Separately, chronic alcohol ingestion and HIV-1 infection are associated with severe skeletal muscle derangements, including atrophy and wasting, weakness, and fatigue. One prospective cohort study reported that 41% of HIV-infected patients met the criteria for alcoholism, however; few reports exist on the co-morbid effects of these two disease processes on skeletal muscle homeostasis.
Thus, we analyzed the atrophic effects of chronic alcohol ingestion in HIV-1 transgenic rats and identified alterations to several catabolic and anabolic factors.
Relative plantaris mass, total protein content, and fiber cross-sectional area were reduced in each experimental group compared to healthy, control-fed rats. Alcohol abuse further reduced plantaris fiber area in HIV-1 transgenic rats. Consistent with previous reports, gene levels of myostatin and its receptor activin IIB were not increased in HIV-1 transgenic rat muscle.
However, myostatin and activin IIB were induced in healthy and HIV-1 transgenic rats fed alcohol for 12 weeks. Catabolic signaling factors such as TGFbeta1, TNFalpha, and phospho-p38/total-p38 were increased in all groups compared to controls. There was no effect on IL-6, leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), or ciliary neurotrophic factor (CNTF) in control-fed, transgenic rats.
However, the co-morbidity of chronic alcohol abuse and HIV-1-related protein expression decreased expression of the two anabolic factors, CT-1 and CNTF.
Consistent with previous reports, alcohol abuse accentuated skeletal muscle atrophy in an animal model of HIV/AIDS. While some catabolic pathways known to drive alcoholic or HIV-1-associated myopathies were also elevated in this co-morbid model (e.g., TGFbeta1), consistent expression patterns were not apparent.
Thus, specific alterations to signaling mechanisms such as the induction of the myostatin/activin IIB system or reductions in growth factor signaling via CT-1- and CNTF-dependent mechanisms may play larger roles in the regulation of muscle mass in alcoholic, HIV-1 models.
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MoDOT is launching a new smartphone application to help people make smart choices about designating a sober driver.
The "Show Me My Buzz" free smartphone app, available soon in the Apple App Store and the Google Market, allows users to calculate their estimated blood-alcohol concentration (BAC) based on how many drinks they have consumed, how long they have been drinking and their gender.
"Drinking and driving is always a bad decision because even a small amount of alcohol affects your reflexes," said Don Hillis, MoDOT's assistant chief engineer. "This new app is a creative way to get people talking about the subject and then finding a sober driver."
The app indicates designating a driver who has not been drinking is the only safe option, and it will even provide the phone number of a local cab company with just a tap of the screen.
"The added feature of finding a phone number for a taxi in more urban locations, takes away one more excuse for a person who has been drinking," said Hillis. "It is easy to just touch the button to call a cab." > > > > Read More
Alcoholism is associated with alterations of the hypothalamus–pituitary–gonadal hormone axis. We recently reported a leptin-mediated relation between the CAGn polymorphism of the androgen receptor and craving during alcohol withdrawal. This study investigated whether the TTTAn polymorphism of the aromatase (CYP19A1) is equally linked to craving.
An association between TTTAn and compulsive craving (p
=0.029) was revealed in our sample of 118 male alcohol addicts at day of hospital admission. Genotype-dependent subgroups showed differences in that the patients with short alleles suffered from lower compulsive craving during withdrawal than those with the longer alleles (p=0.027). The additional inclusion of leptin revealed no further significant association in the present study.
Our finding is a further step on the way to elucidate the genesis of craving for alcohol with its extensive underlying interactions of different genetic and non-genetic factors. Future investigations should enrol women and consider sex hormone levels for further clarification of the observed TTTAn-craving relationship.
Request Reprint E-Mail: bernd.lenz@uk-erlangen.de
We investigated tobacco companies’ knowledge about concurrent use of tobacco and alcohol, their marketing strategies linking cigarettes with alcohol, and the benefits tobacco companies sought from these marketing activities.
We performed systematic searches on previously secret tobacco industry documents, and we summarized the themes and contexts of relevant search results.
Tobacco company research confirmed the association between tobacco use and alcohol use. Tobacco companies explored promotional strategies linking cigarettes and alcohol, such as jointly sponsoring special events with alcohol companies to lower the cost of sponsorships, increase consumer appeal, reinforce brand identity, and generate increased cigarette sales. They also pursued promotions that tied cigarette sales to alcohol purchases, and cigarette promotional events frequently featured alcohol discounts or encouraged alcohol use.
Tobacco companies’ numerous marketing strategies linking cigarettes with alcohol may have reinforced the use of both substances. Because using tobacco and alcohol together makes it harder to quit smoking, policies prohibiting tobacco sales and promotion in establishments where alcohol is served and sold might mitigate this effect. Smoking cessation programs should address the effect that alcohol consumption has on tobacco use.
Request Reprint E-Mail: pling@medicine.ucsf.edu
Based on the fact that energy content in 1 gram of alcohol is 29 kJ or 7.1 kcal, alcohol consumption can lead to weight gain. The present review was conducted to analyze the effects of alcohol consumption on body weight.
A search of the Medline database for the period 1984 to March 2010 was conducted to identify cross-sectional, prospective cohort studies and intervention trials investigating the relationship between alcohol consumption and the risk of weight gain. Thirty-one publications were selected on the basis of relevance and quality of design and methods.
The findings from large cross-sectional studies as well as from well-powered, prospective, cohort studies with long periods of follow-up were contradictory. Findings from short-term experimental trials also did not show a clear trend.
The overall results do not conclusively confirm a positive association between alcohol consumption and weight gain; however, positive findings between alcohol intake and weight gain have been reported, mainly from studies with data on higher levels of drinking. It is, therefore, possible that heavy drinkers may experience such an effect more commonly than light drinkers. Moreover, light-to-moderate alcohol intake, especially wine intake, may be more likely to protect against weight gain, whereas consumption of spirits has been positively associated with weight gain.
Further research should be directed towards assessing the specific roles of different types of alcoholic beverages. Studies should also take the effect of consumption patterns into account. In addition, a potential effect modifier that has not been evaluated before but might be important to consider is the subjects' previous tendency to gain weight.
Request Reprint E-Mail: mbes@unav.es,
Examine the reciprocal effects between the onset and course of alcohol use disorder (AUD) and normative changes in personality traits of behavioral disinhibition and negative emotionality during the transition between adolescence and young adulthood.
Longitudinal-epidemiological study assessing AUD and personality at age 17 and 24.
Participants were recruited from the community and took part in a day-long, in-person assessment.
Male (n = 1161) and female (n = 1022) twins participating in the Minnesota Twin Family Study.
The effects of onset (adolescent versus young adult) and course (persistent versus desistent) of AUD on change in personality traits of behavioral disinhibition and negative emotionality from age 17 to 24.
Onset and course of AUD moderated personality change from age 17 to 24. Adolescent onset AUD was associated with greater decreases in behavioral disinhibition. Those with an adolescent onset and persistent course failed to exhibit normative declines in negative emotionality. Desistence was associated with a “recovery” toward psychological maturity in young adulthood, while persistence was associated with continued personality dysfunction. Personality traits at age 11 predicted onset and course of AUD, indicating personality differences were not due to active substance abuse.
Personality differences present prior to initiation of alcohol use increase risk for alcohol use disorder, but the course of alcohol use disorder affects the rate of personality change during emerging adulthood. Examining the reciprocal effects of personality and alcohol use disorder within a developmental context is necessary to improve understanding of theory and intervention.
To assess the short-term temporal relationship between emergency department (ED) attendances for acute alcohol problems and assaults reported to police.
Cross-sectional time series analysis.
Population of New South Wales (NSW), Australia between 2003 and 2008.
All patients who attended any of 56 large NSW public hospital EDs and had a recorded diagnosis of acute alcohol problems, and all persons involved in assault incidents reported to the NSW Police Force.
Weekly count time series were formed for ED attendances, assault incidents and persons of interest in assault incidents. Cross correlation analysis was used to determine any time lag in the relationship between the alcohol and the assault series. Poisson regression was used to assess the magnitude of the relationship. Splines of week controlled for seasonality.
There was no time lag found between the ED and police series. A weekly increase of 100 attendances in persons 15 years and above to EDs for alcohol problems was associated with an 11% (95% confidence interval (CI) 7%-15%) increase in the number of incident assaults attended by police. The relationship was similar and statistically significant for domestic and non-domestic assaults and urban areas. The association was stronger between ED attendances and persons of interest aged 15-24 year-olds (23%, 95% CI 17%-29%), 15-24 year-old males (39%, 95% CI: 16%-66%) and 15-24 year-old females (66%, 95% CI: 20%-129%).
There is a clear, short-term temporal association between independent population level markers of excessive alcohol use and violence.
In April 2011 the funding for drug treatment in prisons passed from the MOJ to the DOH and with it the responsibility to commission these services passed to local partnerships. Many of those with the commissioning responsibility are new to the prison setting and are stepping into unfamiliar territory. There are questions like:
Despite the importance of heavy drinking and alcohol dependence among patients with opiate and cocaine dependence, few studies have evaluated specific interventions within this group. The aim of the present study was to evaluate the impact of screening with the Alcohol Use Disorders Identification Test (AUDIT) and of brief intervention (BI) on alcohol use in a sample of patients treated for opioid or cocaine dependence in a specialized outpatient clinic.
Adult outpatients treated for opioid or cocaine dependence in Switzerland were screened for excessive alcohol drinking and dependence with the AUDIT. Patients with AUDIT scores that indicated excessive drinking or dependence were randomized into two groups--treatment as usual or treatment as usual together with BI--and assessed at 3 months and 9 months.
Findings revealed a high rate (44%) of problematic alcohol use (excessive drinking and dependence) among patients with opiate and cocaine dependence. The number of drinks per week decreased significantly between T0 (inclusion) and T3 (month 3). A decrease in average AUDIT scores was observed between T0 and T3 and between T0 and T9 (month 9). No statistically significant difference between treatment groups was observed.
In a substance abuse specialized setting, screening for alcohol use with the AUDIT, followed by feedback on the score, and use of alcohol BI are both possibly useful strategies to induce changes in problematic alcohol use. Definitive conclusions cannot, however, be drawn from the study because of limitations such as lack of a naturalistic group. An important result of the study is the excellent internal consistency of AUDIT in a population treated for opiate or cocaine dependence.
The Task Force on Community Preventive Services recommends the use of dram shop liability laws, on the basis of strong evidence of effectiveness in preventing and reducing alcohol-related harms. The Task Force found insufficient evidence to determine the effectiveness of overservice law enforcement initiatives as a means to reduce excessive alcohol consumption and related harms, because too few studies were identified and findings were inconsistent.
Request Reprint E-Mail: rhahn@cdc.gov
Dram shop liability holds the owner or server(s) at a bar, restaurant, or other location where a patron, adult or underage, consumed his or her last alcoholic beverage responsible for harms subsequently inflicted by the patron on others. Liability in a state can be established by case law or statute. Overservice laws prohibit the sale of alcoholic beverages to intoxicated patrons drinking in on-premises retail alcohol outlets (i.e., premises where the alcohol is consumed where purchased); enhanced enforcement of these laws is intended to ensure compliance by premises personnel. Both of these interventions are ultimately designed to promote responsible beverage service by reducing sales to intoxicated patrons, underage youth, or both. This review assesses the effectiveness of dram shop liability and the enhanced enforcement of overservice laws for preventing excessive alcohol consumption and related harms.
Studies assessing alcohol-related harms in states adopting dram shop laws were evaluated, as were studies assessing alcohol-related harms in regions with enhanced overservice enforcement. Methods previously developed for systematic reviews for the Guide to Community Preventive Services were used.
Eleven studies assessed the association of state dram shop liability with various outcomes, including all-cause motor vehicle crash deaths, alcohol-related motor vehicle crash deaths (the most common outcome assessed in the studies reviewed), alcohol consumption, and other alcohol-related harms. There was a median reduction of 6.4% (range of values 3.7% to 11.3% reduction) in alcohol-related motor vehicle fatalities associated with the presence of dram shop liability in jurisdictions where premises are licensed. Other alcohol-related outcomes also showed a reduction. Only two studies assessed the effects of enhanced enforcement initiatives on alcohol-related outcomes; findings were inconsistent, some indicating benefit and others none.
According to Community Guide rules of evidence, the number and consistency of findings indicate strong evidence of the effectiveness of dram shop laws in reducing alcohol-related harms. It will be important to assess the possible effects of legal modifications to dram shop proceedings, such as the imposition of statutes of limitation, increased evidentiary requirements, and caps on recoverable amounts. According to Community Guide rules of evidence, evidence is insufficient to determine the effectiveness of enhanced enforcement of overservice laws for preventing excessive alcohol consumption and related harms.
Internet-based alcohol misuse prevention programs are now used by many universities. One popular 2- to 3-hour online course known as AlcoholEdu for College is typically required for all incoming freshmen and thus constitutes a campus-level strategy to reduce student alcohol misuse.
Multi-campus study to evaluate the effectiveness of an Internet-based alcohol misuse prevention course.
RCT with 30 universities: 21 entered the study in Fall 2007, nine in Fall 2008. Fifteen were randomly assigned to receive the online course and the other 15 were assigned to the control condition. The course was implemented by intervention schools during the late summer and/or fall semester. Cross-sectional surveys of freshmen were conducted at each university, beginning prior to the intervention in Spring 2008–2009; post-intervention surveys were administered in Fall 2008–2009 and Spring 2009–2010.
Public and private universities of varying sizes across the U.S. Random samples of 200 freshmen per campus were invited to participate in online surveys for the evaluation. Overall survey response rates ranged from 44% to 48% (M ≈ 90 participants per campus).
The online course includes five modules; the first four (Part I) are typically offered in the late summer before matriculation, and the fifth (Part II) in early fall. Course content includes defining a standard drink, physiologic effects of alcohol, the need to monitor blood alcohol level, social influences on alcohol use, alcohol laws, personalized normative feedback, and alcohol harm-reduction strategies. Students must pass an exam after Part I to advance to Part II.
Past-30-day alcohol use, average number of drinks per occasion, and binge drinking.
Multilevel intent-to-treat analyses indicated significant reductions in the frequency of past-30-day alcohol use (beta = –0.64, p<0.05) and binge drinking (beta = –0.26, p<0.05) during the fall semester immediately after completion of the course. However, these effects did not persist when assessed in the spring semester. Post hoc comparisons suggested stronger course effects on these outcomes at colleges with higher rates of student course completion. No course effects were observed for average number of drinks per occasion or prevalence of binge drinking, regardless of the campus course completion rate.
This study provides initial evidence that the Internet-based alcohol misuse prevention course has beneficial short-term effects on hazardous drinking behavior among first-year college students, which should be reinforced through effective environmental prevention strategies.
HEALTH warnings linking alcohol with dire outcomes such as brain damage and cancer have been backed by health groups but described as potentially ''alarming'' by an industry-backed group.
The fight over safety labels between the health sector and the multibillion-dollar liquor industry is warming up just as the federal government finally begins formal consultations today on long-awaited warnings, introduced in the United States 22 years ago.
The federally-funded Alcohol Education and Rehabilitation Foundation yesterday released its favoured warnings, including: ''Drinking alcohol increases your risk of developing cancers'' and ''drinking alcohol damages the young developing brain''.
The foundation has dismissed as ''weak'' the voluntary warnings being introduced by most beer, wine and spirit companies.
The foundation's warnings have been developed on advice from health promotion experts and were backed by the Australian Medical Association, which has urged the government to introduce tough mandatory warnings. > > > > Read More
+ Author Affiliations
Chronic and intermittent alcohol consumption leads to cognitive impairment in the brain due to the ethanol's action on specific neurotransmitter systems and intricate signalling pathways. Glial cells actively participate in brain function by nurturing neurons and facilitating neuronal activity as well having an immunological role to protect brain cells from invading pathogens. Dysregulation of this immune function induced by intermittent alcohol abuse may shift the homeostatic balance of inflammatory mediators to a proinflammatory state, activating microglia and inducing neuronal loss thereby inducing behavioural and cognitive impairments. Molecules, which could prevent the microglial activation and cytokine production would downregulate the pro-inflammatory state and help to prevent the decline of cognitive impairment. Studies of a ‘binge drinking’ adolescent female rats identified increased levels of glutamate in the dentate gyrus region of the hippocampus, which were associated with activated microglia. Such microglia will release glutamate when activated as well as a plethora of pro-inflammatory cytokines, e.g. IL-6 and TNFα. Oral administration of a taurine analogue, ethane-β-sultam to such ‘binge drinking’ rats for a 3-week period stabilized IKBα within the microglial cell, thereby preventing NFkappaB translocation to the nucleus and cytokine production. Activated microglia were no longer visible after immunohistochemical staining of the dentate gyrus brain region. The innate immune system, which is activated by intermittent alcohol use, can be suppressed by the use of molecules which target specific activators of this system, i.e. NFkappaB.
ERAB funding is gratefully acknowledged.
+ Author Affiliations
Alcohol dependence and associated cognitive impairment appear to result from maladaptive neuroplasticity in response to chronic alcohol consumption, neuroinflammation and neurodegeneration. The inherent stability of behavioral alterations associated with the addicted state suggests that transcriptional and epigenetic mechanisms are operative. NF-kappaB transcription factors are regulators of synaptic plasticity and inflammation, and responsive to a variety of stimuli including alcohol. These factors are abundant in the brain where they have diverse functions that depend on the composition of the NF-kappaB complex and cellular context. In neuron cell bodies, NF-kappaB is constitutively active, and involved in neuronal injury and neuroprotection. However, at the synapse, NF-kappaB is present in a latent form and upon activation is transported to the cell nucleus. In glia, NF-kappaB is inducible and regulates inflammatory processes that exacerbate alcohol-induced neurodegeneration. Animal studies demonstrate that acute alcohol exposure transiently activates NF-kappaB, which induces neuroinflammatory responses and neurodegeneration. Our postmortem studies of brains of human alcoholics suggest that cycles of alcohol consumption/withdrawal cause adaptive changes in the NF-kappaB system that permit the system to better tolerate excessive stimulation. This tolerance, ensuring a low degree of responsiveness to applied stimuli, may represent a compensatory response that protects brain cells against alcohol neurotoxicity. This is supported by findings showing preferential downregulation of pro-apoptotic gene expression in the affected brain areas in human alcoholics. Although further verification is needed, we speculate that NF-kappaB-driven neuroinflammation and disruption to neuroplasticity play a significant role in regulating alcohol dependence and cognitive impairment.
+ Author Affiliations
Toll-like receptors (TLRs) play an important role in the innate immune response, and emerging evidence indicates their role in brain injury and neurodegeneration. Our recent results have demonstrated that ethanol is capable of activating glial TLR4 receptors and that the elimination of these receptors in mice protects against ethanol-induced glial activation, induction of inflammatory mediators and apoptosis. However, whether ethanol-induced inflammatory damage causes behavioural and cognitive consequences, and if behavioural alterations are dependent of TLR4 functions are presently unknown. Here we show in mice drinking alcohol for 5 months, followed by a 15-day withdrawal period, that activation of the astroglial and microglial cells in frontal cortex and striatum is maintained and that these events are associated with cognitive and anxiety-related behavioural impairments in wild-type (WT) mice, as demonstrated by testing the animals with object memory recognition, conditioned taste aversion and dark and light box anxiety tasks. Mice lacking TLR4 receptors (TLR4−/−) are protected against ethanol-induced inflammatory damage, and behavioural associated effects. We further assess the possibility of the epigenetic modifications participating in short- or long-term behavioural effects associated with neuroinflammatory damage. We show that chronic alcohol treatment decreases H4 histone acetylation and histone acetyltransferases activity in frontal cortex, striatum and hippocampus of WT mice. Alterations in chromatin structure were not observed in TLR4−/− mice. These results provide the first evidence of the role that TLR4 functions play in the behavioural consequences of alcohol-induced inflammatory damage and suggest that the epigenetic modifications mediated by TLR4 could contribute to short- or long-term alcohol-induced behavioural or cognitive dysfunctions.
This study was supported by SAF-2009-07503, Institute of Heath, Carlos III (RTA-Network).
+ Author Affiliations
Addiction evolves through progressively reduced behavioral control and cognitive flexibility with increasing negative emotion and craving. Recent discoveries indicating neuroimmune signaling contribute to addiction and co-morbid depression. Low threshold microglia undergoes progressive stages of innate immune activation involving astrocytes and neurons with repeated drug abuse, stress and immune signals. Increased brain NF-κB transcription of proinflammatory chemokines, cytokines, oxidases, proteases, TLR and other genes create loops amplifying NF-κB transcription and neuroimmune gene expression. Human post-mortem alcoholic brain has increased microglial markers, chemokine-MCP1, TLR receptors and endogenous TLR agonists. Ethanol activates persistent neuroimmune signaling through the formation of loops of NF-κB transcription in glia contributing to a hyperglutamate state. Chronic ethanol treatment induces reversal learning deficits coincident with frontal cortical damage mimicking human drug addict deficits in behavioral flexibility. Increasing limbic negative emotion and depression-like behavior are reflected in hippocampal neurogenesis. Chronic ethanol inhibits neurogenesis coincident with depression-like behavior with both reversed by antidepressants. Antidepressants, naltrexone and anti-inflammatory drugs block ethanol neuroimmune activation, inhibition of neurogenesis and neurotoxicity. The hypothesis that neuroimmune gene induction underlies addiction and affective disorders creates new targets for therapy.
This study was supported by NIH and NIAAA.