Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the relationship between the polymorphism of aldehyde dehydrogenase (ALDH) isozyme and alcoholic liver injury, ALDH isozyme was analyzed by isoelectric focusing electrophoresis in hair roots from normal volunteers and alcoholics with chronic liver disease. Liver biopsy specimens from alcoholics and non-alcoholics with chronic liver disease were also analyzed. It was found that (1) the frequency of low Km ALDH isozyme in hair roots from chronic alcoholics with liver injury was 90%, which was significantly higher than those from normal volunteers (44%) and from non-alcoholics with chronic liver disease (56%); (2) the isozyme pattern of liver specimens analyzed coincided with that of hair roots; (3) the low Km ALDH isozyme-positive subjects including alcoholics showed no facial flushing, and negative subjects showed facial flushing after drinking alcohol. It is concluded that a much higher frequency of low Km ALDH isozyme was found in chronic alcoholics with liver injury. There was no apparent difference in hepatic biochemical and histological findings between chronic alcoholics with and without low Km ALDH isozyme, suggesting that acetaldehyde does not play a primary role in the pathogenesis of alcoholic liver injury.
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PMID:Low Km ALDH isozyme and alcoholic liver injury. 663 52

To test the suggestion that chlorpropamide-alcohol flushing (CPAF) resembles the disulfiram effect and might be mediated by acetaldehyde, the initial metabolite of alcohol, blood concentrations of acetaldehyde were measured after a drink of alcohol in controls and diabetics positive and negative for CPAF. The CPAF-positive diabetics had significantly greater blood acetaldehyde concentrations after alcohol than the CPAF-negative diabetics both with a single dose of chlorpropamide and after two weeks' chlorpropamide treatment. Concentrations in the CPAF-positive group after chlorpropamide were also significantly greater than after a placebo tablet. There was also a clear separation in the increase in facial temperature after two weeks of chlorpropamide between the CPAF-positive and CPAF-negative groups (although there was some overlap after a single tablet). There was no difference in plasma chlorpropamide or alcohol concentrations between CPAF-positive and CPAF-negative diabetics. These findings show that CPAF is distinct from alcohol flushing and that the acetaldehyde concentration in the blood provides an objective measure of CPAF. The difference between flushing and non-flushing diabetics cannot be accounted for by differences in blood concentrations of chlorpropamide or alcohol.
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PMID:Blood concentrations of acetaldehyde during chlorpropamide-alcohol flush. 679 82

Many diabetics who take chlorpropamide (a sulphonylurea compound) experience facial flushing after drinking even small amounts of alcohol. These flushers have a noticeably lower prevalence of late complications of diabetes (microangiopathy, macroangiopathy, and neuropathy) than non-flushers. This flush reaction is accompanied by increased blood acetaldehyde concentrations, suggesting an inhibition of aldehyde dehydrogenase activity. In the present study the activity of this enzyme in erythrocytes was assessed in the absence of chlorpropamide. Erythrocyte homogenates obtained from flushers and non-flushers were incubated with acetaldehyde and the rate of metabolism studies. Flushers eliminated acetaldehyde more slowly at a low range of concentrations (0--30 mumol/l), suggesting a difference in aldehyde dehydrogenase activity. Further studies are needed to clarify the role of this enzyme in the pathogenesis of diabetic complications.
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PMID:Chlorpropamide-alcohol flushing, aldehyde dehydrogenase activity, and diabetic complications. 681 Oct 34

Sixty three male Japanese, aged 20-40 yr were evaluated as to the degree of facial flushing following a controlled dose of ethanol either as Japanese rice wine or ethanol 0.4 g kg body weight. Thirty four subjects responded with overt facial flushing. The acetaldehyde levels in blood and expired air were significantly higher in the flushing group without a change in ethanol elimination rate. Urinary excretion of Vanilmandelic acid (VMA) and 3 methyoxy-4-Hydroxyphenylglycol (MHPG) are reported.
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PMID:Individual differences in blood and breath acetaldehyde levels and urinary excretion of catecholamines after alcohol intake. 700 32

4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, rapidly abolished the accumulation of acetaldehyde following alcohol ingestion both in volunteers pretreated with the Antabuse analog calcium carbimide and in an antabuse-treated alcoholic. 4-MP also attenuated other typical symptoms, including facial flushing and tachycardia, thus suggesting its usefulness in the acute treatment of severe disulfiram-alcohol reactions.
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PMID:The disulfiram (Antabuse)-Alcohol reaction in male alcoholics: its efficient management by 4-methylpyrazole. 703 Jan 8

Ethanol-induced facial flushing was measured in 30 men, aged 21 to 25, who had family histories of alcoholism and in 30 matched controls. The drug was administered as 0.75 ml of 95% ethanol per kilogram of body weight, mixed with a sugar-free soft drink and consumed over 5 minutes. Facial flushing was assessed over 90 minutes using both observational ratings and a plethysmograph. Family history positive (FHP) subjects demonstrated significantly higher levels of flushing than family history negative (FHN) controls on objective measures. Correlations with the flushing response were .83 for blood acetaldehyde, and at least .60 for heart rate and skin temperature. This is the first known demonstration in Caucasians of a possible association between flushing and blood acetaldehyde levels in individuals hypothesized to be at risk for the development of alcoholism.
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PMID:Alcohol-related flushing and the risk for alcoholism in sons of alcoholics. 711 36

Healthy volunteers taking ethanol after pretreatment with calcium carbimide, a drug commonly used in treatment of alcoholism, were studied by echocardiography. Marked facial flushing and accumulation of acetaldehyde after ethanol were accompanied by circulatory acceleration corresponding in magnitude to at least moderate physical exercise. The heart rate (+/- SD) rose from 58 +/- 6 to 107 +/- 11 beats/min (p less than .001) the cardiac output from 4.1 +/- 0.6 to 9.4 +/- 1.1 L/min (p less than .001), and the ejection fraction from 70 +/- 3 to 89 +/- 2% (p less than .001). The systolic blood pressure rose initially from 121 +/- 6 to 143 +/- 5 mmHg (p less than .001). The diastolic blood pressure declined from 80 +/- 0 to 51 +/- 13 mmHg (p less than .01), and the estimated peripheral resistance to one-third of its preethanol level (p less than .001). These marked cardiovascular changes suggest that the ethanol-calcium carbimide interaction can be hazardous to alcoholics with ischaemic or other forms of myocardial diseases.
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PMID:Possible cardiovascular hazards of the alcohol-calcium carbimide interaction. 715 43

Chlorpropamide alcohol flushing (CPAF) in non-insulin-dependent diabetics (NIDDs) has been reported to be associated with a lower tendency to develop late complications. The flush was thought to be mediated by enkephalins and prostaglandins. Early studies could not correlate CPAF to increased levels of acetaldehyde in blood and the flush was not regarded as an antabuse-like reaction. In this study, the increase of plasma acetaldehyde during the flush in 13 CPAF positive diabetics was significantly (P less than 0.005) higher than in the 13 CPAF negative diabetics during a CPAF challenge test. The increase of plasma acetaldehyde was reduced to the level of CPAF negative diabetics in three CPAF positive diabetics when they were exposed to alcohol without premedication with chlorpropamide and they did not flush. The normal breakdown of ethanol to acetic acid via acetaldehyde appears to be inhibited by chlorpropamide in the flushers. Acetaldehyde measurement is an objective method to study the chlorpropamide alcohol flush and it appears superior to the measurement of skin temperature.
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PMID:Increase of plasma acetaldehyde. An objective indicator of the chlorpropamide alcohol flush. 726 73

Young healthy Japanese men were given 0.48 g ethanol/kg body weight orally. Those responding with a marked increase in heart rate after alcohol also exhibited facial flushing and had higher acetaldehyde levels than those not responding, in spite of similar blood alcohol levels. The activity of aldehyde dehydrogenase in erythrocytes was found to correlate significantly (r=-0.73, p < 0.01) with the increase in heart rate after alcohol drinking. It is suggested that erythrocyte aldehyde dehydrogenase activity affects or reflects blood acetaldehyde levels and physiological response to alcohol, and may prove useful as a marker for alcohol sensitivity in Orientals.
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PMID:Correlation between human erythrocyte aldehyde dehydrogenase activity and sensitivity to alcohol. 741

A sensitive method for determination of human blood acetaldehyde (AcH), which avoids artefactual ethanol-derived Ach formation, was developed. AcH was trapped by collecting blood directly into isotonic semicarbazide, the plasma separated, AcH liberated by perchloric acid and analyzed by gas chromatography. Breath AcH was also trapped in semicarbazide and analyzed similarly. Using an experimentally determined blood:breath partition ratio of 190, calculated pulmonary blood and measured antecubital blood AcH were very similar at various concentrations. Blood AcH was found generally to be very low (< 10 microM) at moderate ethanol levels. Calcium carbimide (0.25 mg/kg) caused moderate flushing reactions and elevated AcH to 25-188 microM. 4-Methylpyrazole (5 mg/kg i.v.) rapidly attenuated AcH levels and symptoms, indicating its potential use in the treatment of disulfiram-ethanol reactions. AcH in the cerebrospinal fluid of 5 highly intoxicated patients was almost absent (0-5 microM). Blood AcH in occasional or chronic alcohol abusers were generally low (< 10 microM), elevated AcH levels being observed only in association with clinical abnormalities. The results indicate that in general, previously reported human blood AcH levels are erroneously high and that breath levels reflect blood levels. Blood AcH may play a lesser role in the actions of ethanol in humans than is often assumed.
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PMID:Low acetaldehyde levels in blood, breath and cerebrospinal fluid of intoxicated humans as assayed by improved methods. 742 34


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