ETHANOL (a.k.a. ethanol / ethyl or grain alcohol (CH3CH2OH)) : a primary alcohol existing as a transparent, colorless, volatile, flammable liquid, miscible with water, methanol, ether, chloroform and acetone; it is formed by microbial fermentation of carbohydrates or by synthesis from ethylene
Epidemiology : lifetime prevalence of alcohol abuse and alcohol addiction (alcoholism) in USA is 5-10% for men and 3-5% for women. According to a new report from the World Health Organization (WHO), the harm caused by alcohol nearly equals that from smoking. Add in the social consequences of drinking, including wrecked families and lost days at work, which were excluded from the WHO report, and alcohol should arguably be the greater concern. Although a handful of researchers still question the idea that moderate drinking is beneficial, the consensus from epidemiological studies is that alcohol can improve health if taken in small doses - primarily by reducing the risk of heart attacks in older people. Bombarded by stories in the media portraying the medicinal effects of moderate consumption - but with no consistent message on what defines moderation - too many of us like to take much more than one drink, many valuing alcohol as a social lubricant and reliever of stress. The health benefits of alcohol are largely limited to a few individuals : since 1970, studies from all over the world have shown that moderate alcohol intake - 1-2 drinks a day - lowers the risk of coronary heart disease by 20-30% for older men and womenref. Today, the idea that moderate drinking can be beneficial to health is well established. But in the 1980s and 1990s, some sceptics suggested that this effect might be a statistical mirageref. Teetotallers, they argued, include ex-alcoholics, the elderly and ill. So the apparent health benefits of moderate drinking could in fact be an artefact. Some epidemiologists still wonder whether abstainers' relatively poor health is linked to some factor not directly related to their rejection of alcohol. But more recent epidemiological analyses have adjusted, so far as is possible, for confounding effects, and still find health benefits from moderate drinkingref1, ref2. They are backed by studies showing that alcohol benefits the body by boosting levels of 'good' cholesterol and blood proteins that are signs of a healthy heartref.

Another issue that has mostly been laid to rest is that wine is better than beer or spirits - a phenomenon labelled the 'French paradox' because it was thought to explain why citizens of this nation tend to escape heart disease despite an artery-clogging diet. Among many studies contradicting this idea, one of Czech beer drinkers found that those who imbibed four to nine litres each week had the lowest risk of heart disease, compared with those who drank more or lessref. The remaining debate is over what constitutes a healthy pattern of drinking. Seven drinks a week can be supped one per day with dinner or downed together in a Friday night. The weight of studies suggests that binge drinking in this way does not protect from heart disease in the same way as spreading it out over several daysref. Even small amounts of alcohol increase the risk of injury and boost the chances of developing about 60 diseases, including several cancers, liver cirrhosis and neuropsychological disorders. When these are fed into the epidemiological equation, only men over the age of 45 and women over 55 seem to lower their overall health risks by moderate drinkingref. Translated into guidelines for sensible drinking, this means that a middle-aged teetotal man, with high cholesterol or a family history of heart disease, would probably benefit by including a single drink a day with dinner. He might, however, achieve the same or better payback by starting to exercise or adopting a healthier diet. And for older people already following an exemplary lifestyle, the benefit reaped from a daily drink is probably marginal. Those in their 20s and 30s, meanwhile, may start accruing heart benefits from a daily drink, but at this age the threat of accidental injury equals the negligible risk from heart disease, so even moderate drinking seems to offer little payback. Another difficulty in conveying advice on healthy alcohol consumption is the lack of a standard definition for 'a drink'. The alcohol content of any drink varies with its volume and alcohol concentration, so that guidelines advocating a 'moderate' intake are often inconsistent within and between countries : a December 2003 report from the International Center for Alcohol Policies in Washington DC revealed that a 'standard' drink in Britain contains 8 grams of ethanol, in the United States it contains 14 g and in Japan 19.75 g. After a 1991 edition of the US TV programme 60 Minutes on the health benefits of wine, trade magazines reported a hike in the next month's wine sales of more than 40%. In part, the soft ride given to alcohol may be linked to the fact that the media and other influential sectors of society (politicians) tend to be drinkers. The alcohol industry has also tried hard to disseminate the virtues of its products. In the mid-1990s, the US wine industry proposed bottle labels advertising the health benefits of moderate drinking. Some labels appeared but were quickly abandoned when the US Bureau of Alcohol, Tobacco, Firearms and Explosives provisionally banned such statements in 1999. Industry representatives argue that they promote responsible drinking by broadcasting or contributing to public-health campaigns. At the same time, they acknowledge that the medical evidence on alcohol's health benefits has helped them persuade policy-makers of their product's appeal. > 75% of US healthcare providers did not define moderation in accordance with national guidelines. Internationally, the highest disease load attributable to alcohol is found in the heavy-drinking former socialist countries of Eastern Europe and in Latin America. Rich developed countries have the next biggest problem, with public-health experts being especially worried about binge drinking among the young. Trends differ from country to country - consumption is rising in Britain, for instance, but falling in France and Italy. In most developing countries, alcohol consumption is still relatively low, but it is climbing steeply, particularly in Asia, driven by economic growth and aggressive marketing.

In Britain - where overall alcohol consumption has risen by 50% since 1970. More forceful measures to curb consumption, e.g. raising the minimum legal drinking age, cutting the number of liquor shops, and restricting advertising and the hours during which drink can be sold work. Perhaps unsurprisingly, the price of alcohol has a very powerful influence on total consumption.

The 1985 Mikhail Gorbachev's government move to clamp down on the production of illegal alcohol slashed consumption from 14.2 to 10.5 litres of pure alcohol per person per year - and is estimated to have cut the number of alcohol-related deaths from accidents, poisoning and violence by 11% over 5 yearsref. But in present-day Russia, alcohol consumption and related mortality have climbed back to pre-1985 levels. In a one-party state the Soviet leaders didn't have to worry too much about a public backlash. But few democratic politicians are keen to impose higher taxes on alcohol and restrict its sale - there are few votes to be gained, and many potentially to be lost, from such actions : the key to success, the academy's report argued, will be to make the public more aware that measures to restrict the sale of alcohol and increase its price can relieve the unwanted consequences of excessive drinking, including violent crime. Sometimes problems have to escalate before WHO is convinced to do something drastic against industry. The Dietary Guidelines for Americans, published by the US government, recommends < 1 drink a day for women and 2 for men (1 drink is defined as 12 ounces (355 ml) of beer, 5 ounces (148 ml) of wine or 1.5 ounces (44 ml) of spirits). For young people, drinking even a small amount of alcohol could increase the chances of developing heart disease. The finding contrasts with the widely held view that drinking in moderation - around 2 drinks per day for men and one for women - can help protect against heart disease. Researchers are confident that this holds true for people who are over about 55 and at risk of heart disease. But they are unclear whether the health benefits of alcohol begin to accrue early in life - or exactly what alcohol is doing in the body to produce its beneficial effects. Using data from an ongoing study on heart disease, the hearts of > 3,000 people aged 33-45 years were probed using a CAT scanner. They searched for one of the earliest signs of heart disease - a hardening of coronary arteries - and then matched this up with information collected between 1985 and 2001 on how much each person drank. The more a person imbibed, the greater their likelihood of showing artery hardening. Those who had > 14 drinks per week, for example, were twice as likely to have artery problems than those who drank < 6. This result is at odds with a commonly found pattern in other studies on alcohol and heart disease, in which those who drink moderately have a lower risk of problems than both teetotallers and those who drink heavilyref. The finding implies that drinking alcohol early in life does not rack up gradual benefits that will protect drinkers later on. Instead, it backs the idea that a slug of liquor protects against heart disease in older people in a different way: by having almost immediate effects. It may, for example, cut the risk of a blood clot forming and choking off an artery. Binge drinking, defined as > 5 drinks at one time, is harmful. Indeed, the researchers found it difficult to tell whether younger people who drank more were harming their arteries because of the total quantity they drank or because they tended to drink in binges. Both probably contribute. The study is one of the first and largest to look in detail at the effects of alcohol on a young age group, in which the signs of impending cardiovascular problems are difficult to pick up. Most research has concentrated on older groups in which scientists can track more easily how many are struck by disease. Public-health experts already believe that young drinkers gain little by drinking at a young age. Any positive effects on the heart are thought to be outweighed by the increased risk of cancer, accidents and injuries. It might not be a good thing to recommend any alcohol. It will be difficult to pin down at what age the benefits of alcohol start to outweigh the risks. It could be done by examining those who take up drinking later in life, but very few people do this. Meanwhile, public-health experts recognize that young people are unlikely to give up drinking because of seemingly remote risks of disease. So they say that standard advice still holds: if you are going to drink, do so in moderation.
Aetiology : GABRG3 SNPs are linked with the risk of becoming an alcoholic. A gene that helps flies deal with stress also makes them tolerant to repeated alcohol intake : humans probably have a similar gene, which could help to explain some cases of alcoholism and possibly even lead to a treatment. High alcohol tolerance, the ability to resist the effects of alcohol after continued drinking, is one of the factors that can lead to alcohol dependence and addiction : highly tolerant people tend to drink more than others simply because they don't get the same kick from a given dose. Both tolerance and the tendency to develop alcoholism are known to be partly inherited. But only a few of the genes responsible have been identified. Because genetic studies in humans are difficult, Ulrike Heberlein's team at the University of California in San Francisco turned to the fruit fly Drosophila melanogaster. To measure ethanol tolerance in flies, the researchers placed the flies in a column containing several platforms. When they were exposed to ethanol vapour, the flies tended to lose their balance and fall off their platform to the next one down, until they finally landed with a drunken bump at the bottom of the column. The sooner the flies hit the bottom, the drunker they were. The researchers checked the ethanol tolerance of tens of thousands of flies whose genomes had been damaged at random locations. Normal flies took about 20 minutes to reach the bottom of the column. When the researchers exposed the same flies to a repeated dose of ethanol 4 hours later, the flies had developed a tolerance against the ethanol and took 8 minutes longer to hit the bottom. But mutants lacking a gene dubbed hangover reached the bottom of the column just 23 minutes after exposure to the second dose : this indicates that hangover mutants have a lower toleranceref. The mutant flies also died younger and coped less well than normal flies with other kinds of stress, such as excessive heat. The hangover gene codes for a type of protein that turns on other genes. Humans have many genes like this, making it likely that one of them is equivalent to hangover.It might turn on genes that activate the cellular response to stress. Humans probably have the equivalent gene : a similar gene is switched on in mice when they are given alcohol. It's nice to see that these things seem to be parallel in different organisms. Hangover is the second known gene responsible for ethanol tolerance. In 2000 Heberlein's group showed that a gene for a neurotransmitter called octopamine, which helps flies memorize rewarding experiences, is also importantref. Flies lacking both these genes have almost no alcohol tolerance. Such genes could be used to help identify people at risk of becoming alcoholics. The ultimate goal is to identify potential drug targets to treat alcoholism. Once you understand how tolerance works, you can potentially interfere with it pharmacologicallyref.
Pathogenesis : absorption (80% in duodenum and jejunum; 20% in stomach and colon; faster during starvation, accelerated gastric emptying (water, cholinergic drugs, hypoglycemia, gastroresection, ..), CO2-added drinks and if 15 < ethanol < 30%, slower during sugar-rich meals, physical or mental effort, hypothermia); ethanol ==
1) ==+ NAD+ alcohol dehydrogenase (ADH)==> NADH + H+ +
2) ==+ NADP+ + FAD + H+ + MEOS==>NADP+ + H+ + FADH2 + cyt P450 +
3) ==+ 2O2- + 2 H+ + SOD== H2O2 + O2 == + 2H2O2catalase==> 2H2O + O2 +
4) ==+ OH- ==> CH3CHOH ==> Such reactions occur mainly in liver (85-90%), but also in monocytes, histiocytes, myocytes and gastric cells (less expressed in females). R.O.S. produced in 3) and 4) cause peroxidation in membrane lipids, alteration in mitochondria (=> megamitochondria), alterations in microtubules (=> ballooned cells (showable by Masson trichromic staining) and eosinophilic Mallory bodies (detected by van Gieson staining)). Protein adducts are immunogen and cause hypersensitivities => fibrosis : perisinusoidal => perivenular => pericellular (a1-FP-producing rosette of 7÷8 cells arranged in 2 strands). A normal dose of alcohol is metabolized mainly by ADH (90%), MEOS (8%) and SOD+catalase (2%). During chronic intoxication alcohol is metabolized mainly by ADH (50%) and MEOS (50%). 8% of absrobed ethanol is conjugated to glucuronic acid. 2% is eliminated through respiration, urine and skin. While ethanol concentration in expirated air is proportional to alcoholemia, alcoholuria is not.
Toxicity relates to V/Dt, ADH3*1, ALDH2*1, HLA-A1, HLA-B40 and overactive SLO-1 / BK (a potassium channel that regulates nerve firing in Caenorhabditis elegans). In vitro, ethanol stimulates adenosine signaling by inhibiting SLC29A1 / type 1 equilibrative nucleoside transporter (ENT1), whereas chronic ethanol exposure downregulates ENT1. In vivo ENT1 has a physiological role in ethanol-mediated behaviors and decreased A1 adenosine receptor function promotes alcohol consumptionref
Roughly 80% of alcohol-dependent individuals report smoking tobacco regularly : the combined effects of alcohol dependence and chronic smoking are associated with greater regional brain damage than chronic alcoholic drinking or smoking alone, an effect most prominent in the frontal lobes. Cigarette smoking, independent of alcohol consumption, also has adverse effects on neuronal viability and cell membranes in the midbrain and on cell membranes of the cerebellar vermis, and associated with lower N-acetylaspartate levels in lenticular nuclei and thalamusref
Clearance : pulmonary, renal, and cutaneous
TLV : 1,000 ppm
Ethanol content in different drinks : Favorable effects : resveratrol in wine may inhibit oxidation of LDLs => reduced rissk of acute myocardial infarction (AMI)ref (RDA 35-40 g/day for males and 23-28 g/day for females)
Symptoms & signs : Laboratory examinations : approximately 20% of patients seen in clinical practice have an underlying alcohol-use disorderref Antidipsotropic therapy : Illegal and surrogate alcohol products consumed in Estonia. The initial source of information was a series of visits made in August 2005 to a soup kitchen in central Tartu, Estonia. Individuals were asked for brief details of their personal circumstances, what they normally drank, and in addition they were asked to bring samples of the substances they usually consumed. In other cases, the substances identified were purchased by the investigators or from informal contacts in northeastern part of Estonia, an area that is well known for illegal alcohol consumption. Samples were tested for chemical contents. We identified a range of alcohol-containing substances that are consumed, although, not intended for consumption. These comprised medicinal products, after-shaves, illegally produced spirits, and fire-lighting fuel. The medicinal compounds contained, on average, 67% ethanol by volume; the after-shaves contained slightly less. Both were typically pure, with a few containing detectable quantities of isoamyl alcohol. The illegally produced alcohol contained, on average, 43% ethanol by volume, ranging from 32-53%. However, many also contained detectable quantities of long chain alcohols. These substances are half the price or less of commercial vodka, with fire lighting fuels especially inexpensive. Conclusions: There is in Estonia a range of alcohol-containing substances easily available at low cost. Some contain substantially higher concentrations of ethanol than commercial spirits and others also contain toxic long chain alcoholsref

See also Italian laws
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