Evaluation of acetaldehyde-modified hemoglobin and other markers of chronic heavy alcohol use: effects of gender and hemoglobin concentration.

The present study examined whether measurement of hemoglobin-acetaldehyde (HbA1-AcH) using an improved methodology may be useful as a biological marker of alcohol abuse. Red blood cell hemolysates of 182 patients consecutively admitted to the drug and alcohol treatment unit of our institution were analyzed for HbA1-AcH concentration using cation exchange HPLC. Mean HbA1-AcH of those who claimed to drink > or = 6 drinks/day [mean = 0.055 (% total hemoglobin), SD = 0.051] was significantly higher than the mean of those who drank < 6 drinks/day (mean = 0.026, SD = 0.0174). The greatest sum of sensitivity (67%) and specificity (77%) came with a cut-score of 0.030 area% of total hemoglobin. A cut-score of 0.080 produced a 100% specificity, but lowered the sensitivity to 20%. The Pearson product moment correlation (r) between HbA1-AcH and reported drinks per day was r = 0.30 (p < 0.001). There was no significant difference in the association of HbA1-AcH and reported drinking between males and females, and the small difference observed was shown to be entirely associated with differences in hemoglobin levels between the sexes. Cocaine use did not significantly alter the correlation between reported drinking and HbA1-AcH levels. Hemoglobin levels were shown to have a significant correlation with HbA1-AcH independent of drinking. HbA1-AcH was shown to have a better sensitivity and specificity than gamma-glutamyltransferase, ALT, AST, or mean corpuscular volume in this population. The results suggest that HbA1-AcH may be a useful marker to help detect alcohol abuse, especially in populations where other markers have been shown to fail.

Improved separation of acetaldehyde-induced hemoglobin.

A fast-eluting minor variant of hemoglobin A, designated as HbA1-AcH, appears elevated after the incubation of red blood cell hemolysates with acetaldehyde (AcH) and has been proposed as a diagnostic marker for alcoholism or as an indicator for heavy drinking. We have developed an improved HPLC separation of this peak and others elevated by AcH using a polyaspartic acid column (PolyCAT A, PolyLC, Inc.) and a nonlinear buffer gradient with pH changes from 6.6 to 6.8. Saline-washed red blood cells were treated with sodium acetate buffer (pH 5.5) to remove unstable Schiff bases, and then hemolyzed by addition of an equal volume of H2O and 0.4 volumes of CCI4. HbA1-AcH and several others, including two peaks in the HbA1a+b cluster, Hb Pre-A1c, and HbA1d3 were significantly increased by AcH incubation, and the changes were only partially reversible with time. Improved resolution of these peaks allows more accurate quantitation of AcH adducts of hemoglobin.

Aspirin attenuation of alcohol-induced flushing and intoxication in Oriental and Occidental subjects.

Aspirin (ASA) was tested in a group of 8 Oriental and 3 Occidental subjects who were shown in a previous study to respond to small doses of ethanol (0.06-0.25 g/kg) with facial flushing. They were compared to a similar group of 11 non-flushing Occidental subjects following a larger ethanol dose (0.37 g/kg) to determine if similar effects could be produced in less sensitive individuals. Control tests of blood ethanol and acetaldehyde (AcH) levels (calculated from breath), facial and neck skin temperatures, body sway (Romberg test), blood pressure, heart rate and 10 Subjective High Assessment Scales (SHAS-Judd, 1977) were conducted before and at 15, 30, 60 and 90 minutes after drinking ethanol as vodka in orange juice. The tests were repeated one week later one hour after receiving 0.64 gm of ASA orally. ASA produced slight changes in the early absorption of ethanol and small decreases in AcH levels in the flushing and non-flushing groups. Facial flushing was markedly reduced in the flushing group, but was slightly increased in the non-flushing Occidentals. Body sway was reduced by ASA in both groups. An alcohol-induced increase in heart rate in the flushing group was reduced with no change in blood pressure. SHAS subjective parameters were widely variable, but indicated that ASA produced reduced sleepiness and earlier relaxation in the flushing group. It is concluded that ASA can block alcohol-induced facial flushing in sensitive subjects and also reduces body sway in the Romberg test and alters some subjective feelings of alcohol intoxication.

Acute low-level formaldehyde behavioural and neurochemical toxicity in the rat.

The purpose of the present study was to determine the effects of low-level formaldehyde exposure upon behavior and neurochemistry in the male rat. Rats were exposed to either air or formaldehyde vapor (5, 10 or 20 parts per million) for 3 hours on 2 consecutive days during which behavioral observations were made. Following the second exposure session the rats were sacrificed and their brains analyzed for norepinephrine, dopamine, 5-hydroxytryptamine and their major metabolites. Formaldehyde exposure resulted in decreased motor activity and neurochemical changes in dopamine and 5-hydroxytryptamine neurons.

Marihuana vs. alcohol: a pharmacologic comparison.

A review of the pharmacology, behavior, toxicity and therapeutic actions of alcohol and marihuana shows many similarities between the two drugs and few striking differences. Both drugs have fundamental non-specific actions on the neural membrane in common with the sedative-hypnotic-anesthetic group of drugs. They differ mainly in the quantitative aspects of their action owing to variation in 1) the ratio of stimulant to depressant effects, 2) their distribution in the body because of the greater lipid solubility of delta-9-tetrahydrocannabinol (delta-9THC), 3) the route of intake and 4) in their metabolic transformation. Despite marked contrasts in potency, toxicity and therapeutic potential as a result of these differences it is proposed that the proper pharmacologic classification of both drugs is in the sedative group based on their activity at non-toxic levels rather than regarding marihuana as a primary hallucinogen as presently done in many texts.

Metabolite of (-)-trans-delta 8-tetrahydrocannabinol: identification and synthesis.

The major metabolite of (-)-trans-Delta(8)-tetrahydrocannabinol observed in vivo and formed by hepatic microsomes in vitro is 11-hydroxy-trans-Delta(8)-tetrahydrocannabinol. The metabolite was identified spectroscopically and was synthesized from trans-Delta(8)-tetrahydrocannabinol. In tests with rats, the metabolite produced behavioral effects similar to those imparted by Delta(8)- and Delta(9)-tetrahydrocannabinol.