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Biomedical subjects

O Inoue

Publications and source records attributed to O Inoue.

At least 145 records · Page 8Linked to original sources

Biliary excretion of metabolites of baicalin and baicalein in rats.

Biliary excretion of metabolites of baicalin, present in Scutellariae Radix, was investigated using rats. The bile of rats administered baicalin orally was shown to contain five major metabolites, which were identified as baicalein 6-O-beta-glucopyranuronoside (M1), 6-O-methyl-baicalein 7-O-beta-glucopyranuronoside (oroxylin A 7-O-beta-glucuronide (M2], baicalein 7-O-beta-glucopyranuronoside (M3), 6-O-beta-glucopyranuronosyl- baicalein 7-O-sulfate (M4), and baicalein 6,7-di-O-beta-glucopyranuronoside (M5) on the basis of chemical and spectroscopic evidence. The bile of rats treated with baicalein also contained the above metabolites. Slower biliary excretion of the metabolites after baicalin administration suggested that it was absorbed as baicalein after hydrolysis in the gastrointestinal tract. The total cumulative amounts of the five metabolites excreted in the bile during 30 h after oral administration of baicalin and that of baicalein were approximately 54% and 40% of the doses, respectively. In addition the bilary metabolites of both drugs were shown to be mainly composed of M5 and M4, which have high polarity and large molecular weight.

Animals↗

Relationship between vapor exposure and urinary metabolite excretion among workers exposed to trichloroethylene.

The exposure-excretion relationship was investigated in 140 trichloroethylene (TRI)-exposed workers and 114 nonexposed controls. The time-weighted average intensity of exposure to TRI during the shift as measured by the diffusive sampling method was compared with metabolite levels in the urine collected at the end of the shift in the second half of a working week, when the urinary metabolite levels are expected to reach a maximum. The TRI levels in breathing zone air of the exposed workers were mostly below 50 ppm. The urinary metabolite levels (i.e., total trichloro-compounds, trichloroethanol, and trichloroacetic acid) increased as a linear function of the TRI exposure. The relationship between the two exposure indicators was statistically significant in men, women, and both combined. The cross-sectional balance study at the end of the shift revealed that about 4% of TRI absorbed will be excreted at the end of the shift, in agreement with the long biological half-life of this chlorinated hydrocarbon solvent. A possible ethnic difference in the metabolism of TRI is discussed.

China↗

Dose-excretion relationship in tetrachloroethylene-exposed workers and the effect of tetrachloroethylene co-exposure on trichloroethylene metabolism.

Personal monitoring of 8-hour time-weighted average intensity of exposure with diffuse samplers and analysis of shift-end urine for total trichloro-compounds (TTC) and other metabolites were conducted in two groups of workers in China, one (121 subjects) exposed to tetrachloroethylene (TETRA) alone, and the other (38 subjects) exposed to a mixture of TETRA and trichloroethylene (TRI). Urinalysis was also performed on samples from 103 non-exposed controls. A linear exposure-excretion relationship could be observed in both groups of workers. Comparison of these results with those of Japanese TETRA-workers suggested the presence of ethnic difference in TETRA metabolism. Urinary metabolite levels were markedly lower in the mixed (TETRA + TRI) exposure group as compared to previous findings in a group exposed to TRI alone. The observation indicates that metabolism of TRI is suppressed by the co-exposure to TETRA in humans.

Air Pollutants, Occupational↗

Detection of benzodiazepine receptor occupancy in the human brain by positron emission tomography.

Benzodiazepine receptor occupancy in the brain following oral administration of clonazepam (CZP) with a dose of 30 micrograms/kg in six healthy young men and a further dose of 50 micrograms/kg in one of the subjects was estimated by carbon-11 labeled Ro15-1788 and positron emission tomography (PET). The effects of CZP on the latency of auditory event-related potentials (P300) were also studied. Overall brain 11C uptake was depressed and the % inhibition of 11C uptake in the gray matter of the brain at 30 min after [11C]Ro15-1788 injection was 15.3-23.5% (mean, n = 6) following 30 micrograms/kg CZP when compared with that in the control experiment without any previous treatment. The 11C uptake in the cerebral cortex in the subject who received both doses decreased in a dose-related manner after 30 micrograms/kg and 50 micrograms/kg CZP. The P300 latency was prolonged significantly by 30 micrograms/kg CZP [31.6 +/- 16.3 ms (mean +/- SD, n = 6), P less than 0.05]. The P300 latency in the same subject was prolonged in a dose-related manner by 30 micrograms/kg and 50 micrograms/kg CZP. The technique using [11C]Ro15-1788 and PET permits comparison of the pharmacological effects with the percentage of receptor sites which benzodiazepines occupy in the human brain. P300 also seems to be useful to investigate the pharmacological effects of benzodiazepines.

Adult↗

Synthesis and evaluation of 11C-PK 11195 for in vivo study of peripheral-type benzodiazepine receptors using positron emission tomography.

The biodistribution of 3H-PK 11195, an antagonist of the peripheral-type benzodiazepine receptors, was studied in mice. High accumulations of radioactivity in the heart, lung, spleen, kidney and adrenal were observed after intravenous injection of tracer amounts of 3H-PK 11195 into the mice. The radioactivity in the heart, lung, spleen, kidney and adrenal was significantly decreased by the coadministration of carrier PK 11195, which indicated that PK 11195 specifically binds to the receptors. No radioactive metabolites were observed in the heart, lung and brain 20 min after intravenous administration of 3H-PK 11195. The accumulation of 3H-PK 11195 in the lung was not affected by pretreatment with either alpha-methyl benzylamine or imipramine, suggesting that 3H-PK 11195 specifically binds to the receptors. The ratios of radioactivity of the kidney, adrenal and spleen to blood increased as a function of time, whereas that of the lung and heart rapidly reached to a steady state. 11C-PK 11195 was synthesized by the N-methylation of desmethyl precursor yielding more than 100 mCi with high specific activity (more than 1.4 Ci/mumol). The labeling and purification procedure was completed within 23 min after the end of bombardment (EOB). The 11C-PK 11195 solution for injection seems to have a high potential for the in vivo study of the peripheral-type benzodiazepine receptors in the living human by means of positron emission tomography (PET).

Animals↗

Blood cadmium levels in the populations of 3 Chinese cities.

Blood samples were collected from male and female factory workers aged greater than or equal to 16 years (with no occupational exposure to metals including cadmium) in the 3 cities of Hefei (323 subjects), Shenyang (78 subjects), and Jinxi (137 subjects) in China from 1985 to 1987. The samples were analyzed for cadmium in a single laboratory by automated flameless atomic absorption spectrophotometry under strict quality control. The effect of smoking was evident in Hefei, Shenyang and Jinxi, while the effect of aging was not apparent. There were no sex or regional differences in blood cadmium levels in non-smokers in the 3 cities (e.g., 1.2, 1.3 and 1.4 micrograms/l as geometric means in non-smoking women in Hefei, Shenyang and Jinxi, respectively). There was general agreement in blood cadmium levels between the present results and the values reported in the literature, although the latter values were generally based on small study populations.

Adult↗

Urinary t,t-muconic acid as an indicator of exposure to benzene.

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.

Air Pollutants, Occupational↗

Excretion of 1,2,4-benzenetriol in the urine of workers exposed to benzene.

Urine samples were collected from 152 workers (64 men, 88 women) who had been exposed to benzene, 53 workers (men only) exposed to a mixture of benzene and toluene, and 213 non-exposed controls (113 men, 100 women). The samples were analysed for 1,2,4-benzentriol (a minor metabolite of benzene) by high performance liquid chromatography. The time weighted average solvent exposure of each worker was monitored by diffusive sampling technique. The urinary concentration of 1,2,4-benzentriol related linearly to the intensity of exposure to benzene both in men and women among workers exposed to benzene, and was suppressed by toluene co-exposure among male workers exposed to a mixture of benzene and toluene. A cross sectional balance study in men at the end of the shift of a workday showed that only 0.47% of benzene absorbed will be excreted into urine as 1,2,4-benzenetriol, in close agreement with previous results in rabbits fed benzene. The concentration of 1,2,4-benzenetriol in urine was more closely related to the concentration of quinol than that of catechol. The fact that phenol and quinol, but not catechol, are precursors of 1,2,4-benzentriol in urine was further confirmed by the intraperitoneal injection of the three phenolic compounds to rats followed by urine analysis for 1,2,4-benzenetriol.

Animals↗

Hepatitis B virus infection among women in a shoe factory in Korea.

One hundred and sixty five Korean women in a shoe factory in Masan, Korea were evaluated on hepatitis B virus infection by solid-phase radioimmunoassay in 1986. The participants were women of child-bearing ages, mostly in 20's and 30's. About two thirds (105/165) of the subjects had serological evidence of past or present hepatitis B virus infection, and 17% (28/165) were HBsAg-positive. In view of possible risk of vertical transmission of hepatitis B virus, further epidemiological study was considered necessary to establish preventive measures.

Adolescent↗

[Comparative effects of traditional Chinese medicines (dai-saiko-to, hatimi-zio-gan and byakko-ka-ninzin-to) on experimental diabetes and hyperlipidemia].

In order to clarify the anti-hyperglycemic and anti-hyperlipidemic actions of traditional Chinese medicines, experiments were carried out with experimentally diabetic rats induced by cyproheptadine treatment. The following results were obtained: 1) Dai-saiko-to decreased the blood glucose level at 30, 60 and 120 min after glucose loading in the tolerance test; and the drug tended to increase serum insulin level and increased the ratio (glucose/insulin) at 120 min after the glucose loading. A significant decrease in serum total cholesterol was observed in the high fat diet-treated rats. 2) Hatimi-zio-gan also decreased the blood glucose level at 30 and 120 min after glucose loading. The drug did not lower the serum insulin, but rather increased the glucagon level at 120 min after the loading. The serum lipid level was not reduced by the drug. 3) Byakko-ka-ninzin-to also increased serum glucagon at 120 min, but no change of glucose and lipid in the sera under the above experimental conditions was observed. Such experimental results suggest that Dai-saiko-to might exert an effect that can improve the pathological conditions of diabetes mellitus.

Animals↗

Hemodynamic evaluation and morphological changes of right ventricular out-flow tract and pulmonary valve after balloon pulmonary valvuloplasty.

Balloon pulmonary valvuloplasty (BPV) was attempted in 38 cases of congenital pulmonary valve stenosis. It was effective and was done without complication in 36 cases, however it was not effective in two cases of pulmonary valve dysplasia. The balloon used was 20-50% larger in diameter than the pulmonary valve annulus. In the seven cases in which the transvalvular pressure gradient was above 100 mmHg on cardiac catheterization, right ventriculography demonstrated that the functional obstruction of the right ventricular outflow tract increased immediately after BPV, however it subsequently improved at one year after the procedure. At between one and three months after BPV, two-dimensional echocardiography demonstrated that the morphological obstruction to the right ventricular outflow tract had diminished. In two cases, localized right ventricular septal hypertrophy with severe pulmonary valve stenosis was observed by two-dimensional echocardiography and right ventriculography, and persisted at one year. In all cases, two-dimensional echocardiography and angiography demonstrated doming pulmonary valves with valve stenosis, which was diminished by BPV. The pulmonary valve morphology was observed by two-dimensional echocardiography in three cases following BPV. In one case, partial relief of pulmonary valve obstruction was seen to be due to commissural splitting and in the other two, to tearing of cusp tissue. Inspection of the pulmonary valve at operation was made in one case who underwent elective surgery for repair of an atrial septal defect which was associated with pulmonary valve stenosis. It demonstrated partial relief of pulmonary valve stenosis by tearing of cusp tissue. In conclusion, BPV is as effective a treatment for congenital pulmonary valve stenosis as open valvulotomy. In our follow-up study, it has shown no apparent complications. The transient obstruction in the right ventricular outflow tract immediately after BPV improved within one month and improved further after three months and one year. However, in the more long-standing cases the localized right ventricular septal hypertrophy persisted and these cases will require, a long term follow-up.

Blood Pressure↗

[Age-related decrease of 11C-N-methylspiperone in vivo binding to human striatum detected by PET].

The effect of aging on 11C-N-methylspiperone binding to living human striatum was demonstrated using positron emission tomography. The 11 normal volunteers (22 to 72 years old) participated in this study. The uptake of 11C-N-methylspiperone in the brain following intravenous injection was highest in the striatum in individual subject. And the uptake in the striatum only gradually increased until the end of the study. The uptake of 11C-N-methylspiperone in cerebellum peaked within 10 minutes following injection and then rapidly dropped. The association rate constant "k3" was calculated from the slope of the radioactivity-ratio of striatum to cerebellum versus the equivalent time. The equivalent time was calculated from the radioactivity of cerebellum as an input function. The exponential decrease of the k3 value with aging was observed. The k3 value of the youngest subject (22 years old, male) was 0.035/min, while that of the oldest one (72 years old, male) was found to be 0.020/min. These data suggested that the dopaminergic activity through D2 dopamine receptors reduces with aging in human striatum.

Adult↗

[Valvular regurgitation in patients with Kawasaki disease and in healthy children: a pulsed Doppler echocardiographic study].

Valvular lesions in the acute stage of Kawasaki disease were observed using pulsed Doppler echocardiography. The subjects consisted of 65 patients with Kawasaki disease (2 months-6 2/12 years) who had been followed from the acute stage. The age-matched 113 controls were selected from 661 healthy children (2 months-14 years of age). In the acute stage of Kawasaki disease, tricuspid regurgitation (TR) was detected in 31 (48%), pulmonary regurgitation (PR) in 22 (34%) and mitral regurgitation (MR) in 17 (26%). There was no aortic regurgitation (AR). In the convalescent stage, TR was found in 26 (40%), PR in 20 (31%), and MR in 11 (17%), but no AR was detected. The incidence of each valvular regurgitation between the acute and convalescent stages in patients with Kawasaki disease did not differ significantly. Furthermore, there was no significant difference in the incidence of valvular regurgitation between patients with Kawasaki disease and the normal controls. In nine patients, however, valvular regurgitation in the acute stage had disappeared by the convalescent stage, and two patients had developed a new pansystolic murmur in the acute stage. We estimated the incidence of pathologic valvular involvement in Kawasaki disease to be 11/65 (17%). The incidence of valvular involvement in patients with coronary artery aneurysms was significantly higher than that of patients without coronary artery aneurysms (p less than 0.01). It was concluded that mild and transient valvular regurgitation, which cannot be detected by auscultation, may occur in some patients in the acute stage of Kawasaki disease. These may be caused by acute inflammation of the valve related to coronary artery lesions. In view of the Doppler echocardiographic findings in normal controls, these regurgitations should be distinguished from "physiological" ones.

Acute Disease↗

Blood lead levels of the general populations of three Chinese cities.

Blood samples were obtained from 537 adults (age greater than or equal to 16 years) living in three cities in China; in Hefei in 1985, and in Shenyang and Jinxi in 1987. The samples were subjected to blood lead (Pb-B) analyses. The subjects were factory workers either in solvent-synthesizing or solvent application plants with no known exposure to metals (including lead). Their smoking and drinking habits were confirmed in medical interviews. Blood lead was significantly higher in smokers than in non-smokers, although no dose-dependency was observed. The Pb-B values in non-smokers were log-normally distributed. The Pb-B among non-smokers was significantly higher in men [104.0 micrograms l-1 (1.428) 87] [geometric mean (geometric standard deviation) number of determinations] than in women [75.5 micrograms l-1 (1.358) 225] when the data from the three cities were combined. There was a significant difference in the Pb-B levels of non-smoking men in the three cities studied, suggesting that regional food habits should be considered as a possible contributory factor of a non-occupational nature. The present findings are compared with observations from Korea and Japan from the viewpoint of environmental health.

China↗