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)

A study was undertaken to examine the relationship between blood acetaldehyde levels and clinical responses in volunteers receiving the anti-alcohol drugs disulfiram and calcium cyanamide. In the first part of this study volunteers received different doses of disulfiram (125 mg and 500 + 250 mg), of calcium cyanamide (25 mg, 50 mg and 100 mg) and of ethanol (0.2 g/kg orally and 0.5 g/kg intravenously). The ensuing interactions ranged from no reaction at all to an intense hypotensive cyanamide-ethanol reaction (CER). A blood acetaldehyde concentration-effect relationship was suggested. In the second part of this study seven subjects received 50 mg of calcium cyanamide 4 hr prior to an intravenous ethanol dose of 0.2 g/kg. The maximum blood level of acetaldehyde ranged from 16 to 241 microM. Aversive interactions started to occur at acetaldehyde levels around 40-60 microM. Changes in flushing reaction and diastolic blood pressure appeared best to reflect changing blood acetaldehyde levels. As a rule, however, the expected cyanamide-ethanol and disulfiram-ethanol reactions are more clearly registered as an increase in acetaldehyde levels than as the ensuing physiological responses.
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PMID:Clinical responses in relation to blood acetaldehyde levels. 159 34

It has been suggested that raised post-ethanol plasma acetaldehyde levels, from inhibition of aldehyde dehydrogenase, underlie the liability to chlorpropamide, alcohol flushing (CPAF). We tested the hypothesis that acetate formation from acetaldehyde, the reaction catalysed by that enzyme, was also likely to be affected by chlorpropamide (CP) medication. In six healthy non-diabetic 'non-flushers', fasting acetate (Ac +/- s.d. mmol/l) was 0.22 +/- 0.12, and increased by 0.47 +/- 0.14 to peak levels by 30 min after intake of 40 ml dry sherry, which increased plasma ethanol (mmol/l) levels to 10.2 +/- 6.0. After 5 days of CP (250 mg daily), fasting Ac (0.17 +/- 0.05) and increase to peak of Ac and ethanol after 40 ml sherry (0.56 +/- 0.12 and 8.9 +/- 7.2 respectively), were not changed (P n.s.). There was no correlation between Ac and ethanol at any time point. When the studies were repeated in five non-insulin-dependent diabetic 'flushers', both on regular CP medication and after 3 days without CP, there was again no significant difference in fasting and post-ethanol Ac levels between the two studies (fasting 0.18 +/- 0.04 v. 0.17 +/- 0.02, and increase to peak 0.62 +/- 0.13 v. 0.72 +/- 0.18, P n.s.). These results indicate that the conversion of ethanol to acetate is unaffected by CP medication, and furthermore that post-ethanol acetate levels do not predict liability to CPAF.
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PMID:The formation of acetate from ethanol with and without prior chlorpropamide intake in diabetic and non-diabetic subjects. 190 25

Ethanol sensitivity is a syndrome of flushing, tachycardia, weakness, fatigue, and other dysphoric symptoms in response to relatively small doses of ethanol. We describe a case of extreme ethanol sensitivity presenting with coma and review the pathophysiology of the syndrome.
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PMID:Ethanol sensitivity. 192 88

The correlation among degrees of alcohol intoxication, facial flushing, blood alcohol concentration (BAC) and blood acetaldehyde level was studied in 117 male alcoholic patients who underwent various tests to assess alcohol influence. Blood samples were collected and alcohol and acetaldehyde levels were determined. BACs ranged from 29 to 577 mg/dl in all patients and from 200 to 299 mg/dl in 48 of them. Fifty-one patients could stand erect (mean BAC [+/- SD] = 189 +/- 80 mg/dl), while 48 showed apparently normal reaction to a walking and turning test (mean BAC = 192 +/- 78 mg/dl). Some of the cases having BACs over 300 mg/dl could still stand and walk while others with BACs under 100 mg/dl already showed psychomotor impairment. Facial flushing was recognized in 75% of the subjects. Acetaldehyde concentrations in 27 patients ranged from 24 to 147 micrograms/dl. Appearance of facial flushing was correlated with relatively high concentrations of blood acetaldehyde. Seven out of 10 healthy volunteers given 1.6 to 2.0 g/kg of alcohol as a control could do nothing but sleep after reaching peak BAC (mean = 232 +/- 21 mg/dl). These findings are taken to indicate a great difference in response to alcohol between alcoholics and healthy men. This study is the first to report the occurrence of facial flushing and raised blood acetaldehyde concentration among Japanese alcoholics.
J Stud Alcohol 1991 Sep
PMID:Degrees of alcohol intoxication in 117 hospitalized cases. 194

The aim of this study was to investigate the relation between Antabus dosage and the disulfiram-alcohol reaction (DAR) after ethanol challenge. Fifty-two healthy volunteers, 29 men and 23 women, aged 20-61 years, were treated with increasing doses of Antabuse (1, 100, 200, 300 mg) for 14 days each. At the end of each 14 days the volunteers were challenged with 0.15 g ethanol/kg body weight. Blood pressure, pulse rate, respiration rate, and symptoms such as flushing, heat sensation, nausea, vomiting, palpitations, breathlessness, and headache were monitored for the next 50 min. The volunteers left the study when they had experienced a valid DAR. A valid DAR, which was principally defined on the basis of the patients' feeling of discomfort, but for safety reasons also on the basis of unacceptable circulatory changes, was reached in 21 out of 52 volunteers after 100 mg Antabuse, in 27 after 200 mg, and in 4 after 300 mg. Most of them left the study after flushing and circulatory changes, but did not feel ill enough to be convinced that they should abstain from drinking. Ten volunteers with weak subjective symptoms, but with a valid DAR, were therefore rechallenged after the next increased dose and experienced a somewhat stronger reaction. We conclude that a daily dose of 200 mg Antabuse brings about a substantial reaction in volunteers in the presence of alcohol. The possible need for a 300 mg dose of Antabuse to prevent a patient from drinking was discussed.
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PMID:Dose-effect relationship of disulfiram in human volunteers. I: Clinical studies. 205 46

A cutaneous test has been applied in examination of the flushing response to ethanol and acetaldehyde in 402 Chinese of Han ethnicity. Using this noninvasive method, five response subtypes have been observed: (A) fast flushing to both ethanol and acetaldehyde; (B) fast flushing only to ethanol but not to acetaldehyde; (C) slow flushing to ethanol only; (D) no response either to ethanol or to acetaldehyde; (E) vasoconstriction to ethanol, or to both ethanol and acetaldehyde. A total of 94% in subtype (A) are reported to be flushers, while only 25% was reported in subtype (D). Other physiological responses, such as tachycardia, dizziness, headache, drowsiness, and nausea are less frequent after alcohol ingestion. The recent history of consumption of alcohol of the subjects in different subtypes was also obtained. Although alcohol-induced flushing is thought to be a deterrent factor to heavy consumption of alcohol, the frequency of drinking of alcoholic beverages was not found to be different between flushers and nonflushers.
Alcohol Clin Exp Res 1990 Dec
PMID:Cutaneous vasomotor sensitivity to ethanol and acetaldehyde: subtypes of alcohol-flushing response among Chinese. 208 31

Members of 183 families (biological parents and one adult offspring) completed questionnaires on their quantity and frequency of alcohol use, what they would consider a "normal" quantity-frequency of alcohol use, "problem" quantity-frequency of use, flushing after alcohol use, and other expected physiological and subjective responses to alcohol. Within individuals, own quantity-frequency of alcohol use was moderately negatively correlated with flushing after one drink or less ("fast flushing"), but more highly positively correlated with judged normal alcohol use and with expected subjective effects. Spouse resemblances were low for quantity-frequency of alcohol use and flushing, but high for alcohol use norms and expected physiological and subjective responses. Parent-offspring resemblances were low to moderate for own alcohol use and flushing, but moderate to high for expected physiological and subjective effects. These results were discussed in terms of the effects of genetically transmitted flushing after alcohol use and culturally transmitted alcohol norms and expectations on alcohol use.
Alcohol Clin Exp Res 1990 Apr
PMID:Familial transmission of alcohol use norms and expectancies and reported alcohol use. 219 Apr 88

Human ethanol consumption has a profound impact on nutritional status, causing major alterations in intermediary metabolism and critical deficiencies of vitamins and trace elements. The major enzyme systems responsible for the principal steps in ethanol metabolism have been characterized and the genes cloned, and significant functional polymorphisms have been identified. An inactive allele of the mitochondrial ALDH is associated with flushing and reduced alcohol intake. This allele may also confer greater sensitivity to some of ethanol's toxic effects. In populations not possessing this variant, twin and adoptive studies have revealed that heritability for alcoholism is greater than 50%. The occurrence of three functional polymorphisms in the ethanol metabolic pathway, including two mutations which are conserved across populations, suggests a role for selection in their maintenance. The two general categories of selective forces to maintain these polymorphisms are food toxins and infectious diseases. Of the infectious agents, amoebi and other anaerobic and microaerophilic organisms of the gut are the most logical candidates.
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PMID:Genetic epidemiology of ethanol metabolic enzymes: a role for selection. 219 94

The types of isozymes of aldehyde dehydrogenase (ALDH) present in human lymphocytes has been investigated using isoelectric focusing of polyacrylamide gels followed by substrate-specific staining. Lymphocytes obtained from most individuals were found to contain both types I and II ALDH. This group of 'typical' individuals reported that they did not develop marked facial flushing or rapid heart rate after drinking alcohol nor did they develop an erythema to cutaneously applied ethanol. Lymphocytes obtained from 'atypical' individuals who do suffer from alcohol-induced flushing and rapid heart rate and who developed erythema to cutaneous ethanol displayed type II, but not type I, ALDH. Lymphocytes thus appear to be an easily accessible and suitable tissue for determining type I ALDH phenotype.
Alcohol Clin Exp Res 1990 Aug
PMID:Isoenzymes of aldehyde dehydrogenase in human lymphocytes. 222 Dec 79

The plasma concentrations of neuropeptides (neurotensin, substance P, motilin, somatostatin, vasoactive intestinal peptide and gastrin-releasing peptide), the urinary excretion of 5-hydroxyindoleacetic acid and serotonin, and the platelet concentration of serotonin were compared in 133 patients who could be assigned to one of four groups. These groups were as follows: carcinoid tumors present; history of carcinoid tumors; miscellaneous tumors present; and non-tumor diseases. The test with the most sensitivity (i.e., patients with carcinoid tumors labeled positive) and the test with the most specificity (i.e., patients without carcinoid tumors labeled negative) for the presence of carcinoid tumors was determined. Urinary 5-hydroxyindoleacetic acid excretion had a sensitivity of 73 percent and a specificity of 100 percent; the plasma concentration of substance P had a sensitivity of 32 percent and a specificity of 85 percent; and the plasma concentration of neurotensin had a sensitivity of 41 percent and a specificity of 60 percent. Even when basal plasma concentrations of substance P and neurotensin were elevated, there was no additional increase of these neuropeptides prior to ethanol-induced facial flushing. Although measurements of plasma neuropeptide levels may be helpful in occasional patients with carcinoid tumors, it is concluded that measurements of serotonin overproduction--such as 5-hydroxyindoleacetic acid excretion--are of more general value.
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PMID:Role of neuropeptides and serotonin in the diagnosis of carcinoid tumors. 243 80


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