Satoshi Fujiwara

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.

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.

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.

Identification of four metabolites of 3-(phenylamino)alanine,a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in rats

Abstract3-(Phenylamino)alanine (PAA), a contaminant found in l-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in order to determine levels of PAA. The level of PAA in blood was 4.22 μg/ml at 5 h and urinary excretion was 21.7 μg for 5 h and 84.6 μg between 5 and 24 h. The amount of PAA in the contents of the large intestine at 5 h was 0.76 μg, indicating poor transfer of PAA to the large intestine. However, the highest concentration of PAA was 12.3 μg/g in the brain, indicating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabolites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest that the degradation pathway of PAA is similar to that of phenylalanine.

Study on the Mechanism of Traumatic Brain Injury

Skull fracture, intracranial hemorrhage, or cerebral injury can be caused in humans due to a strong impact to the head. The following 2 types of cerebral injuries are often observed: one type is cerebral contusion which is a local brain damage to the brain, and the other is diffuse axonal injury (DAI) which is a diffuse brain damage to the brain. In various head injuries caused by external impact, cerebral contusion and DAI mainly result in direct failure of the cerebral parenchyma.