Letteratura scientifica selezionata sul tema "Alcohol-related brain damage"

Long-term heavy alcohol consumption causes significant brain abnormalities and impairs cognitive functioning. A number of terms have been used to describe these effects, including: ‘alcohol-related dementia’, ‘alcohol-induced dementia’, and ‘alcoholic dementia’. The more pragmatic umbrella term ‘alcohol-related brain damage’ (ARBD) is also used. The literature is beset with limitations, in particular the lack of a diagnostic gold standard, and the difficulty in making a clinical diagnosis. Many individuals labelled as having an alcohol-related dementia are, in fact, suffering from the Wernicke–Korsakoff syndrome (WKS). (This is a specific neuropathological disease caused by thiamine deficiency, which can occur secondary to alcohol misuse. It is considered in Chapter 4.1.12.) When considering the topic of ‘alcohol-related dementia’ it is probably sensible to take a broad clinically-based diagnostic view that includes both WKS and other cases of ‘dementia’ that appear to be alcohol-related. Alcohol-related dementia should be recognized as a preventable condition. However, identification is hampered by a lack of clarity in terminology, and a lack of standardized and specialized screening instruments and assessment procedures. These individuals make repeated use of Accident and Emergency Departments, general medical, and long stay wards. Early identification would reduce their need for these services. Abstinence is the key to recovery. Treatment services should be integrated and flexible.

Like the liver, the brain is commonly affected by long-term alcohol misuse. While neurocognitive dysfunctions are widely known in their most extreme presentations, such as Korsakoff’s syndrome and Wernicke’s encephalopathy (WE), there are other less explicit manifestations of neurocognitive damage which occur more frequently. This chapter explores these conditions under the umbrella term ‘alcohol-related brain damage’ (ARBD), more specifically employing the term Wernicke–Korsakoff’s syndrome (WK) when referring to the acute and chronic effects of thiamine deficiency. The correlation between excessive alcohol consumption and thiamine intake is explored, along with the body’s response of boosting gamma-aminobutyric acid (GABA)–benzodiazepine and NMDA receptors. In acute and non-acute cases of ARBD, prompt diagnosis and treatment are essential due to the risk of long-term cognitive and intellectual damage it can yield. As such, psychosocial treatment in the aftermath of the clinical phase is equally important, focusing on assessment, therapeutic intervention, adjustment, and social integration.

Alcohol is one of the most frequently used substances, and alcohol-related disorders are common, especially in western societies. While there is no safe lower drinking level, a clear dose–response relationship has been shown between alcohol intake and organ damage. Conceptualization and diagnostic classification of alcohol use disorders have changed over time, focusing most recently on aspects of craving, loss of control, and continued use despite negative consequences. Alcohol acts via various binding sites in the brain and via downstream effects, including glutamatergic, GABAergic, serotonergic, dopaminergic, opioid, and neuroendocrine pathways. For its long-lasting, habit-forming effects, sensitization within the mesolimbic–mesocortical system is crucial. Psychological treatments traditionally focus on motivational enhancement, cognitive behaviour therapy, and the community reinforcement approach. Pharmacological treatment approaches range from aversive and reward-inhibiting to anti-craving compounds and cognitive enhancers, which target opioid, glutamatergic, and monoamine receptors. Improvement of treatment effects can be achieved by polypharmacy and use of personalized medicine, based on clinical characteristics, biomarkers, and genetic indicators.

Alcohol produces a range of central-nervous-system-related biological effects, including anxiety reduction, euphoria, sedation, disinhibition, aggression, blackouts, tolerance, addiction, and withdrawal. The Chinese have used alcoholic drinks since 5000 B.C. Presumably, man ventured to drink the liquid from fermented grain, liked the intoxicating effect, and started to make it on purpose. Alcohol has been used as an anesthetic for millennia (see chapter 7). Alcohol is indispensable in medicine as a solvent. Laudanum, a staple of the medicine chest in the nineteenth century, was simply an alcoholic solution of opium. NyQuil, a cough syrup, and Listerine, an oral antiseptic, all contain copious amounts of ethanol. Alcohol has beneficial effects when consumed in moderate amounts. Research strongly suggests that moderate consumption of alcohol, especially red wine and dark beer, seems to have protective effects on the heart. The hallmarks of the Mediterranean diet are olive oil and red wine, and people from such countries have fewer cardiovascular events. Flavonoids, the active principle in red wine, are thought to exert beneficial cardiovascular effects. According to the Bible (Genesis 9:20–21), Noah was the first man who discovered wine: “Noah, a man of the soil, was the first to plant a vineyard. When he drank some of its wine, he became drunk and lay uncovered inside his tent.” The New Testament gives an account of Jesus performing his first miracle—turning water into wine. Despite the beneficial effects of moderate alcohol consumption, excessive use of alcohol damages the brain, heart, and liver. Even mild drunkenness can cause temporary loss of memory. The liver metabolizes alcohol with an enzyme called alcohol dehydrogenase, which turns alcohol into acetaldehyde. Because acetaldehyde is acutely toxic, people—including many Asians—who lack alcohol dehydrogenase cannot tolerate much alcohol. This is the reason that their faces become flush when they drink alcohol and that there are fewer incidents of alcoholism in Asians. Alcoholism is known to cause psychosis and alcoholic dementia. To fight the “demon rum,” on January 16, 1919, the U.S. Congress passed the Eighteenth Amendment, prohibiting “the manufacture, sale, or transportation of intoxicating liquors.” It was repealed 14 years later, the only amendment to the U.S. Constitution that has been repealed.

Luigino Troisi of the University of Salento found (Tetrahedron Lett. 2010, 51, 371) that a variety of primary and secondary amines could be coupled with a benzylic halide 1 under carbonylating conditions. Ilhyong Ryu of Osaka Prefecture University showed (Organic Lett. 2010, 12, 1548) that under reducing conditions, an iodide 3 coupled with CO to give the primary alcohol. Felicia A. Etzkorn of Virginia Tech observed (Organic Lett. 2010, 12, 696) that under Hg hydrolysis conditions, the orthothioester derived from 5 coupled with 6 to give 7. Yasuharu Yoshimi of the University of Fukui and Minoru Hatanaka of Iwate Medical University devised (Tetrahedron Lett. 2010, 51, 2332) conditions for the decarboxylative addition of the acid 8 to 9 to give 10. Yong-Min Liang and Xiaojun Yao of Lanzhou University and Chao-Jun Li of McGill University described (J. Org. Chem. 2010, 75, 783) a related procedure with α-amino acids. Yasutaka Ishii of Kansai University established (J. Am. Chem. Soc. 2010, 132, 2536) that t -butyl acetate 12 was an effective partner for the Ir-mediated oxidation-coupling-reduction of an alcohol 11. He used (J. Org. Chem. 2010, 75, 1803) a similar protocol to condense acetone with the diol 14, to give the long-chain diketone 16. The formation of allylic Grignard reagents can be inefficient because the excess reactive halide tends to couple with the Grignard reagent as it forms. Brandon L. Ashfeld of the University of Notre Dame found (Tetrahedron Lett. 2010, 51, 2427) a simple solution to this problem: inclusion of a catalytic amount of the inexpensive Cp2 TiCl2 to mediate the addition of 18 to 17. Brian T. Connell of Texas A&M University demonstrated (J. Am. Chem. Soc. 2010, 132, 7826) that with Mn, 21 could be added to 20. The acetate 21 is thus an easily prepared homoenolate equivalent. Note that although 21 is an E/Z mixture, the product 22 is cleanly Z. Gérard Cahiez of the Université de Paris 13 reported (Synlett 2010, 299) a detailed study of the Cu-catalyzed coupling of 24 with 23. Without supporting ligands, slow addition (syringe pump, 1 h) of 24 to 23 assured clean formation of 25. Manual slow addition (dropping funnel, 15 min) was not effective.