Yasuhiko Mizoi

Decreased Serotonin S2 and Increased Dopamine D2 Receptors in Chronic Schizophrenics

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.

Relationship between facial flushing and blood acetaldehyde levels after alcohol intake

Normal subjects were divided into two groups, i.e., those showing, and those not showing, facial flushing after consuming a small amount of alcohol. In the flushing group, increases of pulse rate, facial skin temperature and carotid arterial pressure and blood flow rate, as well as changes of digital plethysmogram and electrocardiogram, were found together with a conspicuous rise in blood acetaldehyde levels after the drinking. However, significant changes of the signs as mentioned above and elevation of blood acetaldehyde did not occur in the non-flushing group. The maximum blood alcohol levels and the rate of alcohol elimination showed not difference between these two groups. Furthermore, urinary excretions of epinephrine and norepinephrine increased in the flushing cases after the drinking.

Alcohol sensitivity related to polymorphism of alcohol-metabolizing enzymes in Japanese

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%.

Determination of β-carbolines in foodstuffs by high-performance liquid chromatography and high-performance liquid chromatography-mass spectrometry

Abstract A high-performance liquid chromatographic method combined with fluorimetric detection is described for the determination of β-carboline(norharman) and 1-methyl-β-carboline (harman). The analysis of foodstuffs for the identification of β-carbolines is facilitated by clean-up of samples using Bond Elut PRS cartridges. Recoveries were excellent. Further, a high-performance liquid chromatographic-mass spectrometric method was also developed for their identification. The concentration of β-carboline among the foodstuffs and alcoholic beverages varied greatly. Also, norharman and harman were observed in uncooked foodstuffs, whereas acetaldehyde was found in most fermented food. The toxicological implication of β-carbolines in foodstuffs is discussed.

The determination of acetaldehyde in human blood by the perchloric acid precipitation method: The characterization and elimination of artefactual acetaldehyde formation

Abstract 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.

Polymorphism of aldehyde dehydrogenase and ethanol elimination

The influence of polymorphism of aldehyde dehydrogenase (ALDH) on ethanol elimination was investigated. Japanese healthy male volunteers were divided into two groups, i.e., a normal ALDH group of 52 subjects with the low Km isozyme of ALDH, and a deficient group of 48 subjects without it. The subjects of the normal group were given 0.4, 0.8, 1.2, 1.6 or 2.0 g/kg of ethanol, while those in the deficient group ingested 0.4, 0.8 or 1.2 g/kg of ethanol. Widmarks factors (beta 60, Co and r) and ethanol elimination rate (ER) were compared between the two groups. In the deficient group, beta 60 and ER were not clearly elevated with the increase of ethanol dose, while those in the normal ALDH group increased depending on the blood ethanol level. Blood acetaldehyde level was elevated with the increase of the ethanol dose in the deficient group, but not in the normal group. In the experiment of the repeated ingestion of ethanol in the deficient group, the second peak of blood acetaldehyde level was lower than that of the first one.

Differences in the intracranial pressure caused by a 'blow' and/or a 'fall'--an experimental study using physical models of the head and neck

In cases of a severe head injury caused by a fall, coup contusions are either absent or very minor, in contrast to presence of extensive contre-coup damage. In cases of a severe blow to head, however, the reverse occurs, with contre-coup lesions a rarity and coup damage extensive. To investigate this further, head injuries caused by a blow or a fall have been studied, using physical human models of the head and neck, both filled with distilled, degassed water and fixed onto a dummy torso. An impact of a constant magnitude was applied to the midoccipital region in blow and fall experiments, and the acceleration of the head and changes in the intracranial pressure were measured, with the resulting data analyzed by a computer. In both experiments, the peak amplitude of the acceleration pulse were almost the same. Similarly, the intracranial pressure curve at the impact site consisted of a positive pulse that hardly differed, nor did the peak amplitude of that pulse vary significantly. In the blow experiment, however, the intracranial pressure curve at the site opposite the impact consisted of a negative pulse, whereas in the fall experiment, the intracranial pressure recorded at the same area was negative but of a longer duration, with an absolute value that was slightly greater. Our results indicate that an impact to the head triggers a different response in the intracranial space, dependent on whether that impact force was caused by a blow or a fall.

Effect of acetaldehyde on urinary salsolinol in healthy man after ethanol intake

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.

Individual difference in urinary excretion of salsolinol in alcoholic patients

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.

Impact-induced intracranial pressure caused by an accelerated motion of the head or by skull deformation; an experimental study using physical models of the head and neck, and ones of the skull

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.