Background-Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. This study further examined the biological gradient between ingested inorganic arsenic and carotid atherosclerosis. Methods and Results-We studied 199 male and 264 female adult residents from the southwestern area of endemic arseniasis in Taiwan. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Diabetes mellitus was determined by oral glucose tolerance test, hypertension by mercury sphygmomanometers, and serum lipid profiles by autoanalyzers. Information regarding the consumption of high-arsenic artesian well water, cigarette smoking, and alcohol consumption was obtained through standardized questionnaire interviews. Logistic regression analysis was used to estimate the odds ratio and its 95% CI of carotid atherosclerosis for various risk factors. Three indices of long-term exposure to ingested arsenic, including the duration of consuming artesian well water, the average arsenic concentration in consumed artesian well water, and cumulative arsenic exposure, were all significantly associated with prevalence of carotid atherosclerosis in a dose-response relationship. The biological gradient remained significant after adjustment for age, sex, hypertension, diabetes mellitus, cigarette smoking, alcohol consumption, waist-to-hip ratio, and serum levels of total cholesterol and LDL cholesterol. The multivariate-adjusted odds ratio was 3.1 (95% CI 1.3 to 7.4) for those who had a cumulative arsenic exposure of Ն20 mg/L-years compared with those without exposure to arsenic from drinking artesian well water. Conclusions-Carotid atherosclerosis is associated with ingested inorganic arsenic, showing a significant biological

Abstract-The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age-and body mass index-adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: Ն19%) in women with PCOS increased the risk of elevated blood pressure (SBP Ն130 mm Hg and/or DBP Ն85 mm Hg) with an odds ratio of 3.817 (Pϭ0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia. Key Words: polycystic ovary syndrome Ⅲ testosterone Ⅲ systolic blood pressure Ⅲ diastolic blood pressure Ⅲ hypertension W omen with polycystic ovary syndrome (PCOS) are characterized by clinical and/or biochemical hyperandrogenism, oligomenorrhea, and the presence of polycystic ovaries. 1 PCOS is a heterogenous medical condition. Because large individual variation is present with respect to hyperandrogenism in terms of clinical manifestations and biochemistry, not all women with PCOS have elevated testosterone levels. Indeed, some women with PCOS without elevated testosterone levels may have acne, hirsutism, and/or androgenic alopecia that may arise as a result of the elevated androgens secreted by adipose tissue and the adrenal glands rather than the testosterone secreted from the ovaries.Although the increased risk of atherosclerotic cardiovascular disease and hypertension in women with PCOS remains controversial, 2,3 a variety of intriguing metabolic disturbances related to the risk for cardiovascular disease and hypertension are commonly found in a large proportion of women with PCOS, such as obesity, insulin resistance, dyslipidemia, and the metabolic syndrome. 4 Women with PCOS have been reported to have reduced vascular compliance, 5 vascular endothelial...

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The evidence linking arsenic in drinking water with increased urinary cancer risk comes from populations in relatively high exposure areas (>100 μg/L), whereas studies from lower exposure areas (<100 μg/L) reported inconsistent results. A previous study conducted in northeastern Taiwan, where residents were exposed to relatively lower concentrations, reported increased risk of urinary cancer in a dose-response way. Using the same cohort with longer follow-up, we conducted analysis to elucidate the relationship between ingested arsenic and urinary cancer in lower exposure groups and assessed the influence of duration, recency, and latency of drinking arsenic-containing well water. A total of 8,086 residents from northeastern Taiwan were followed for 12 years. Incident urinary cancer was ascertained through linkage with the national cancer registry. All analysis was done by Cox proportional hazards regression models. There were 45 incidences of urinary cancer and a monotonic increased risk of urinary cancer was found with increasing arsenic concentration (P < 0.001). For the highly exposed (>100 μg/L), the relative risks (RR) were >5-fold, whereas the risk was elevated but not significant for low exposure (<100 μg/L). Relative to the arsenic concentration <10 μg/L, those who drank well water with higher concentration from birth [RR, 3.69; 95% confidence interval (95% CI), 1.31-10.4], still drank at enrollment (RR, 3.50; 95% CI, 1.33-9.22), and drank for >50 years (RR, 4.12; 95% CI, 1.48-11.5) had a significantly increased risk of urinary cancer. When restricted to urothelial carcinoma, all risk estimates including concentration and characteristics of well water consumption were higher.

Podocalyxin was initially identified in glomerular podocytes to critically maintain the structural and functional integrity of the glomerular ultrafiltrative apparatus. Lately, it has emerged as a malignant marker in tumors arising from a variety of tissue origins. By immunohistochemistry, we identified that 9.6% of renal cell carcinoma patients overexpress this protein. This subset of patients had significantly shorter disease-specific and overall survivals, and, importantly, we established podocalyxin overexpression as an independent prognostic factor for latent distant metastasis with multivariate analysis. Podocalyxin down-regulation by small interfering RNA led to defective migration in model renal tubular cells, which was corrected by re-expression of podocalyxin. The activity of the small GTPase Rac1, a wellcharacterized modulator of cell migration, was diminished by podocalyxin knock-down. Conversely , podocalyxin overexpression in human embryonic kidney cells up-regulated Rac1 activity, which depended on a complex formed by podocalyxin, ERMbinding phosphoprotein 50, ezrin, and ARHGEF7, a Rac1 activator. Therefore, podocalyxin can serve as a biomarker to identify renal cell carcinoma patients with higher metastatic potential for more aggressive intervention at earlier clinical stages. (Am J Pathol

Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (> or =27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m(2) in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.

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Our results suggest that not only the AMH level, but also obesity, IR and elevated androgen levels may relate to the development of the large size of antral follicle pool and ovarian volume in women with PCOS. Obesity and IR may enhance the follicular excess through the dysregulation of AMH or through the pathway of hyperandrogenemia. These findings might partly explain why adequate body weight management and improvement in IR can improve the ovulatory function for women with PCOS.