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)

Research into the causes of alcoholism is a relatively recent scientific endeavor. One area of study which could lead to better understanding of the disease is the possibility of a genetic predisposition to alcoholism. Recent work has demonstrated that people have varying complements of enzymes to metabolize alcohol. Current knowledge is examined about the influence of various ethanol metabolizing enzymes on alcohol consumption by Asians and members of other ethnic groups. The two principal enzymes involved in ethanol oxidative metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). ADH is responsible for the metabolism of ethanol to acetaldehyde. ALDH catalyzes the conversion of acetaldehyde to acetate. The different isozymes account for the diversity of alcohol metabolism among individuals. An isozyme of ADH (beta 2 beta 2) is found more frequently in Asians than in whites, and an ALDH isozyme (ALDH2), although present in Asians, often is in an inactive form. The presence of an inactive form of ALDH2 is thought to be responsible for an increase in acetaldehyde levels in the body. Acetaldehyde is considered responsible for the facial flushing reaction often observed among Asians who have consumed alcohol. A dysphoric reaction to alcohol, producing uncomfortable sensations, is believed to be a response to deter further consumption. Although the presence of an inactive ALDH2 isozyme may serve as a deterrent to alcohol consumption, its presence does not fully explain the levels of alcohol consumption by those with the inactive isozyme. Other conditions, such as social pressure, and yet undetermined biological factors, may play a significant role in alcohol consumption.
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PMID:Research on alcohol metabolism among Asians and its implications for understanding causes of alcoholism. 251 95

This study examined the skin-flushing response in Asian men, which is a low-risk factor for alcoholism. Asian men who did and did not flush to alcohol consumed 0.5 g/kg ethanol during three sessions with alcohol, and placebo in a fourth session. The results indicated that: (a) Asian men who flushed to alcohol showed pronounced cardiovascular changes that did not exhibit differential tolerance over 3 sessions, (b) there were surprisingly few self-reported mood differences in response to alcohol between those who did and did not flush, and (c) finger-pulse amplitude decreased and self-ratings of "boastful" increased significantly in response to placebo challenge in those men who did not flush. These results raise questions about the psychological mechanisms by which the skin-flushing response inhibits the development and expression of alcoholism.
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PMID:The skin-flushing response: autonomic, self-report, and conditioned responses to repeated administrations of alcohol in Asian men. 259 76

The ethanol patch test, which is considered to be a cutaneous model of flushing, was performed on 311 healthy Japanese (237 adults and 74 children). By comparing the results with aldehyde dehydrogenase (ALDH) phenotype determined by isoelectric focusing from hair roots samples, it was demonstrated that the ethanol patch test is a good indicator of the ALDH phenotype. The usefulness of this test in future studies was discussed.
Alcohol Clin Exp Res 1989 Apr
PMID:Ethanol patch test--a simple and sensitive method for identifying ALDH phenotype. 265 61

We have identified PAF in the blister fluid from a patient with bullous mastocytosis, a rare form of mast-cell disease. We have found a novel endogenous inhibitor of platelet aggregation which obscured the presence of the PAF in unprocessed blister fluid and in ethanol or lipid extracts. The PAF was characterized by the demonstration of chromatographic, mass spectral and biological properties identical to those of authentic PAF. Thus this is the first demonstration of PAF in biological fluid from a patient with mastocytosis. High levels of immunoreactive prostaglandin D2 (PGD2) and histamine were also present in the blister fluid. The interaction between PAF and the inhibitor of platelet aggregation in patients with systemic mastocytosis may provide an explanation for some of the manifestations of the disease, in particular the episodic hypotension, cutaneous flushing and pallor.
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PMID:Occurrence of platelet-activating factor (PAF) and an endogenous inhibitor of platelet aggregation in diffuse cutaneous mastocytosis. 280 9

The so-called Oriental flushing reaction associated with ingestion of small amounts of alcohol was antagonized by combined antihistamine administration. In stage one of the study, the flushing reaction to low doses of alcohol was produced in Orientals. Most subjects experienced a cutaneous flush, increase in skin temperature, decrease in blood pressure, increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness and nausea. One half of the group of subjects was then given diphenhydramine, 50 mg (H1 receptor antagonist) and cimetidine, 300 mg (H2 receptor antagonist) and the second half received placebo tablets before the administration of alcohol. The clearest difference between the antihistamine group and placebo group was in the skin flushing reaction. The antihistamine group showed a statistically significant reduction in the skin flush. The antihistamines also neutralized the systolic hypotension induced by the administration of alcohol.
Alcohol Alcohol Suppl 1987
PMID:Combined antihistamine antagonism of the flushing reaction to alcohol. 289 99

The effects of chronic consumption of some beverages (plum-brandy 24% and cognac 20%) upon preimplantation development in rats were studied. The control of possible effects was performed on day 5 by usual flushing, examination and photographying of oviductal and uterine embryos. In order to evaluate the effect of the beverage applied, the following criteria were used: mean litter size, migration of the embryos from the oviduct to the uterus, the developmental stage attained by the pre-implantation embryos and the appearance of pathological embryos. The main results were the following: both beverages applied influenced the preimplantation development; with respect to the developmental rate and to the induction of pathological changes, the effect of both beverages was similar (retardation and an increased, number of pathological morulae and blastocysts); a different action could be detected as to the mean litter size and to the migration of preimplantation embryos: plum-brandy reduced more substantially the mean litter size, whereas cognac had a more marked retarding effect upon the migration of embryos from the oviduct to the uterus: all the changes detected show a more or less marked "litter-effect". The present data were compared with the corresponding effects of chronic ethanol administration observed previously in our laboratory. No obvious potentiating effect of beverage congeners could be established. The findings are discussed in connection with other experimental models of alcohol embryo and fetopathy.
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PMID:The effect of ethanol upon early development in mice and rats. VIII. The effect of chronic consumption of some beverages upon preimplantation development in rats. 293 20

Objective measurements of temperature and blood flow changes by telethermometry and laser Doppler velocimetry (LDV), respectively, were performed continuously in normal subjects after they ingested 0.4 g/kg of ethanol in a volume of 300 mL. Cutaneous temperatures were interpreted by the change in malar thermal circulation index (delta MTCI) method. Both the delta MTCI method and LDV output correlated significantly with the presence of flushing. The delta MTCI method also correlated significantly with LDV output, indicating that the intensity of the flushing reaction can be assessed by both methods. The sensitivity, specificity, and predictive value of a positive result were greater with the LDV method. The time to maximum delta MTCI correlated quite closely with the time to maximum LDV output. The results indicate that both LDV and delta MTCI methods are valid, noninvasive assays for flushing reactions.
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PMID:Quantitative assessment of alcohol-provoked flushing. 293 88

An ethnic predisposition to ethanol-provoked flushing among diverse Mongoloid populations may be the consequence of a delayed oxidation and accumulation of acetaldehyde. Orientals who flush after oral alcohol are more likely to have cutaneous erythema after topical ethanol or propanol, and the cutaneous vascular reaction to primary alcohols is actually provoked by the corresponding aldehyde. The cutaneous reaction to primary alcohols can be totally blocked by pretreatment with 4-methylpyrazole, a potent inhibitor of alcohol dehydrogenase.
Alcohol Clin Exp Res 1985 Dec
PMID:Cutaneous vascular sensitivity to lower aliphatic alcohols and aldehydes in Orientals. 293 66

The existence of racial differences in alcohol sensitivity between Oriental and Caucasian populations has been well documented. The primary manifestation is a highly visible facial flushing (47-85% in Orientals vs 3-29% in Caucasians) accompanied by other objective and subjective symptoms of discomfort. Even among different Oriental groups, subtle differences in the flushing response and alcohol consumption can exist. North and South American Indian populations differ in phenotypes for alcohol dehydrogenase and aldehyde dehydrogenase, but systematic studies comparing degree of flushing, alcohol elimination rates and blood acetaldehyde levels in these populations are lacking. Although flushing does not automatically 'immunize' an individual against alcohol use, those susceptible tend to consume less alcohol, at least in Orientals. However, the flushing phenomenon cannot be the sole explanation for differences in incidences of alcoholism among different racial groups. Socio-cultural, environmental and genetic factors also have to be considered. An increased incidence of flushing has been found to associate with a familial risk of development of future alcoholism in a Caucasian population. It remains to be determined whether the same is true in Orientals. Most biochemical investigations of the flushing phenomenon have focused on aspects of alcohol metabolism. Based on recent findings, a convincing mechanism is the higher accumulation of acetaldehyde in flushing subjects because they have an unusual, less-active liver aldehyde dehydrogenase isozyme (ALDHI). The possibility that an 'atypical' alcohol dehydrogenase, which is present in 85-90% of Oriental subjects, can contribute to increased blood acetaldehyde levels in flushing subjects cannot be ruled out. Based on results of a small number of pedigree studies which demonstrated familial resemblances in flushing, a pharmacogenetic defect in ALDHI has been proposed to be responsible for flushing. Other possible biochemical mechanisms (e.g. prostaglandins) and genetic defects need to be investigated.
Alcohol Alcohol 1986
PMID:Racial differences in alcohol sensitivity. 293 17

Ascorbate reversibly inhibits catalase, and this inhibition is enhanced and rendered irreversible by the prior addition of copper(II)-bishistidine. In the absence of copper, the inhibition was prevented and reversed by ethanol, but not by superoxide dismutase, benzoate, mannitol, thiourea, desferrioxamine, or DETAPAC. In the presence of the copper complex mannitol, benzoate, and superoxide dismutase still had no effect, but thiourea, desferrioxamine, DETAPAC, or additional histidine decreased the extent of inactivation to that seen in the absence of copper. In the presence of copper, ethanol protected at [ascorbate] less than 1 mM, but was ineffective at [ascorbate] greater than 2 mM, even in the absence of oxygen. Although in the absence of copper, complete removal of oxygen provided full protection against inactivation by ascorbate, this protection was not seen if the catalase was briefly preincubated with H2O2 prior to flushing with nitrogen, or if copper was present. In fact, if copper was present, inactivation was enhanced by the removal of oxygen. Increasing the concentration of oxygen from ambient to 100% slowed the inactivation, whether or not copper was present. It is concluded that the initial reversible inactivation involves reaction with H2O2 to form compound I, followed by one electron reduction of compound I to compound II. In the presence of added copper, the initial (reversible) inactivation allows H2O2 to accumulate sufficiently to permit irreversible inactivation. Since in the presence of copper oxygen is not required, and neither the reversible nor the irreversible inactivation was prevented by conventional scavengers of active forms of oxygen, the inactivation is likely mediated by semidehydroascorbate, and/or it may involve site-specific generation of the damaging intermediates.
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PMID:Mechanism of the inhibition of catalase by ascorbate. Roles of active oxygen species, copper and semidehydroascorbate. 300 60


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