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Biomedical subjects

K Nogawa

Publications and source records attributed to K Nogawa.

At least 19 recordsLinked to original sources

Significance of elevated urinary human intestinal alkaline phosphatase in Japanese people exposed to environmental cadmium.

Urinary human intestinal alkaline phosphatase (IAP), beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cd-exposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between beta 2-MG and IAP or NAG. The beta 2-MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and beta 2-MG is considered to be more useful.

Acetylglucosaminidase

The renal handling of sodium and potassium in environmental cadmium-exposed subjects with renal dysfunction.

To clarify using clearance methods the renal handling of sodium and potassium in a population with environmental cadmium (Cd)-induced renal dysfunction, 76 Cd-exposed subjects (32 men and 44 women) and 36 non-exposed subjects (18 men and 18 women) were selected. Fractional excretions of potassium and beta 2-microglobulin were higher in the Cd-exposed subjects than in the non-exposed subjects, while the fractional excretion of sodium in the Cd-exposed subjects was equal to that of the non-exposed subjects. The urinary excretion rate of sodium was significantly lower in the Cd-exposed subjects than in the non-exposed subjects, while no significant difference was found in the urinary potassium excretion rate. Fractional excretion of sodium showed a significant correlation with age in all the subjects, while that of potassium significantly correlated with serum beta 2-microglobulin. These results indicate that increases in the fractional excretion of sodium or potassium do not directly signify increased urinary excretion of sodium or potassium in Cd-induced renal tubular dysfunction. The fractional excretion of potassium may be more affected by Cd-induced renal dysfunction, while that of sodium appears to be more related to age.

Aged

Impairment of vitamin D metabolism due to environmental cadmium exposure, and possible relevance to sex-related differences in vulnerability to the bone damage.

To determine whether depleted serum 1 alpha,25-dihydroxyvitamin D (VD) concentrations are associated with cadmium (Cd)-induced renal damage, the relationships between four indices of renal function and two indicators of bone metabolism, that is, serum VD and parathyroid hormone (PTH) concentrations, were analyzed in 30 male and 44 female subjects exposed to environmental Cd. Also, these associations were compared in male and female subjects to evaluate sex-related differences in vulnerability to the bone damage observed in Cd-exposed persons. Serum VD decreased significantly with declines in creatinine clearance and percentage tubular reabsorption of phosphate, and with increases in serum creatinine and serum beta 2-microglobulin (beta 2m) concentrations in the female subjects exposed to Cd, but not in the male subjects. The correlation between serum VD and PTH levels was also significant only in the females. Correlation coefficients between serum beta 2m and VD and those between serum PTH and VD in both sexes were significantly different. These results suggest that renal damage due to Cd exposure leads to the decreases in the serum VD level and increases in serum PTH level, and that the more marked changes in serum VD and PTH in the women may play a role in the development of sex-related differences in Cd-induced bone injury.

Aged

Dose-response relationship for renal dysfunction in a population environmentally exposed to cadmium.

Two epidemiological studies aimed at investigating the dose-response relationship of environmental cadmium exposure were performed in a population living in the Kakehashi River basin, a cadmium-polluted area in Japan. In the first, the average cadmium concentration in rice from each village was used as an indicator of exposure and metallothioneinuria or beta 2-microglobulinuria as an index of renal tubular dysfunction. Dose-related increases in both the latter indices were observed. The total cadmium intake resulting in both metallothioneinuria and beta 2-microglobulinuria was calculated to be approximately 2 g for both sexes. In the second study, the dose-response relationship between urinary cadmium and metallothioneinuria or beta 2-microglobulinuria was evaluated in the same population. Prevalence rates increased proportionally with increasing urinary cadmium (Cd-U). The values of Cd-U corresponding to the prevalence rates of metallothioneinuria in the non-exposed population were calculated to be 4.2 micrograms/g creatinine for men and 4.8 micrograms/g creatinine for women; for beta 2-microglobulinuria the corresponding figures were 3.8 micrograms/g creatinine for men and 4.1 micrograms/g creatinine for women.

Aged

Dose-response relationship between dietary cadmium intake and metallothioneinuria in a population from a cadmium-polluted area of Japan.

An epidemiological study to examine the dose-response relationship for environmental cadmium exposure was performed in 1843 cadmium-exposed and 240 non-exposed inhabitants of the Kakehashi River basin in Ishikawa, Japan. The average cadmium concentration in rice from each village was employed as an indicator of cadmium exposure and the individuals were grouped according to the length of residence in the polluted area. Metallothioneinuria was used as an index of renal tubular dysfunction produced by the chronic exposure to cadmium. A dose-related increase in metallothioneinuria was observed. The chronic total cadmium intake resulting in metallothioneinuria in this population was calculated to be approximately 2 g for both men and women. The cumulative lifetime dose of 2 g cadmium over a 50-year period, means an average daily intake of 110 micrograms. Thus, these values may be regarded as the maximum allowable lifetime and daily intake limits, respectively for chronic dietary exposure to cadmium.

Administration, Oral

Assessment of cadmium-induced osteopenia by measurement of serum bone Gla protein, parathyroid hormone, and 1 alpha,25-dihydroxyvitamin D.

To assess the osteopenia induced by environmental cadmium (Cd) exposure by measurement of serum bone Gla protein (BGP), parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)2D), 29 men and 41 women who lived in a Cd-polluted area and showed renal tubular dysfunction were selected. To evaluate the degree of osteopenia, microdensitometry (MD) was used. Compared with the non-exposed subjects, the levels of serum creatinine and BGP, urinary Cd and beta 2-microglobulin and blood Cd were higher, while the levels of serum inorganic phosphorus and MD indicators were lower in the Cd-exposed group. In simple correlation matrix, BGP showed significant correlations with serum alkaline phosphatase (S-Al-p) and MD indicators in the Cd-exposed men, and also correlations with S-Al-p and 1 alpha-25(OH)2D in the Cd-exposed women. Applying multivariate analysis to the Cd-exposed subjects, BGP, %TRP and base excess were found to show significant associations with the MD indicators in the men. In the women, PTH, age, blood Cd and BGP were associated significantly with the MD indicators. Only serum BGP showed a significant correlation in both sexes of the Cd-exposed subjects, and a sex difference was found in the relationship between bone metabolic markers and osteopenia. These results suggest that serum BGP has a close independent association with the osteopenia induced by Cd exposure and that BGP, which has a different biological function from that of PTH or 1 alpha,25(OH)2D, may be a useful indicator to detect bone damage in Cd-exposed subjects.

Adult

Dose-response relationship between urinary cadmium and metallothionein in a Japanese population environmentally exposed to cadmium.

The dose-response relationship between cadmium (Cd) exposure and renal dysfunction, as measured by urinary Cd and metallothoinein (MT), was evaluated in a population living in the Kakehashi River basin, a Cd-polluted area in Japan. Morning urine specimens were collected from 1397 men and 1713 women who were 50 years or older. In addition, urine specimens were collected from a control population consisting of 110 men and 130 women. The 97.5% upper limits for MT in the control population were used to determine the prevalence rates for MT-uria at various urinary Cd concentrations. Probit linear regression analysis showed significant dose-response relationships between MT and Cd. In the control population, prevalence rates of MT-uria for men and women were 1.8 and 3.1%, respectively. Based on the prevalence rates of MT-uria in the control population, the upper limits for the urinary Cd concentrations were calculated from the slopes of the regression lines to be 4.2 and 4.8 micrograms/g creatinine for men and women, respectively. These values, which are similar to those reported previously using urinary beta 2-microglobulin as the indicator, may be of use in establishing the biological threshold, i.e. maximum allowable concentration, for urinary Cd in the environmentally exposed Japanese population.

Age Factors

Significant increase of urinary mucoprotein in environmental-cadmium-exposed Japanese subjects.

Urinary mucoprotein (U-MP) was determined in 169 Japanese environmental-cadmium-exposed and 81 non-exposed subjects. Urinary total protein, albumin, beta 2-microglobulin (beta 2-MG), cadmium (Cd) and creatinine were also measured. Significant increases in U-MP and other proteins were found in the Cd-exposed subjects. Significant correlations between each protein were seen in the Cd-exposed and the total group of subjects. U-MP was highly correlated with urinary beta 2-MG and their correlation coefficient was the highest in the total group of subjects. beta 2-MG was the most sensitive indicator among them to detect Cd-induced renal dysfunction, although beta 2-MG is degraded in urine with a pH less than 5.5 U-MP is an acid-soluble protein. Therefore, U-MP is also available for studies on renal dysfunction caused by exposure to Cd, in conjunction with beta 2-MG.

Albuminuria

Serum vitamin D metabolites in cadmium-exposed persons with renal damage.

Serum concentrations of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1 alpha,25(OH)2D] were measured in ten cadmium (Cd)-exposed subjects and five non exposed subjects. The Cd-exposed subjects were divided into two groups according to serum 1 alpha,25(OH)2D levels. No significant differences for 25(OH)D were found between the Cd-exposed group with low or normal serum 1 alpha,25(OH)2D and the non exposed group. The concentrations of 24,25(OH)2D were the lowest in the Cd-exposed group with low serum 1 alpha,25(OH)2D, highest in the non exposed group, and significantly lower in the Cd-exposed group with normal serum 1 alpha,25(OH)2D than in the non exposed group. Renal function was much worse in the Cd-exposed group with low serum 1 alpha,25(OH)2D than in the group with normal serum 1 alpha,25(OH)2D. These findings indicate that Cd initially disturbs hydroxylation from 25(OH)D to 24,25(OH)2D and then disturbs hydroxylation from 25(OH)D to 1 alpha,25(OH)2D. The decrease of serum 24,25(OH)2D and 1 alpha,25(OH)2D in Cd-exposed subjects is not due to a decrease of the serum 25(OH)D level.

24,25-Dihydroxyvitamin D 3

Prevalence of metallothioneinuria among the population living in the Kakehashi River basin in Japan--an epidemiological study.

An epidemiological study to evaluate cadmium-induced renal dysfunction by urinary metallothionein levels was carried out in an environmentally-exposed Japanese population. The study population consisted of 3168 men and women from a cadmium-polluted area who were 50 years and older and 291 individuals from a non-polluted area. The mean metallothionein levels in urine of the control population were 138.2 +/- 2.1 and 198.6 +/- 1.9 microgram/g creatinine for men and women, respectively. The corresponding values for the cadmium-exposed population were 157.8 +/- 2.2 and 248.0 +/- 2.2. The 97.5% upper limits for men in the control population was determined to be 638 and for women 693 microgram MT/g creatinine. Based on these values as the cut-off levels, the prevalence of metallothioneinuria was calculated to be 4.6% in men and 8.4% in women from the cadmium-polluted area. Further selection of the population, based on life-time residence in the polluted area accompanied with the consumption of cadmium-containing rice, showed an even greater prevalence of metallothioneinuria: 5.4% in men and 10.9% in women of all ages. The prevalence of metallothioneinuria increased with age and duration of residence in the polluted area. These results suggest that metallothioneinuria can be used as an indicator of renal dysfunction due to environmental cadmium exposure.

Age Factors

The association between renal dysfunction and osteopenia in environmental cadmium-exposed subjects.

Two hundred and three cadmium (Cd)-exposed subjects with renal dysfunction and 80 non-exposed subjects were examined to reveal the relationship between Cd-induced renal dysfunction and osteopenia. As biological indicators of renal function, urinary beta 2-microglobulin (beta 2-mg), and serum creatinine, calcium, and phosphorus were selected. Cd in the urine and blood was also measured. The results indicated that significant differences exist between both sexes in Cd-exposed as well as nonexposed subjects. To evaluate the degree of osteopenia, a microdensitometrical (MD) method was used. The relationships between biological parameters and each index of the MD method were analyzed using multivariate analysis. Age, urinary beta 2-mg, and serum creatinine were significantly associated with indices of osteopenia in Cd-exposed men. In contrast, age showed the most significant association with MD indices in women of both groups. However, urinary beta 2-mg was significantly associated with MD indices only in Cd-exposed women. In Cd-exposed subjects, after the number of predictor variables was increased, urinary beta 2-mg was also strongly associated with osteopenia. These results suggest a causal relationship between renal dysfunction and osteopenia in Cd-exposed subjects.

Age Factors

Dose-response relationship between urinary cadmium and beta 2-microglobulin in a Japanese environmentally cadmium exposed population.

This study was carried out to test the dose-response relationship between urinary cadmium (Cd) and beta 2-microglobulin(beta 2-mg) and also to estimate the biological threshold value of urinary Cd concentration in inhabitants exposed to environmental Cd. Urinary Cd and beta 2-mg were measured in 3178 inhabitants over 50 years of age in the Cd-polluted Kakehashi River basin in Japan and 294 inhabitants in non-polluted areas. Urinary Cd and beta 2-mg were significantly higher in the Cd-exposed subjects than in the non-exposed subjects. Prevalence rates of beta 2-microglobulinuria(beta 2-mg-uria) increased proportionally with increasing urinary Cd concentrations and probit linear regression lines could be calculated between them. The urinary Cd concentration corresponding to the prevalence rates of beta 2-mg-uria among non-exposed subjects was calculated using the regression line, and values of 3.8-4.0 micrograms Cd/g creatinine for men and 3.8-4.1 micrograms Cd/g creatinine for women, respectively, were obtained. These values may be of use in establishing the biological threshold of urinary Cd concentration in environmentally Cd-exposed populations.

Aged

Osteopenia in inhabitants with renal dysfunction induced by exposure to environmental cadmium.

Bone density was measured in 28 women with itai-itai disease, 92 men and 114 women with cadmium-induced renal dysfunctions and 44 men and 66 women living in the three different non-polluted areas using a microdensitometer. The values of both indices corresponding to cortical width and bone mineral content were significantly lower in itai-itai disease patients than the cadmium-exposed women with renal dysfunctions and the non-exposed subjects. The cadmium-exposed women also showed a decrease in bone density compared with the non-exposed subjects. A significant decrease in bone density was also observed between cadmium-exposed men and the non-exposed subjects, although the difference was not as clear as in the women. The present study indicates that exposure to cadmium could cause marked osteopenia, particularly in the women.

Aged

A dose-response analysis of cadmium in the general environment with special reference to total cadmium intake limit.

An epidemiological study on the dose-response relationship of cadmium was performed on 1850 Cd-exposed and 294 nonexposed inhabitants of the Kakehashi River basin in Ishikawa Prefecture. beta 2-microglobulinuria was used as an index of the effect of cadmium on health and the average cadmium concentration in locally produced rice was employed as an indicator of cadmium exposure. Cadmium exposure was found to affect health in a dose-related manner when the subjects were classified according to the average cadmium concentration in their village rice and their length of residence in the polluted area. Based on the available data, the total cadmium intake that produced an adverse effect on health was calculated as approximately 2000 mg for both men and women.

Aged

Relationship between serum gamma-glutamyl transpeptidase activity, blood pressure and alcohol consumption.

The associations among alcohol consumption, gamma-glutamyl transpeptidase (gamma-GTP) activity in serum and blood pressure (BP) were analysed in a cross-sectional study of 1,156 healthy male workers 35 to 59 years of age, consisting of 349 non-drinkers, 682 light-daily drinkers (consuming less than 58 ml of alcohol per day) and 125 heavy-daily drinkers consuming more. No marked elevation of BP with high alcohol consumption was seen in the present subjects. On the other hand, a linear elevation of BP together with an increase in serum gamma-GTP activity was found in subjects above 40 years of age. The BP levels corresponding to the three different drinking habits, non-drinkers, light drinkers and heavy drinkers, were similar to each other regarding gamma-GTP levels. The relationship between gamma-GTP and BP was shown, by multiple regression analysis, to be independent of age, obesity and the dose of alcohol consumed. The contribution to the rise in BP of the dose of alcohol consumed, in comparison with that of gamma-GTP, was negligible. Serum gamma-GTP activity is a useful indicator of the susceptibility to the pressor effect of alcohol.

Adult

Leukocytosis and low serum IgA in workers exposed to the epoxy compound, t-methyl-3-phenylglycidate.

Forty-nine out of 54 male workers engaged in the production of an epoxy compound, t-methyl-3-phenylglycidate, showed skin symptoms in varying degrees that may be due to the skin-irritative effect of the compound. The exposed workers were also shown to have subjective symptoms which may be related to the irritative property of the compound on surface tissue. Laboratory examinations on the blood obtained from the exposed workers showed significantly higher values of leukocyte concentration as compared with the non-exposed controls. This was chiefly caused by the increase of neutrophilic granulocytes and T-cell lymphocytes. Serum IgA levels of the exposed workers were shown to be significantly lower than those of the control group. Hemoglobin concentration, hematocrit value and red cell count of the exposed workers remained at the same level as those of the control subjects. Liver or kidney damage was not found in biochemical analyses on the sera of exposed workers.

Adult