Wine IS Medicine

Georges M. Halpern, MD, PhD

Distinguished Professor of Pharmaceutical Sciences

Hong Kong Polytechnic University drgeorges@drgeorges.net

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Disclaimer
This presentation is exclusively prepared for education and information. It was not supported by any commercial company, or wine industryrelated institution. All references are available on PubMed/Medline (National Library of Medicine). I do not support, encourage or condone alcoholism, or any form of abuse of wine.

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What is Wine?
German JB, Walzem RL. The health benefits of wine. Annu Rev Nutr 2000;20:561-593

The term wine describes a diverse commodity class composed of the yeast fermentation products of the must, or juice, pressed from grapes, the fruit of genus Vitis. Wine is a fruit product, but fermentation produces a variety of chemical changes in the must, and so wine is not simply grape juice with ethanol added. Fermentation alters the must by altering the conjugation of organic acids and phenolics, by extraction and formation of copigments and the development of an anaerobic and protective redox potential.
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Wine & Ethanol

German JB, Walzem RL. Annu Rev Nutr 2000;20:561-593

Wine contains 8-15% ethanol by weight. The effects of ethanol on overall mortality in modern western populations follow a J-shaped curve. In such a relationship, moderate ethanol intakes produce a significant reduction in mortality relative to abstinence from ethanol, but, beyond moderate intakes, mortality rises sharply.

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Is Wine Different from Other Alcoholic Beverages?

Burns J, Crozier A. Lean ME. Alcohol consumption and mortality: is wine different from other alcoholic beverages? Nutr Metab Cardiovasc Dis 2001;11:249-258.

Both clinical and experimental evidence suggest that red wine offers greater protection to health.; this is attributed to grape-derived antioxidant polyphenolics found particularly in red wine.
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Composition of Wine
Excluding Phenolic Acids and Polyphenols
Concentration (g/100ml) Water 80-90 Carbohydrates/sugars 0.2-0.45 Alcohols (mostly ethyl) 8.0-15.3 Glycerol 0.30-1.40 Aldehyde 0.01-0.050 Organic Acid (e.g. tartaric, etc.) 0.3-1.10 Nitrogenous compounds 0.01-0.09 Mineral Compounds (K, etc.)HK PolyU 23/02/05 0.15-0.40 6 Component

Summary of Phenolic Acid and Polyphenol Components of Red and White Wines
Concentration (mg/L)

Component
Nonflavonoids:
Hydroxybenzoic acids, Hydroxycinnamic acids, Stilbenes

Red Wine 240-500

750-1060

White Wine 160-260

25-30

Flavonoids: Flavonols,
Flavanols, Anthocyanins

Total phenolic acids and polyphenols

1200 (900-2500)
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200 (190-290)
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The Antioxidant Activity in 1 Glass of Red Wine (150 ml) is Equivalent to that Found in:
12 glasses of White Wine 2 cups of Tea 5 Apples 5 (100g) port. of Onion 5.5 port. of Eggplant 3.5 gl. of Black Currant juice 500 ml of Beer 7 glasses of Orange juice 20 glasses of Apple juice

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Pharmacokinetic Parameters of Wine and Food Flavonoids

Quercetin Parameter Dose (mg) E1/2(h) Tmax(h)
Cmax(mmol liter-1) Fried Onions Apples

Epicatechin
Nestl Nestl Noir 40g Noir 80g

Catechin
Wine Ethanol Wine + Ethanol

68 28 0.7 740

98 23 2.5 300

82 1.9 2.0 355

164 2.3 2.6 675

35 3.8 1.5 81

35 3.1 1.5 91
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The ONLY Thing that Improves with Age is Wine!

Burns J, Gardner PT, Matthews D, et al. Extraction of phenolics and changes in antioxidant activity of red wines during vinification. J Agriic Food Chem 2001;49:5797-5808.

4 wines were tested. 9 days after vinification the total phenolic content was comparable to the one of a bottled wine, but the antioxidant activity, due to larger polyphenolics that appear during aging, was significantly lower.
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Catechin is Present as Metabolites in Human Plasma after Consumption of Red Wine

Donovan JL, Bell JR, Kasim-Karakas S, German JB, Walzem RL et al. J Nutr 1999;129:1662-1668

Catechin is present almost exclusively as metabolites in plasma after consumption of red wine. Flavonoids are extensively conjugated after absorption from foods; it is the metabolites, and not the forms that exist in foods, that require attention.
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Catechins from Red Wine are Absorbed and Excreted, Regardless of Alcohol Content
Donovan JL, Kasim-Karakas S, German JB, Waterhouse AL. Urinary excretion of catechin metabolites by human subjects after red wine consumption. Br J Nutr 2002;87:31-7.

Catechin in all urine samples was present as metabolites, without differences between red wine and dealcoholized red wine (120 ml/day).

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Red Wine >White Wine on Platelets

Pignatelli P, Lenti L, Pulcinelli FM, et al. Red and white wine differently affect collagen-induced platelet aggregation. Pathophysiol Haemost Thromb 2002;32:356-358.

20 healthy subjects randomly consumed 300ml/day x 2w of red or white wine (same % ethanol). At +2w, red wine subjects had lower response to platelet agonist (p<0.005). This is probably due to the higher concentration in polyphenols in red wine.
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Consumption of Red Wine with Meals Reduces the Susceptibility of Human Plasma and LowDensity Lipoprotein to Lipid Peroxidation
Fuhrman B, Lavy A, Aviram M. Am J Clin Nutr 1995;61:549-554

Red wine consumption [400 mL/day x 2 wk] resulted in 20% reduction of plasma lipid peroxidation (TBARS), reduced LDL lipid peroxidation (Cu ions), and prolonged the lag phase required for LDL oxidation. White wine consumption resulted in 34% increase in plasma lipid peroxidation, and 41% increase of LDL lipid peroxidation. Vitamin E or beta-carotene did not change; red wine polyphenols were elevated in plasma and LDL.
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Red Wine Protects Against Cigarette

Papamichael C, Karatzis E, Karatzi K et al. Red wines antioxidants counteract acute endothelial dysfunction caused by cigarette smoking in healthy nonsmokers. Am Heart J 2004;147:274.

Acute smoking of 1 cigarette in 16 healthy volunteers caused a reduction in flowmediated dilatation (p<.001). Simultaneous ingestion of red wine or dealcoholized red wine abrogated this effect on FMD, and harmful effects on endothelium.
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Drink Wine With Meals

Trevisan M, Schisterman E, Menotti A et al. Drinking pattern and mortality: the Italian Risk Factor and Life Expectancy pooling project. Ann Epidemiol 2001;11:312-319

8647 men and 6521 women, age 30-59 at baseline were followed for 7 years. Drinkers of wine outside meals exhibited higher death rates (all causes, non CV, cancer) as compared to drinkers of wine with meals.
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Red Wine vs. High-fat Meals

Ventura P, Bini A, Panini R, Marri L, Tomasi A, Salvioli G. Red wine consumption prevents vascular oxidative stress induced by a high-fat meal in healthy volunteers. Int J Vitam Nutr Res 2004;74:137-43.

Ingestion of red wine during a high-fat meal significantly reduces oxidative stress without inducing any significant modification in postprandial lipemia.

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Copenhagen City Heart Study

Gronbaek M et al. BMJ 1995;310:1165-1169

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Copenhagen City Mortality Study

Gronbaek M et al. Ann Intern Med 2000;133:411-419

During 257 859 person-years of follow-up, 4833 participants died. Wine drinkers had significantly lower mortality from both coronary heart disease and cancer than did non-wine drinkers (p=0.007 and p=0.004, respectively). Wine intake may have a beneficial effect on allcause mortality that is additive to alcohol. This effect may be attributable to a reduction in death from both coronary heart disease and cancer.
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Does Wine Work?

Goldberg D. Clinical Chemistry 1995;41:14-16

If every North American drank 2 glasses of wine each day, cardiovascular disease, which accounts for almost 50% of deaths in this population, would be cut by 40%, and $40 billion could be saved annually.

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Wine beats Valium

Paladini AC et al. Flavonoids and the CNS: from forgotten factor to potent anxiolytic compounds. J Pharm Pharmacol 1999:51;519-526

Some natural occurring wine flavonoids, e.g. chrysin and apigenin, selectively bind with high affinity to the central benzodiazepine receptor, and exert powerful anxiolytic effects.

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Wine Protects the Brain of the Elderly

Orgogozo JM, Dartigues JF, Lafont S et al Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area.Rev Neurol [Paris] 1997;153:185-192

3777 community residents 65 y were enrolled; 3 y later 2273 subjects were studied. 318 drank 250-500ml/d of wine; OR was 0.18 for incident dementia (p<0.01) and 0.25 for Alzheimers (p<0.03) when compared to 971 non-drinkers. There is no medical rationale to advise people >65 to quit drinking wine moderately.
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Wine Sharpens Your Brain!

Britton A, Singh-Manoux A, Marmot M. Alcohol consumption and cognitive function in the Whitehall II study. Am J Epidemiol 2004;160:240-247

Increasing levels of alcohol (mostly wine) consumption (>240g/week) in middle-aged subjects (4,272 , 1761 ; 46-68y) were associated with better cognitive function: memory test, AH4, Mill-Hill, phonetic and semantic fluency. The effect was stronger for women, and not explained by confounding factors.
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Ceriello A, Bortolotti N, Motz E, et al. Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation: a pleasant approach to the prevention of cardiovascular disease in diabetes. Eur J Clin Invest 2001;31:322-328.

A Pleasant Way to Protect Diabetics: Red Wine

Some of the symptoms of diabetes are: Frequent urination Excessive thirst Extreme hunger Unusual weight loss Increased fatigue Irritability Blurry vision

Free radicals are produced in the absorptive phase, with reduced serum antioxidant capabilities, LDL oxidation, and activation of coagulation. Moderate consumption of red wine, during a meal, preserves plasma antioxidation and reduces both LDL oxidation and thrombotic activation, in diabetics.
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Wine and Retina

Obisesan TO, Hirsch R, Kosoko O, et al. Moderate wine consumption is associated with decreased odds in developing age-related macular degeneration in NHANES-1. J am Geriatr Soc 1998;46:1-7

In a study of >3,000 adults, alcohol consumers (wine drinkers in particular) were found to be at reduced risk for AMD. The effects of wine as antioxidant, and on platelet aggregability are associated with reducing the odds of developing AMD.

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Wine and Gallstones in Italy

Attili AF, Scafato E, Marchioli R, Marfisi RM, Festi D. Diet and gallstones in Italy: the crosssectional MICOL results. Hepatology 1998;27:1492-1498

After analyzing data from >15,000 men and >13,000 women, they observed a decreasing risk of GS and increasing serum HDL levels by increasing daily wine consumption.

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Antibacterial Activity of Wine vs. Salmonella enteritidis: pH or alcohol?

Marimon JM, Bujanda L, Gutierrez-Stampa MA, et al. J Clin Gastroenterol 1998;27:179-180

Red wines bactericidal effect was large and greater than the same ethanol concentration at the same pH. Polyphenols may well have a bactericidal effect.
[The same group confirmed bactericidal
effect vs. H. Pylori. AJG 1998;93:1392]

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Wine not Beer or AlcoholProtects vs. Common Cold

Takkouche B, Regueira-Mendez C, Garcia-Closas R, et al. Intake of wine, beer, and spirits and the risk of clinical common cold. Am J Epidemiol 2002;155:853-858.

When drinkers of >14 glasses of wine/week were compared to teetotalers, the r risk was 0.6. Wine intake (red wine) may have a protective effect vs. common cold, while beer, spirits and total alcohol intake did not affect the incidence.
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Wine as Digestive Aid

Weisse ME, Eberly B, Person DA. BMJ 1995;311:1657-1660

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Wine as a Digestive Aid

Weisse ME, Eberly B, Person DA. BMJ 1995;311:1657-1660

Undiluted red and white wine, and bismuth salicylate (Pepto-Bismol) were both effective in reducing the number of viable Salmonella, Shigella, and Escherichia coli (by 105-106 CFUs) after 20-30 minutes. Dilutions of wine were much more effective in decreasing colony counts than were similar dilutions of bismuth salicylate. The antibacterial property of wine is largely responsible for wines reputation as a digestive aid.
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Red Chilean Wines Kill H. pylori

Daroch F, Hoeneisen M, Gonzalez CL, et al. In vitro antibacterial activity of Chilean red wines against Helicobacter pylori. Microbios 2001;104:79-85.

16 Chilean red wines (Cabernet Sauvignon, Cabernet Merlot, Cabernet Organic & Pinot noir), and the active extracts of 2 randomly selected wines did demonstrate antibacterial activity vs. 6 strains of H. Pylori isolated from gastric biopsies. Activity depended mainly on resveratrol.

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Wine, Osteoporosis and Hip Fracture

Hoidrup S, Gronbaek M, Gottschau A, Lauritzen JB, Schroll M. Am J Epidemiol 1999;149:9931001

Research included 32,000 patients. A light to moderate alcohol intake does not influence the risk of hip fracture. Preferrers of wine tend to have a lower risk of hip fracture as compared to preferrers of other alcoholic drinks.

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Resveratrol vs. Human Breast Cells

Mgbonyebi OP, Russo J, Russo IH. Antiproliferative effect of synthetic resveratrol on human breast epithelial cells. Int J Oncol 1998;12:865-869

The effect of resveratrol is consistent with the activity of other anticancer drugs. It is a potential chemopreventive agent for both hormone responsive and nonresponsive breast cancers.
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Suppression of Aromatase by Red Wine

Eng ET, Williams D, Mandava U, et al. Suppression of aromatase (estrogen synthetase) by red wine phytochemicals. Breast Cancer Res Treat 2001;67:133-146.

Aromatase converts androgen to estrogen, hence promoting proliferation of breast cancer cells. Red wine was shown to be much more effective than white wine in suppression of aromatase. This was demonstrated in different cell models, and in a model of transgenic mouse in which aromatase is over-expressed in the mammary tissue.
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Resveratrol and Quercetin Modulate Oral Cancer Cell Growth

El Attar TM, Virji AS. Modulating effect of resveratrol and quercetin on oral cancer growth and proliferation. Anticancer Drugs 1999;10:187-193

Resveratrol or a combination of resveratrol and quercetin, in concentrations equivalent to that present in red wines, are effective inhibitors of oral squamous carcinoma cell growth and proliferation.

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Intake of Wine is Associated with a Reduced Risk of Lung Cancer

Prescott E, Gronbaek M, Becker U, Sorensen TI. Alcohol intake and the risk of lung cancer: influence of type of alcoholic beverage. Am J Epidemiol 1999;149:463-470

Data from 3 prospective studies of >28,000 subjects confirmed that intake of wine was associated with a reduced risk of lung cancer. This seemingly protective effect may be related to the antioxidant properties of wine.
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Red Wine, but not White Wine Decreases the Risk of Lung Cancer
Ruano-Ravina A, Figueiras A, Barros-Dios JM. Type of wine and risk of lung cancer: a case-control study in Spain. Thorax 2004;59:981-5

In 1999-2000, a study was conducted on 319 subjects (132 cases, 187 controls). A slight but significant (OR 1.2/each daily glass) was observed between lung cancer and white wine consumption. But red wine had an inverse association (OR 0.87).
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Wine Does Not Increase the Risk of Prostate Cancer

Sesso HD, Paffenbarger RS Jr, Lee IM. Alcohol consumption and risk of prostate cancer: The Harvard Alumni Health Study. Int J Epidemiol 2001;30:749-755

7612 Harvard alumni (~66.6y) were prospectively followed from 1988 through 1993; 366 cases of prostate cancer occurred. Liquor, but not wine or beer, consumption was positively associated with prostate cancer
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Polyphenols in Red Wine Impair Prostate Cancer Cell Line

Romero I, Paez A, Ferruelo A, Lujan M, Berenguer A. Polyphenols in red wine inhibit the proliferation and induce apoptosis of LANCaP cells. BJU Int 2002;89:950-954.

Quercetin, rutin, morin, gallic acid and tannic acid, from red wine, inhibited the growth of prostate cancer LANCaP cells at different concentrations, and induced apoptosis.

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Beethoven Should Have Drunk Wine!

Becker U, Gronbaek M, Johansen D, Sorensen TI. Lower risk for alcohol-induced cirrhosis in wine drinkers. Hepatology 2002;35:868-875.

Individuals who drank >5 drinks/day had a relative risk of 14-20 for developing cirrhosis. If wine was 16-30% of total intake, risk was 0.4; if wine was >51%, risk was 0.3. Compared to beer and spirits, wine carries a much lower risk.
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Wine is Safe for Asthmatics

Two studies Halpern GM et al. Ann Allergy 1985;55:686-69; Vally H et al. J Allergy Clin Immunol 1999;103:41-46 have confirmed that consumption of wine with normal levels of sulfites is safe in most asthmatics. Only a very limited number of exquisitely sensitive patients may suffer, mostly after very high exposure to sulfites. Histamine content does not influence wine tolerance in normal subjects Kanny G et al. Allergie & Immunologie 1999;31:45-47. No [n=8] subject reacted after ingesting wine, rich or poor in histamine. There were no changes in plasma histamine, nor in plasma or urinary methyl histamine. The amount of histamine in wine has no clinical or biological effect in healthy subjects.
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Moderate Drinking During Pregnancy: Cause for Concern?

Abel EL. Clinica Chemica 1996:246:149154

Weighing the issues, the greatest danger to the life of an unborn child does not come from a drink per day but from alarmism over what might be the harm to the child, which could result in termination of an otherwise healthy pregnancy, or psychological distress that might itself lead to an unhealthy pregnancy.
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Wine Drinkers are Smarter and Richer

Mortensen EL, Jensen HH, Sanders SA, Reinish JM. Better psychological functioning and higher social status may largely explain the apparent health benefits of wine: a study of wine and beer drinking in young Danish adults. Arch Intern Med 2001;161:1844-1848

In 363 men and 330 women aged 29-34, wine drinking was significantly associated with higher IQ, parental educational level, and socioeconomic status. Beer drinking was associated with significantly lower scores. Wine drinking is a general indicator of optimal, social, cognitive, and personal development.
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Drink your Bordeaux in <90

Lupi-Pegurier L, Muller M, Leforestier E, Bertrand MF, Bolla M. In vitro action of Bordeaux red wine on the microhardness of human dental enamel. Arch Oral Biol 2003;48:141-145

Wine has no disastrous effect on the microhardness (Vickers; scanning electron microscopy) of dental enamel if contact is <90 s. When exposure is >120 s, the decrease in the microhardness of enamel was significant (P<0.05).
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The Champagne Angle

Pemberton PL, Calder I, OSullivan C, Crockard HA. The Champagne angle. Anaesthesia 2002;57;402-403.

The cranio-cervical extension required to drain a glass of wine was 40 with a narrow flute, 22 with a wide flute, 26 with a wine glass, and 0 with a champagne saucer. The narrow flute requires 73% of the total available cranio-cervical extension.

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Cork Injury to the Eye

Cavallini GM, Lugli N, Campi L, Pagliani L, Saccarola P. Bottle-cork injury to the eye: a review of 13 cases. Eur J Ophthalmol 2003;13:287-291

Bottle-cork injuries account for 10.8% of post-trauma admission in Modena. Most are due to sparkling white wine served at room temperature. There is no correlation between ocular injury and the eyebottle distance or the type of cork.

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Enjoy in the Right Shape of Glass

Huttenbrink KB, Schmidt C, Delwiche JP, Hummel T. The enjoyment of red wine is influenced by the shape of the wine glass. Laryngorhinootologie 2001;80:96-100.

Egg-shaped glasses, compared to tulip or beaker glasses, appear to produce higher intensity and higher complexity of wine odors.
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Wine May Make you Live 10 More Years!

Howitz KT, Bitterman KJ, Cohen HY, Lamming DW et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003 Aug 24 [Epub ahead of print]

Resveratrol, a potent activator of sirtuins, lowers the Michaelis constant of SIRT1 (a human deacetylase) and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. Resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by70%!
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Salute!
Cheers! Sant! Salud! Skl!
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