV (P = .035). The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with MCV. ADH1B*1/*1 polymorphism is significantly associated with being a drunk-driving abuser, higher alcohol drinking, and MCV enlargement. This suggests that drunk drivers with augmented MCV modulated by the alcohol metabolic ADH1B*1/*1 genotype may be at higher risk of driving incapability and of alcohol-related cancer.     

Phenotype prediction of deleterious nonsynonymous single nucleotide polymorphisms in human alcohol metabolism-related genes: a bioinformatics study

Nonsynonymous single nucleotide polymorphisms (nsSNPs) are thought as potential disease modifiers because they alter the encoded amino acid sequence and are likely to affect the function of the proteins accounting for susceptibility to disease. Distinguishing the functionally significant nsSNPs from tolerant nsSNPs is helpful to characterize the genetic basis of human diseases and assess individual susceptibility to diseases. Many nsSNPs have been found in alcohol metabolism-related genes but there is poor knowledge on the relationship between the genotype and phenotype of nsSNPs in these genes. In this study, we have identified a total of 203 nsSNPs in 29 human alcohol metabolism-related genes from the National Center for Biotechnology Information (NCBI) dbSNP and SWISS-Prot databases. Using the PolyPhen and SIFT algorithms, 43% of nsSNPs in alcohol metabolism-related genes were predicted to have functional impacts on protein function with a significant concordance of the prediction results between the two algorithms. The prediction accuracy is about 77-81% of all the nsSNPs based on the results of in vivo and in vitro studies. These amino acid substitutions are supposed to be the pathogenetic basis for the alteration of metabolism enzyme activity and the association with disease susceptivity. The phenotype of nsSNPs predicted as deleterious needs to be clarified in further studies and the prediction of nsSNPs in human alcohol metabolism-related genes would be useful hints for further genotype-phenotype studies on the individual difference in susceptivity to alcohol-related diseases.     

Alcohol questionnaires and HDL: Screening scores as scaled markers of alcohol consumption

Improving the quality of alcohol-related care requires practical approaches to assessing alcohol consumption to guide management and monitor outcomes. Given the increasing use of alcohol screening questionnaires to identify alcohol misuse it would be ideal if scores on screening questionnaires were also indicators of average alcohol consumption. However, the questionnaires were not designed for this purpose and include dimensions of drinking that may not reflect average consumption (e.g. heavy episodic drinking, alcohol-related problems). In a general population sample, scores on the AUDIT-C screen correlated with reports of alcohol consumption in detailed interviews, but the relationship is unknown for clinical populations and other questionnaires. Serum high-density lipoprotein cholesterol (HDL) is a biomarker routinely obtained in clinical care and is known to rise with average alcohol consumption. This cross-sectional study of 11,175 male U.S. Veterans Affairs patients enrolled in a primary care study used HDL as an objective biomarker to evaluate whether average alcohol consumption increased as scores increased on 3 brief alcohol screens – the AUDIT-C, AUDIT Question #3 (a single-item screen), and the CAGE questionnaire. Mean HDL progressively increased as screening scores increased for the AUDIT-C and AUDIT Question #3: about 12 mg/dL from the lowest to the highest scores. The association was much weaker for the CAGE questionnaire. Results were minimally affected by adjustment for covariates (e.g. age, race, medical comorbidity, smoking, medication count, and depression) but the association was modified (p = 0.008) and mildly attenuated by adherent use of lipid-lowering medications. This study using HDL as a biomarker of average alcohol consumption adds to evidence that some alcohol screening scores may also serve as scaled markers of average alcohol consumption.     

Legal interventions to reduce alcohol-related cancers

Research and public policy literature on alcohol-related harm predominantly focuses on the impact of alcohol policies over the short term. However, evidence on the effect of interventions on long-term, alcohol-related chronic disease, including cancers, is growing. The experience from tobacco control supports the use of interventions that increase the price of a commodity and restrict its availability in order to reduce consumption and realize long-term health gains. Meanwhile, the negative involvement of the alcohol industry in alcohol policy development is hampering efforts to intervene early and potentially save many lives. As the burden of alcohol-related cancers becomes more apparent, effective alcohol policies should be introduced sooner rather than later. This paper looks at some of the key legal interventions to reduce alcohol consumption, the potential for these interventions to reduce the risk of alcohol-related cancers, and some of the barriers to implementing these interventions. Examples of law reform efforts in Australia, New Zealand and the UK are given, as well as a short discussion of global alcohol policy initiatives.     

Nutritional profiles of chronic alcoholics.

An epidemiological study of 58 variables from 300 chronic alcoholic and normal subjects was carried out in the Cardiology, Gastroenterology, Neurology, Psychiatry and Alcohology Departments in order to research, within this chronic alcoholic population, a correlation between diet, alcohol intake, tobacco use and the various alcohol-related diseases. A standardized questionnaire (previously tested) was used to relate dietary intakes (proteins, fats, carbohydrates, water and energy) to drinking and smoking habits. Discriminant analyses were used as appropriate. The alcoholic population is made up of subjects with strong oral-intake behaviour and can be classified in relation to their alcohol-related diseases. The alcoholics with cardiovascular and digestive diseases have the two (1st and 2nd) richest diets, respectively, consisting mainly of saturated fats and animal proteins, together with the lowest daily alcohol intake, the highest recorded total quantities of alcohol intake and the longest period of alcohol abuse before alcohol-related disease diagnosis. The 4th and 5th places can be reserved for the alcoholics with neurological and psychiatric diseases with opposite eating and drinking behaviours, i.e. with the poorest diet (less in terms of proteins and fats, although more than the normal population), the highest daily alcohol intake, the lowest quantities of total alcohol intake and the shortest time of alcohol abuse before disease diagnosis. The alcoholic population with subjects free of alcohol-related disease including mixed subjects, who either had not yet started or will never present any alcohol-related disease, occupy the intermediate place (3rd) in this classification.     

汉族健康人201名的酒精代谢相关酶基因多态型分布

目的 了解乙醇脱氢酶2(ADH2)基因型和乙醛脱氢酶2(ALDH2)基因型的分布情况,为筛选高危敏感个体和采取预防措施以减少酒精相关性疾病的发生提供理论基础。方法 问卷调查筛选出居住在四川省的无直接血缘关系的汉族健康个体201人(男104人,女97人)、采集血样并搜集饮酒行为资料;聚合酶链式反应．限制性片段长度多态性方法测定ADH2、ALDH2基因型。结果 杂合型ADH2与纯合型ALDH2在中国汉族正常人口中占优势(分别为53．23％,68．16％);9种ADH2、ALDH2基因型组合的分布间差异无统计学意义;纯合型ALDH2在具高、中饮酒频率男性中的分布间差异有统计学意义。结论 汉族正常人口中携带酒精相关性疾病易感基因型个体占多数(68．16％),应加强监测与预防酒精相关性疾病的工作。     

A pilot study investigating of the nature of point-of-sale alcohol promotions in bottle shops in a large Australian regional city

OBJECTIVE: The promotion of alcohol by retailers and media can contribute to a culture of excessive alcohol consumption, but the effect of non-advertising alcohol promotions has largely been neglected. This study sought to gather initial data on this important area. METHOD: An observational study of alcohol point-of-sale promotions in the Wollongong CBD area, conducted in July-August 2005. RESULTS: We identified 17 different promotions in three categories: gift with purchase; competitions; and buy some, get some free. CONCLUSION: Given previous research demonstrating the relationship between increased alcohol consumption and both ownership of alcohol-related merchandise and reduced per unit price, it appears that point-of-sale promotions may have the potential to further increase alcohol consumption among young people. IMPLICATIONS: Only when the extent and impact of such promotions is demonstrated will we be in a position to effectively advocate for appropriate regulations to ensure young people are not exposed to marketing strategies that further increase their exposure to alcohol-related harms.     

Opportunities for prevention of alcohol-related death in primary care: Results from a population-based cross-sectional study

The mortality rate from alcohol-related conditions has risen sharply in the United Kingdom and it is not known whether opportunities for preventive interventions could be improved. The purpose of our study was to identify opportunities to detect, assess, and manage alcohol problems in primary care according to evidence-based guidelines. We carried out a cross-sectional study on patients who died from alcohol-related conditions in the calendar year 2003 within National Health Service Greater Glasgow Health Board area, Scotland (population 920,000). We described patient characteristics and care recorded in health service records, comparing it with best evidence-based practice in Scottish Intercollegiate Guidelines Network and Health Technology Board for Scotland recommendations on the management of harmful drinking and alcohol dependence. 501 deaths occurred from an alcohol-related cause. The mean age at death was 57.5 years and 72% were male. The most common causes of death, recorded by the International Classification of Diseases, revision 10, excluding accidents, were alcoholic liver disease (290, 57.9%) and mental and behavioural disorders due to alcohol (70, 14.0%). Lifetime mean consultations at primary care general practitioner and hospital outpatient departments were 24 in males and 5 in females. All individuals who died from an alcohol-related cause had at least one biochemical or physical indicator suggestive of alcohol misuse. 21% (95% CI 13–33%) had no record of having been advised to abstain from alcohol and 23% (95% CI 15–35%) had received brief interventions. 58% (95% CI 46–70%) had been referred to specialist alcohol services but a third of them did not attend. The majority of patients (83%, 95% CI 72–90%) had no evidence of shared health service and social work care. We concluded that individuals who died from alcohol-related conditions were usually in contact with statutory and voluntary services but further efforts were required to use these opportunities to detect, assess, and manage serious alcohol problems according to evidence-based guidelines.     

Alcohol licensing data: Why is it an underused resource in public health?

Alcohol-related harm is related to alcohol availability. Due to complex regulatory and environmental factors, alcohol availability varies spatially. However, the extent of this variation is largely unknown in the UK, despite its potential influence on patterns of alcohol-related harm. We investigate why administrative data is underused in the study of alcohol-related harm in the UK. We found that local authorities routinely collect a rich supply of licensing data. However, this information is stored in databases that are sometimes difficult to access. With greater coordination between researchers and practitioners, this data can be used to fulfil its primary administrative purpose and also contribute to understanding and prevention of alcohol-related health and social problems.