Teruhiko Kido

Biological monitoring of cadmium exposure in itai-itai disease epidemiology

SummaryCadmium (Cd) concentrations in blood and urine were significantly higher in itai-itai disease patients, suspected patients and inhabitants in Cd-polluted areas in Japan. Urinary Cd concentrations were mainly related to the body burden of Cd and did not decrease for several years following cessation of Cd exposure. There was a close association between urinary Cd excretion and the occurrence of ß2 microglobulinuria (ß2- mg-uria). Probit regression analysis between urinary Cd excretion and, ß2-mg-uria indicated that the threshold value may be set around 4 μg/g creatinine (cr.). Studies on inhabitants in Cd-polluted areas showed that urinary, ß2-mg levels of more than 1000 μg/l or 1000 μg/g cr. were irreversible, while increased urinary excretion of ß2-mg was associated with increased mortality. At present, ß2-mg in urine is not a suitable indicator for monitoring renal tubular dysfunction in the general population since the significance of slightly increased excretion of urinary ß2-mg has yet to be clarified.

Dose-Response Relationship between Urinary Cadmium Concentration and β2–Microglobulinuria Using Logistic Regression Analysis

Abstract Logistic regression analysis was used to investigate the dose-response relationship for environmental cadmium exposure and to consider the effect age had on this association. The target population comprised 3 178 inhabitants of Japan who were more than 50 y of age and who lived in a cadmium-polluted area and 1 134 inhabitants who lived in nonpolluted areas of Japan. Logistic regression analysis was completed on the dose-response relationship between urinary cadmium concentration (i.e., an indicator of cadmium body burden) and β2–microglobulinuria (i.e., an index of renal tubular dysfunction caused by exposure to cadmium). Both age and urinary cadmium concentration were associated significantly with β2-microglobulinuria. Based on the relationship that was determined, we calculated, by age and sex, the values of urinary cadmium concentration that corresponded to the prevalence rates of β2-microglobulinuria in the nonpolluted population. The resulting values were 1.6–3.0 μg/g creatinine for men and ...

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.

Dose-response relationship between total cadmium intake and β2-microglobulinuria using logistic regression analysis

Abstract The dose-response relationship between total cadmium intake and β 2 -microglobulinuria was investigated using logistic regression analysis in order to consider the effect of age on this association. The target population consisted of 1850 inhabitants of the cadmium-polluted Kakehashi River basin in Ishikawa prefecture, Japan. They were divided into 58 subgroups (27 in the men and 31 in the women) by four factors of sex, age, rice cadmium concentration and length of residence in cadmium-polluted areas. Logistic regression analysis was performed for this dose-response relationship, and both age and total cadmium intake were significantly associated with β 2 -microglobulinuria. It was confirmed that total cadmium intake had a significant association with β 2 -microglobulinuria, independent of the aging effect.

Ten-year follow-up study on the relation between the development of non-insulin-dependent diabetes mellitus and occupation.

To investigate the relation between occupation and the development of non-insulin-dependent diabetes mellitus (NIDDM), we undertook a 10-year follow-up survey of male employees of a zipper and aluminum sash factory in Japan. Of 1,218 employees we followed 1,087 subjects. We classified the subjects into five occupations: managers, technical workers, clerical workers, workers in transport, and laborers. NIDDM incidence was 3.1% for 10 years. The age-adjusted incidence of the workers in transport was the highest and that in laborers was the lowest. We used a multiple logistic analysis for adjustment with baseline characteristics such as age, BMI, fasting plasma glucose, and family history of diabetes mellitus. Adjusted relative risk of the workers in transport compared with the laborers was significantly high (3.95). Our work suggests that occupation is related to the development of NIDDM.

2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam.

Dioxin levels in the breast milk of mothers residing near a contaminated former airbase in Vietnam remain much higher than in unsprayed areas, suggesting high perinatal dioxin exposure for their infants. The present study investigated the association of perinatal dioxin exposure with autistic traits in 153 3-year-old children living in a contaminated area in Vietnam. The children were followed up from birth using the neurodevelopmental battery Bayley-III. The high-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed groups (⩾3.5u2009pg per g fat) showed significantly higher Autism Spectrum Rating Scale (ASRS) scores for both boys and girls than the mild-TCDD exposed groups, without differences in neurodevelopmental scores. In contrast, the high total dioxin-exposed group, indicated by polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs)—the toxic equivalents (TEQ) levels⩾17.9u2009pg-TEQ per g fat, had significantly lower neurodevelopmental scores than the mild-exposed group in boys, but there was no difference in the ASRS scores. The present study demonstrates a specific impact of perinatal TCDD on autistic traits in childhood, which is different from the neurotoxicity of total dioxins (PCDDs/Fs).

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.

Exercise blood pressure in young adults as a predictor of future blood pressure: a 12-year follow-up of medical school graduates.

It has not been fully clarified whether exercise blood pressure (BP) in young adult men and women is useful to predict future BP, especially in Asian people. A long-term prospective study was conducted in graduates of a medical school in Japan; 138 men and 76 women whose mean age was 19.8 and 19.2, respectively, at baseline. A 5-min exercise tolerance test was performed at baseline, and BP immediately after exercise was measured. BP at 50% intensity exercise was also calculated. Multiple regression analysis was carried out to clarify the relationship of exercise BP at baseline to follow-up BP after an average of 12 years. In multivariate-adjusted models, the relationship of systolic blood pressure (SBP) at follow-up was stronger to SBP immediately after exercise (F=7.7, P=0.006) than to resting SBP (F=3.7, P=0.055) in men. The models in men showed that SBP immediately after exercise was a stronger predictor of follow-up SBP than SBP at 50% intensity exercise, and the results were similar for diastolic blood pressure (DBP) in men. For SBP in women, resting SBP was the strongest predictor of follow-up SBP (F=14.3, P<0.001), and exercise SBP was not significant predictor. For DBP in women, any DBP at rest or after exercise was not significantly related to DBP at follow-up. In young adult men, SBP and DBP immediately after exercise would be a stronger predictor of future SBP and DBP rather than BP at rest. However, in young adult women, resting SBP rather than exercise SBP would be better to predict future SBP.

High cortisol and cortisone levels are associated with breast milk dioxin concentrations in Vietnamese women

OBJECTIVEnDioxin (polychlorinated dibenzodioxins+polychlorinated dibenzofurans) is one of the most toxic chemical substances known. Although it is suspected to cause endocrine disruption, very few epidemiological studies have been carried out on its effects on human steroid hormones. The aim of this study was to elucidate the association of dioxin exposure with steroid hormone levels in the saliva and serum of Vietnamese women.nnnSTUDY DESIGNnTwo areas, namely Phu Cat (hot spot) and Kim Bang (nonexposed area), were selected for the study. The study subjects consisted of 51 and 58 women respectively. Saliva, blood, and breast milk samples were collected from the subjects in both the areas.nnnMETHODSnCortisol, cortisone, DHEA, androstenedione, estrone, and estradiol levels in serum and saliva were determined by liquid chromatography-tandem mass spectrometry; dioxin concentrations in breast milk were measured by gas chromatography-mass spectrometry.nnnRESULTSnDioxin concentrations in the breast milk of women from the dioxin hot spot were three to four times higher than those in the breast milk of women from the nonexposed area. Good correlations were found between the levels of six steroid hormones in saliva and those in serum respectively. Salivary and serum cortisol and cortisone levels in women from the dioxin hot spot were significantly higher than those in women from the nonexposed area (P<0.001) and those in all the subjects were positively associated with dioxin concentrations in Vietnamese women (P<0.01).nnnCONCLUSIONnThese results suggest that dioxin influences steroidogenesis in humans. Saliva samples can be used for hormone analysis and are therefore excellent specimens in epidemiological studies.

Increased urinary β2-microglobulin and mortality rate by cause of death in a Cadmium-polluted area.

To clarify the effect of environmental cadmium (Cd) exposure on the life prognosis of inhabitants living in a Cd-polluted area, the standardized mortality ratio (SMR) according to cause of death in urinary β 2-microglobulin (β2-MG)-positive subjects (≥1000 μg/gCr) was compared to that of the Japanese general population and β2-MG-negative subjects (β 1000 μg/gCr).The SMR for all causes of death of both sexes was higher than that of the Japanese general population and β 2-MG-negative subjects. Among women, the SMR for malignant neoplasms was higher than that of β 2-MG-negative subjects. For cardiovascular disease and cerebrovascular disease, especially heart failure and cerebral infarction, SMRs were significantly higher in both sexes. The SMR for renal diseases was significantly high in the men and tended to be high in the women.These results suggest that the prognosis of urinary β 2-MG-positive subjects with Cd-induced renal tubular dysfunction is unfavorable, with higher mortality rates due to renal diseases, cerebral infarction and heart failure contributing to this. Although the increase of the mortality rate was slight, Cd might affect cancer mortality in women.