Objective: The effects of cadmium (Cd) on birth weight have been discussed in the scientific literature. However, investigations on the effects of maternal body burden of Cd on the next generation during pregnancy and lactation have been limited. The relation between maternal exposure to Cd and pregnancy outcome or Cd in breast milk in Japanese mothers was investigated. Methods: Cd concentrations in urine and colostrum milk samples of 57 mothers were measured by atomic absorption spectrophotometery. The relations between maternal urinary Cd and infant growth, gestational age at birth, and Cd in breast milk were investigated. Results: The rate of perterm deliveries of mothers with higher urinary Cd (>2 nmol/mmol creatinine (Cr)) was higher than that of mothers with lower urinary Cd (<2 nmol/mmol Cr). The gestational age was significantly correlated with urinary Cd even after adjustment for maternal age. The height and weight of newborn infants of mothers with higher urinary Cd were significantly lower than those of the newborn infants of mothers with lower urinary Cd, but these decreases were ascribed to early delivery induced by Cd. The Cd in breast milk of mothers with higher urinary Cd was significantly higher than that of mothers with lower urinary Cd. A significant positive correlation was found between maternal urinary Cd and Cd in breast milk. Conclusion: Maternal exposure to Cd seems to increase early delivery, which leads to a lower birth weight. Also, the Cd is transferred in part to the next generation through breast milk after birth.

A cross-sectional study on 6,676 workers consisting of 4,243 males and 2,433 females aged 20-58 yr in a metal product factory was conducted to elucidate the relationship between work characteristics, e.g. job demand/control/support, sedentary job, overtime work and shift work, and waist to hip ratio (WHR) as well as body mass index (BMI) taking alcohol consumption, smoking, exercise and other psychosocial factors such as education and marital status into account. By a stepwise multiple regression analysis, BMI was associated with shift work, marital status and sedentary job for males, and with exercise but inversely associated with education for females. WHR was also associated with shift work, alcohol consumption, marital status and sedentary job but inversely associated with exercise for males, and with sedentary job, marital status and education but inversely associated with smoking for females. These results suggest that work characteristics such as sedentary job and shift work should also be considered when trying to prevent increases in BMI and WHR.

Cardiac-specific overexpression of murine cardiac calsequestrin results in depressed cardiac contractile parameters, low Ca 2؉ -induced Ca 2؉ release from sarcoplasmic reticulum (SR) and cardiac hypertrophy in transgenic mice. To test the hypothesis that inhibition of phospholamban activity may rescue some of these phenotypic alterations, the calsequestrin overexpressing mice were cross-bred with phospholamban-knockout mice. Phospholamban ablation in calsequestrin overexpressing mice led to reversal of the depressed cardiac contractile parameters in Langendorff-perfused hearts or in vivo. This was associated with increases of SR Ca 2؉ storage, assessed by caffeine-induced Na ؉ -Ca 2؉ exchanger currents. The inactivation time of the L-type Ca 2؉ current (I Ca ), which has an inverse correlation with Ca 2؉ -induced SR Ca 2؉ release, and the relation between the peak current density and half-inactivation time were also normalized, indicating a restoration in the ability of I Ca to trigger SR Ca 2؉ release. The prolonged action potentials in calsequestrin overexpressing cardiomyocytes also reversed to normal upon phospholamban ablation. Furthermore, ablation of phospholamban restored the expression levels of atrial natriuretic factor and ␣-skeletal actin mRNA as well as ventricular myocyte size. These results indicate that attenuation of phospholamban function may prevent or overcome functional and remodeling defects in hypertrophied hearts.Hypertrophy of ventricular myocardium is postulated to be an adaptive response to relative increases in external workload, induced by endocrine, paracrine, autocrine, and mechanical factors or decreased myocardial contractility (1). The increase in heart mass has been implicated to normalize cardiac function by decreasing wall stress. However, a sustained imbalance between workload and muscle contractility may lead to progressive thinning of the left ventricular wall and chamber dilation associated with decompensated hypertrophy and heart failure (2, 3). Studies in human and animal models have shown that cardiac hypertrophy is associated with impaired sarcoplasmic reticulum (SR) 1 Ca 2ϩ modulation, leading to aberrant cardiac contraction and relaxation (4 -8). Although several Ca 2ϩ -related signaling molecules, such as calcineurin, Ca 2ϩ -calmodulin kinase, and Ca 2ϩ

On a viewpoint of gender differences in Cd body burden and its health effects, we reviewed the population-based research including our own which conducted in Japan, Thailand, Australia, Poland, Belgium and Sweden to assess health effects of human exposure to environmental cadmium and their potential mechanisms. As a result, six risk factors in Cd health effects in women have been identified; (1) more serious type of renal tubular dysfunction, (2) difference in calcium metabolism and its regulatory hormones, (3) kidney sensitivity; difference in P450 phenotype, (4) pregnancy, (5) body iron store status, and (6) genetic factors. Further studies of Cd toxicity targeted to women would now appear necessary.

We investigated the biological half-life of the urinary cadmium concentration (U-Cd) based on a 24-year follow-up study after cessation of cadmium exposure in a cadmium-polluted area. Spot urine samples were obtained from all inhabitants in this area in 1979, 1986, 1991, 1999 and 2003. Biological half-life was calculated in the inhabitants whose U-Cd was more than 5 microg l(-1) (9 men and 12 women) or 5 microg g(-1) creatinine (9 men and 19 women) using a one-compartment model. The estimated half-life and 95% confidence intervals were 13.6 years (9.0-28.2 years) and 13.9 years (9.6-25.6 years) for unadjusted U-Cd in men and women, respectively. For creatinine-adjusted U-Cd, they were 14.2 years (11.2-19.4 years) and 23.5 years (17.7-35.0 years) in men and women, respectively. The biological half-lives of U-Cd obtained in this study were identical with the values of total body burden determined by a different method.