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)

Objective methods to study the chlorpropamide alcohol flush (CPAF) have been inadequate. Determination of blood acetaldehyde has proved to be a promising method, but the analysis is difficult and time-consuming. To measure the facial skin temperature is more handy. The results of these measurements can be presented as delta T (skin temperature increase), %T (per cent of maximum possible temperature rise) or delta MTCI (malar thermal circulation index) after calculations. The baseline skin temperature is accounted for in %T and delta MTCI. Blood acetaldehyde determinations and placebo-alcohol tests can be used to separate the CPAF reaction from alcohol flushing. Single dose CPAF tests including facial skin temperature measurements were performed in 133 type 2 (non-insulin dependent) diabetics. Facial flush was observed in 42.9%. The specificity and sensitivity of all three skin temperature methods were high: 88.2, 85.5, 96.1%, and 89.5, 86.0, 86.0%, respectively. Skin temperature measurement, whether expressed as delta T, %T or delta MTCI, provides a method to study CPAF with high accuracy.
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PMID:Facial skin temperature in chlorpropamide alcohol flush. 399 36

Alcohol-sensitive Japanese subjects with facial flushing and an increase in heart rate during ethanol intoxication exhibited marked individual variation in accumulation of acetaldehyde. This variation correlated well with the intensity of the above mentioned physiological responses. Oral pretreatment with 10 mg/kg 4-methylpyrazole, which inhibited the ethanol elimination rate by 15-25%, strongly suppressed both acetaldehyde accumulation and the associated responses. Under this condition, the sensitivity to acetaldehyde appeared to be reduced, and the correlation between the acetaldehyde level and the physiological responses disappeared. The effectiveness of even a low dose of 4-methylpyrazole suggests its clinical usefulness for alleviation of acute acetaldehyde toxicity in alcohol-hypersensitive Japanese individuals as well as in disulfiram-treated alcoholics.
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PMID:Suppression of acetaldehyde accumulation by 4-methylpyrazole in alcohol-hypersensitive Japanese. 402 Dec 29

New reliable methods for the determination of acetaldehyde in human blood, either from separated plasma or from acid-precipitated whole blood, demonstrate that the blood of healthy Caucasians contains at most only extremely small amounts of acetaldehyde (less than 1 microM) after moderate alcohol intoxication. On the other hand, among about 50% of the Japanese population ethanol ingestion results in elevated blood acetaldehyde levels (10-50 microM) with consequent unpleasant cardiovascular responses such as facial flushing and tachycardia, apparently because of a lack of one of the acetaldehyde-oxidizing aldehyde dehydrogenase isozymes. Elevated acetaldehyde levels may eventually occur also among intoxicated Caucasian alcoholics, primarily as a consequence of abuse-induced loss of hepatic aldehyde dehydrogenase activity, but accentuated by an accelerated ethanol oxidation rate. The elevation is probably reversible, since no acetaldehyde is seen in alcoholics after abstinence and hospital treatment. There is thus little evidence that an elevation of acetaldehyde could serve as a marker for predisposition for alcoholism.
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PMID:Human blood acetaldehyde levels: with improved methods, a clearer picture emerges. 634 52

Treatment for 2 days with disulfiram (3.5 mg/kg once daily) and calcium carbimide (0.7 mg/kg twice daily) in social drinkers produced, as compared to controls, similar blood ethanol values, 2- to 3-fold increases in blood acetaldehyde, respectively, and increased heart rate, pulse pressure, skin temperature, and flushing following 0.15 g/kg of ethanol taken 12 hr after the last drug administration. Peak blood acetaldehyde concentration was greater for calcium carbimide compared to disulfiram (p less than 0.05) and subjects treated with calcium carbimide experienced greater discomfort compared to disulfiram due to palpitations and shortness of breath, and they reported less intention to drink during the reaction. However, neither drug produced sufficient aversion to curtail further drinking totally. With repeated drinks, there was an overall reduction of blood acetaldehyde concentration for calcium carbimide of 85% and for disulfiram of 35%. These data may provide a biochemical basis for the claims of certain alcoholics that they can drink to "burn off" the effects of these drugs.
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PMID:A placebo-controlled double-blind comparative clinical study of the disulfiram- and calcium carbimide-acetaldehyde mediated ethanol reactions in social drinkers. 634 21

Normal Japanese subjects were divided into two groups, i.e., one with both low and high Km isozymes of aldehyde dehydrogenase for acetaldehyde, and the other deficient in the low Km isozyme. After intake of 0.4 g/kg alcohol, the deficient subjects showed high level of blood acetaldehyde, facial flushing and the other dysphoric symptoms, including increase of pulse rate, decrease of diastolic blood pressure, changes of pulse wave in the fingertip, and elevation of the arterial pressure and blood flow rate in common carotid arteries as well as increase of plasma catecholamines level. In contrast, subjects with normal ALDH did not show these changes. From the observation of liver specimens obtained at autopsy, the frequency of deficient phenotype of ALDH in Japanese was presumed to be about 36%.
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PMID:Alcohol sensitivity related to polymorphism of alcohol-metabolizing enzymes in Japanese. 635 56

The metabolism of ethanol and its oxidation product, acetaldehyde, was studied in Japanese volunteers. Subjects who responded by facial flushing and tachycardia were found to accumulate acetaldehyde during ethanol intoxication, in contrast to the near absence of blood acetaldehyde in nonflushing subjects. There were large individual variations in acetaldehyde accumulation observed in the former group, and this accumulation correlated well with the intensity of the physiological responses, but not with rate of ethanol elimination. Oral pretreatment with the alcohol dehydrogenase inhibitor, 4-methylpyrazole, reduced ethanol elimination by 15-25% and strongly suppressed acetaldehyde accumulation. However, here too there was no relation between individual ethanol elimination rate and acetaldehyde accumulation. Furthermore, the change in the blood lactate/pyruvate concentration ratio after ethanol intake was apparently unrelated to the degree of acetaldehyde accumulation. These results, combined with our previous observation of a strong negative correlation between increase in heart rate and activity of cytosolic aldehyde dehydrogenase in erythrocytes, suggest that in flushing Orientals lacking the low-Km aldehyde dehydrogenase isozyme, the alternative cytosolic enzyme is responsible for acetaldehyde oxidation, and its activity probably determines the individual variation of acetaldehyde-mediated physiological responses.
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PMID:Accumulation of acetaldehyde in alcohol-sensitive Japanese: relation to ethanol and acetaldehyde oxidizing capacity. 637 51

While most Caucasians have two main isozymes of liver aldehyde dehydrogenase, in about 50% of Orientals the ALDH I isozyme is missing. This isozyme, which has a faster electrophoretic mobility, is predominantly present in mitochondria and has a relatively low Km for acetaldehyde. The inherent deficiency of ALDH I is responsible for the impaired acetaldehyde oxidation leading to facial flushing and other cardiovascular symptoms of alcohol sensitivity commonly observed in Japanese and Chinese. Antibodies raised against apparently homogeneous liver ALDH I and ALDH II isozymes did not show an immunological similarity between the two isozymes which do not share common subunits. While erythrocyte ALDH II is also immunologically distinct from hepatic ALDH I, it showed an immunological similarity with hepatic ALDH II. On isoelectric focusing in agarose gel followed by immunoelectrophoresis, at least 4 components with an anti-ALDH I antibody were detected in extracts from Caucasian and Oriental livers. In Japanese livers deficient in ALDH I activity, the prominent ALDH component was missing. Apparently, more than one gene is responsible for the synthesis of ALDH isozymes reacting with an antibody against ALDH I. A deletion in one of the genes may be responsible for the loss of ALDH I enzyme activity and altered antigenic properties. However, at this stage, a point mutation in a structural gene coding for ALDH I resulting in a defective protein with altered electrophoretic and enzymatic properties is not ruled out.
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PMID:Basis of aldehyde dehydrogenase deficiency in Orientals: immunochemical studies. 653 15

According to the presence and absence of aldehyde dehydrogenase (ALDH) I isozyme which had low Km for acetaldehyde, subjects were divided into two groups: the former, the usual ALDH group and the latter, the unusual ALDH one. Blood alcohol and acetaldehyde levels, plasma norepinephrine and epinephrine levels, and urinary excretion of norepinephrine, epinephrine, dopamine, vanillylmandelic acid (VMA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined; and the differences in these values and cardiovascular symptoms after alcohol intake between the two groups were investigated. Fifty-six healthy male volunteers were studied after they ingested 0.4 g of alcohol per kg of body weight. There was no difference in blood alcohol level between the two groups. In the unusual ALDH group, facial flushing, increase of pulse rate and decrease in diastolic blood pressure associated with accumulation of blood acetaldehyde were shown. In addition, rises in plasma catecholamine and urinary excretion of catecholamine were also observed. However, in the usual ALDH group, in which blood acetaldehyde level scarcely increased, these changes were not significant. The alteration of catecholamine metabolism, decrease in urinary VMA and increase in urinary MHPG was recognized in both groups.
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PMID:Acetaldehyde-mediated alcohol sensitivity and elevation of plasma catecholamine in man. 662 Jul 25

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


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