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1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) and 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA), both precursors of mutagenic N-nitroso compounds (N-nitrosamines, 1-methyl-2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid and 2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid), were detected in various food-stuffs, urine from healthy human subjects and human milk. A purification procedure, involving a chemically-bonded material followed by HPLC combined with fluorometric detection, was used for the quantitative determination of these compounds, allowing the separation of two diastereoisomers of MTCA. An HPLC and mass spectrometry method was also developed for their identification. Comparing the concentration of MTCA and TCCA in fermented products and raw materials suggested that tetrahydro-beta-carbolines may have been produced through fermentation or by condensation of tryptophan and acetaldehyde formed from ethanol added as a food preservative. This is the first report of excretion of tetrahydro-beta-carbolines in human urine and human milk. A comparison of the concentrations of tetrahydro-beta-carbolines in urine from human infants and human milk indicates that tetrahydro-beta-carbolines may be synthesized endogenously in humans. A possible pathway of tryptophan metabolism in plants and animals is presented.

Rabbit antibodies against albumin-acetaldehyde adduct were used in an enzyme-linked immunosorbent assay to detect acetaldehyde-hemoglobin condensates from the blood of 12 volunteers following ingestion of 1.3 to 2.9 g of ethanol per kg body weight during 8 hr. Blood samples were drawn before drinking and between 2 to 46 hr after starting the drinking session. While there were no significant increases in blood acetaldehyde levels in these samples, acetaldehyde-hemoglobin adducts were significantly increased in the samples drawn after ethanol had been eliminated from the body. Administration of ethanol (0.1 g/kg) to an Oriental flusher resulted in an increase both in blood acetaldehyde and the hemoglobin-acetaldehyde adduct levels. These results suggest that acetaldehyde-hemoglobin condensates are formed in vivo following acute ethanol ingestion. Such condensates may be of value to mark alcohol consumption.

The effect of acetaldehyde on urinary salsolinol (6, 7-dihydroxy-l-methyl-1,2,3,4-tetrahydroisoquinoline) after ethanol intake was investigated. Healthy Japanese male volunteers were divided into two groups, i.e., a normal aldehyde dehydrogenase (ALDH) group of 13 subjects with a low Km isozyme of ALDH and a deficient group of 12 subjects. The subjects were given 0.4 or 0.8 g/kg of ethanol. Blood ethanol and acetaldehyde levels, urinary excretions of salsolinol, norepinephrine, epinephrine and dopamine were determined. A significant elevation of salsolinol in urine was found after intake of 0.8 g/kg of ethanol in the two groups, but the increase in the deficient group was greater than that in the normal group, while 0.4 g/kg of ethanol did not affect the excretion of salsolinol in either group. Blood acetaldehyde was highly correlated with urinary salsolinol (r = 0.88, p less than 0.001) and the correlation coefficient was greater than that between blood ethanol and salsolinol.

Factors influencing ethanol elimination rate and blood acetaldehyde concentration with regard to age, blood ethanol concentration, and degrees of alcoholic liver disorder were studied in alcoholic patients vis-à-vis healthy subjects. Ninety-four male alcoholic patients were divided into five groups according to age and into three groups according to blood ethanol concentration which ranged between 4.21 and 0.29 mg/ml. It was noted that as age increased, blood ethanol concentration decreased. Groups A, B, and C consisted of subjects whose ethanol levels were more than 2.5, between 1.0 and 2.5, and less than 1.0 mg/ml, respectively. Average values of ethanol elimination rate in Groups A, B, and C were 0.26, 0.23, and 0.18 mg/ml/hr, respectively. The rate increased as blood ethanol concentration elevated. The rate in Group B was significantly higher than that in the healthy control subjects who had blood ethanol levels between 1.0 and 2.5 mg/ml. The rate of ethanol elimination was independent of liver disorder judged by liver function test values. Blood acetaldehyde concentrations in the patients were less than 1.48 micrograms/ml, with an average value of 0.58 microgram/ml, and were significantly correlated with blood ethanol levels in both alcoholics and healthy subjects.

An impact incurred by the movable head may bring about a change in intracranial pressure and this change may play an important part in the occurrence of the cerebral contusion. We have carried out the following experiments to determine whether the intracranial pressure change was attributed to an accelerated motion of the head or to a skull deformation. In the blow experiment in which the head was accelerated, a positive peak in the intracranial pressure was recorded immediately after impact at the impact site and a negative one at a site opposite the impact. In the one in which the skull could be deformed, the intracranial pressure curves at both sites contained harmonics. The modal analysis revealed an inbending in the frontal and occipital regions of the skull and an outbending in the parietal and temporal regions immediately after impact, followed by a reverse deformation. Regarding the intracranial pressure change, positive pressures were recorded in the frontal and occipital regions immediately after impact, followed by a negative one. This study demonstrated that the positive and negative peaks were caused by the accelerated motion of the head, and that the curve of the intracranial pressure changes contained harmonics which were caused by the deformation of the skull.

Sixty three male Japanese, aged 20-40 yr were evaluated as to the degree of facial flushing following a controlled dose of ethanol either as Japanese rice wine or ethanol 0.4 g kg body weight. Thirty four subjects responded with overt facial flushing. The acetaldehyde levels in blood and expired air were significantly higher in the flushing group without a change in ethanol elimination rate. Urinary excretion of Vanilmandelic acid (VMA) and 3 methyoxy-4-Hydroxyphenylglycol (MHPG) are reported.

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%.

A 5-year-old boy had his chest compressed by the moving belt of an escalator for about 10 to 15 minutes. The patient suffered seizures and was unconscious for eight months. The clinical and histological findings are reported, and compared with the findings of experiments on fatal chest compression in rabbits.

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.

Serotonin S2 and dopamine D2 receptors in the prefrontal cortex and caudate nucleus of postmortem brains of chronic schizophrenics were studied using 3H-ketanserin and 3H-spiperone, respectively. In the prefrontal cortex of schizophrenics, we found a significant decrease in the maximum number of 3H-ketanserin binding sites (Bmax), with no change in the dissociation constant (Kd). Conversely, both Bmax and Kd of 3H-spiperone binding to the caudate nucleus were significantly increased in the schizophrenic patients. There were no differences in receptor indices between patients who were taking neuroleptics until their death and those who had taken none for 2 months or more prior to death. These findings suggest that alterations in S2 receptors in the prefrontal cortex may reflect the disease process, per se, and that the increase in the number of D2 receptors in the caudate nucleus of schizophrenics is not due solely to neuroleptic medication.

An improved method for treating human blood samples taken for acetaldehyde analysis is presented. The protein precipitation is performed by instant and thorough mixing of the blood sample in a saline solution of perchloric acid. This procedure effectively reduces the artefactual formation of acetaldehyde that occurs during the protein precipitation. The remaining artefactual acetaldehyde, which is mainly formed during the incubation prior to head-space analysis, can be corrected for by a correction curve made using control blood to which ethanol has been added.

Urinary excretion of salsolinol (6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline) in 30 male alcoholic patients during the withdrawal period was determined. They were divided into two groups, i.e., Group A with 14 subjects had a high level of urinary salsolinol (51.9 +/- 40.8 ng/mg creatinine) on admission to a hospital, and Group B with 16 subjects showed a low level of the substance (3.9 +/- 1.9 ng/mg creatinine). Following a sustained drinking bout, urinary salsolinol in Group A declined to a normal level within a few days. We found that the subjects in Group A showed a greater excretion of urinary dopamine and norepinephrine than those in Group B. There were no differences between the two groups in levels of blood ethanol, serum GOT, GPT and gamma-GTP.