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)

Human volunteers were given a small dose of ethanol (0.25 g/kg body weight) after pretreatment with either calcium carbimide (50 mg) or a placebo according to a crossover design. Calcium carbimide, an inhibitor of aldehyde dehydrogenase, caused intense facial flushing and a pronounced rise in the concentration of acetaldehyde in breath. At 15-min intervals throughout the experiment, breath-ethanol concentrations were determined both by gas chromatography (GC) (specific method) and by infrared (IR) spectrometry with an Intoxilyzer model 4011 breath-alcohol analyzer. The results with these two independent methods of analysis were compared in experiments with and without calcium carbimide pretreatment. The regression equations relating breath-ethanol determinations by GC and IR methods in the two test situations were not significantly different. The elevated breath concentrations of acetaldehyde associated with a drug-alcohol flush reaction do not invalidate the use of infrared breath-alcohol devices for evidential purposes.
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PMID:Drug-alcohol flush reaction and breath acetaldehyde concentration: no interference with an infrared breath alcohol analyzer. 372 77

It is known that aldehyde dehydrogenase (ALDH) responsible for metabolism of acetaldehyde deriving from ethanol has two distinct forms of isozymes: ALDH-I (low Km ALDH) and ALDH-II (high Km ALDH), and that many Orientals lack ALDH-I isozyme genetically. In the present study, the role of ALDH isozyme variance in the alcohol sensitivity, drinking habits formation and the development of alcoholism was investigated in Japan, Taiwan and the Phillipines. Isozyme analysis using isoelectric focusing of hair roots specimens from normal volunteers or schizophrenics revealed that about 42% of Japanese, 35% of Taiwanese and 12% of Phillipines were ALDH-I deficient. Questionnaire study of Japanese volunteers indicated that ALDH-I deficient individuals showed flushing, palpitation and other uncomfortable somatic signs, due to reduced metabolism of acetaldehyde, much more frequently than ALDH-I positive ones. Consequently, it occurred that only 19% (8/42) of ALDH-I deficient persons, in contrast to 49% (29/59) of ALDH-I positive ones, were drinking habitually. Patients with alcoholism showed much smaller percentages of ALDH-I deficiency: 4% (5/113) in Japan and 10% (3/29) in Taiwan, than those of control subjects. Summarizing these data, a hypothesis can be presented that genetically derived difference of ALDH activities is one of the determining factors in the sensitivity to alcohol, formation of drinking habits, and finally in the development of alcoholism, at least among Oriental peoples.
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PMID:The role of aldehyde dehydrogenase isozyme variance in alcohol sensitivity, drinking habits formation and the development of alcoholism in Japan, Taiwan and the Philippines. 374 13

In the course of celiac plexus alcohol block, facial flushing, palpitations, and hypotension are occasionally incurred in some patients. We hypothesized that the phenomenon represents acetaldehyde syndrome, not response to increased blood levels of ethanol as might be supposed. In order to prove our hypothesis, we selected five patients scheduled to undergo celiac plexus alcohol block, and, with their consent, we measured blood concentration of ethanol and acetaldehyde before and for 6 hr after the block. We also determined the phenotypes of aldehyde dehydrogenase (ALDH) in their hair roots. We found that "flushers" are found exclusively among subjects without ALDH I, and that their blood levels of acetaldehyde were significantly higher than those of "non-flushers" within 10 min after the block. The flushers also gave histories of facial flushing after ingestion of small amounts of ethanol. On the basis of such histories one can anticipate whether acetaldehyde syndrome is likely or unlikely to accompany the block.
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PMID:Acetaldehyde syndrome after celiac plexus alcohol block. 377 61

A rise in blood acetaldehyde concentrations following alcohol ingestion was significantly inhibited when healthy nonflushing subjects were administered a clinical dose of pantethine orally. However, similar findings were not observed in flushing (alcohol-sensitive) subjects lacking hepatic low Km aldehyde dehydrogenase (ALDH). The blood ethanol concentrations were not altered by this treatment in either flushing or nonflushing subjects. Acetaldehyde (45 microM) added in vitro to whole blood and plasma obtained 1 hr after pantethine administration disappeared as the incubation continued similarly as with blood and plasma obtained prior to pantethine treatment. Pantethine-related metabolites, such as taurine, pantetheine, coenzyme A, and pantothenate, activated ALDH in vitro. Hepatic acetaldehyde levels following ethanol loading of rats treated with pantethine were much lower than in untreated rats. The pantethine action observed only in nonflushing subjects might be due to an accelerated oxidation of acetaldehyde by the activation of low Km ALDH by pantethine-related metabolites formed in the liver.
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PMID:Lowering of blood acetaldehyde but not ethanol concentrations by pantethine following alcohol ingestion: different effects in flushing and nonflushing subjects. 389 99

A sensitive high performance liquid chromatography method has been used to measure aldehyde dehydrogenase (ALDH) activity in hair roots from Caucasian and Japanese subjects. Kinetic studies confirmed previous isoelectric focusing results that hair roots from Caucasians have two forms of ALDH, one low Km form and another high Km form, while hair roots from Japanese individuals who show a flushing reaction after ethanol intake lack, or have low activity of, the low Km form. By taking the ratio of the activities measured at a low (3 microM) and a high (75 microM) concentration of the substrate (3,4-dihydroxyphenylacetaldehyde), a suitable index for ALDH deficiency was obtained. The ratio varied between 1.6 and 3.5 for Caucasians and between 7 and 23 for Japanese flushers, and it was 2.5 for a Japanese nonflusher. The current method allows a more quantitative and qualitative assessment of the ALDH isozyme pattern in hair roots than that obtained with the isoelectric focusing technique.
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PMID:Application of a high performance liquid chromatography method for screening of aldehyde dehydrogenase isozyme deficiency in hair roots from different ethnic groups. 390 4

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

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


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