Amarasiriwardena, Chitra

Person:
Amarasiriwardena, Chitra

Last Name

Amarasiriwardena

First Name

Chitra

Name

Amarasiriwardena, Chitra

Full item page

Search Results

Now showing 1 - 10 of 10

Associations of Toenail Arsenic, Cadmium, Mercury, Manganese, and Lead with Blood Pressure in the Normative Aging Study
(National Institute of Environmental Health Sciences, 2012) Mordukhovich, Irina; Wright, Robert; Hu, Howard; Amarasiriwardena, Chitra; Baccarelli, Andrea; Litonjua, Augusto A.; Sparrow, David; Vokonas, Pantel; Schwartz, Joel
Background: Arsenic, cadmium, mercury, and lead are associated with cardiovascular disease in epidemiologic research. These associations may be mediated by direct effects of the metals on blood pressure (BP) elevation. Manganese is associated with cardiovascular dysfunction and hypotension in occupational cohorts.: Objectives: We hypothesized that chronic arsenic, cadmium, mercury, and lead exposures elevate BP and that manganese lowers BP.: Methods: We conducted a cross-sectional analysis of associations between toenail metals and BP among older men from the Normative Aging Study (n = 639), using linear regression and adjusting for potential confounders. Results: An interquartile range increase in toenail arsenic was associated with higher systolic BP [0.93 mmHg; 95% confidence interval (CI): 0.25, 1.62] and pulse pressure (0.76 mmHg; 95% CI: 0.22, 1.30). Positive associations between arsenic and BP and negative associations between manganese and BP were strengthened in models adjusted for other toenail metals.: Conclusions: Our findings suggest associations between BP and arsenic and manganese. This may be of public health importance because of prevalence of both metal exposure and cardiovascular disease. Results should be interpreted cautiously given potential limitations of toenails as biomarkers of metal exposure.:
Associations of Early Childhood Manganese and Lead Coexposure with Neurodevelopment
(National Institute of Environmental Health Sciences, 2011) Henn, Birgit Claus; Schnaas, Lourdes; Lamadrid-Figueroa, Héctor; Hernández-Avila, Mauricio; Hu, Howard; Téllez-Rojo, Martha María; Ettinger, Adrienne; Schwartz, Joel; Amarasiriwardena, Chitra; Bellinger, David; Wright, Robert
Background: Most toxicologic studies focus on a single agent, although this does not reflect real-world scenarios in which humans are exposed to multiple chemicals. Objectives: We prospectively studied manganese–lead interactions in early childhood to examine whether manganese–lead coexposure is associated with neurodevelopmental deficiencies that are more severe than expected based on effects of exposure to each metal alone. Methods: Four hundred fifty-five children were enrolled at birth in an longitudinal cohort study in Mexico City, provided blood samples, and were followed until 36 months of age. We measured lead and manganese at 12 and 24 months and assessed neurodevelopment at 6-month intervals from 12 to 36 months of age using Bayley Scales of Infant Development–II. Results: Mean (± SD) blood concentrations at 12 and 24 months were, respectively, 24.7 ± 5.9 μg/L and 21.5 ± 7.4 μg/L for manganese and 5.1 ± 2.6 μg/dL and 5.0 ± 2.9 μg/dL for lead. Mixed-effects models, including Bayley scores at five time points, showed a significant interaction over time: highest manganese quintile × continuous lead; mental development score, β = –1.27 [95% confidence interval (CI): –2.18, –0.37]; psychomotor development score, β = –0.92 (95% CI: –1.76, –0.09). Slopes for the estimated 12-month lead effect on 18-month mental development and 24- through 36-month psychomotor development scores were steeper for children with high manganese than for children with midrange manganese levels. Conclusions: We observed evidence of synergism between lead and manganese, whereby lead toxicity was increased among children with high manganese coexposure. Findings highlight the importance of understanding health effects of mixed exposures, particularly during potentially sensitive developmental stages such as early childhood.
Levels of Lead in Breast Milk and Their Relation to Maternal Blood and Bone Lead Levels at One Month Postpartum.
(National Institute of Environmental Health Sciences, 2004) Téllez-Rojo, Martha María; González-Cossío, Teresa; Aro, Antonio; Hu, Howard; Hernández-Avila, Mauricio; Ettinger, Adrienne; Amarasiriwardena, Chitra; Peterson, Karen
Despite the many well-recognized benefits of breast-feeding for both mothers and infants, detectable levels of lead in breast milk have been documented in population studies of women with no current environmental or occupational exposures. Mobilization of maternal bone lead stores has been suggested as a potential endogenous source of lead in breast milk. We measured lead in breast milk to quantify the relation between maternal blood and bone lead levels and breast-feeding status (exclusive vs. partial) among 310 lactating women in Mexico City, Mexico, at 1 month postpartum. Umbilical cord and maternal blood samples were collected at delivery. Maternal breast milk, blood, and bone lead levels were obtained at 1 month postpartum. Levels of lead in breast milk ranged from 0.21 to 8.02 microg/L (ppb), with a geometric mean (GM) of 1.1 microg/L; blood lead ranged from 1.8 to 29.9 microg/dL (GM = 8.4 microg/dL); bone lead ranged from less than 1 to 67.2 microg/g bone mineral (patella) and from less than 1 to 76.6 microg/g bone mineral (tibia) at 1 month postpartum. Breast milk lead was significantly correlated with umbilical cord lead [Spearman correlation coefficient (r\(_S\)) = 0.36, p less than 0.0001] and maternal blood lead (r\(_S\)= 0.38, p less than 0.0001) at delivery and with maternal blood lead (r\(_S\) = 0.42, p less than 0.0001) and patella lead (r\(_S\)= 0.15, p less than 0.01) at 1 month postpartum. Mother's age, years living in Mexico City, and use of lead-glazed ceramics, all predictive of cumulative lead exposure, were not significant predictors of breast milk lead levels. Adjusting for parity, daily dietary calcium intake (milligrams), infant weight change (grams), and breast-feeding status (exclusive or partial lactation), the estimated effect of an interquartile range (IQR) increase in blood lead (5.0 microg/dL) was associated with a 33% increase in breast milk lead [95% confidence interval (CI), 24 to 43%], whereas an IQR increase in patella lead (20 microg/g) was associated with a 14% increase in breast milk lead (95% CI, 5 to 25%). An IQR increase in tibia lead (12.0 microg/g) was associated with a 5% increase in breast milk lead (95% CI, -3% to 14%). Our results indicate that even among a population of women with relatively high lifetime exposure to lead, levels of lead in breast milk are low, influenced both by current lead exposure and by redistribution of bone lead accumulated from past environmental exposures.
A Child with Chronic Manganese Exposure from Drinking Water
(U.S. Department of Health and Human Services & National Institute of Environmental Health Sciences, 2002) Woolf, Alan; Wright, Robert; Amarasiriwardena, Chitra; Bellinger, David
The patient's family bought a home in a suburb, but the proximity of the house to wetlands and its distance from the town water main prohibited connecting the house to town water. The family had a well drilled and they drank the well water for 5 years, despite the fact that the water was turbid, had a metallic taste, and left an orange-brown residue on clothes, dishes, and appliances. When the water was tested after 5 years of residential use, the manganese concentration was elevated (1.21 ppm; U.S. Environmental Protection Agency reference, < 0.05 ppm). The family's 10-year-old son had elevated manganese concentrations in whole blood, urine, and hair. The blood manganese level of his brother was normal, but his hair manganese level was elevated. The patient, the 10-year-old, was in the fifth grade and had no history of learning problems; however, teachers had noticed his inattentiveness and lack of focus in the classroom. Our results of cognitive testing were normal, but tests of memory revealed a markedly below-average performance: the patient's general memory index was at the 13th percentile, his verbal memory at the 19th percentile, his visual memory at the 14th percentile, and his learning index at the 19th percentile. The patient's free recall and cued recall tests were all 0.5-1.5 standard deviations (1 SD = 16th percentile) below normal. Psychometric testing scores showed normal IQ but unexpectedly poor verbal and visual memory. These findings are consistent with the known toxic effects of manganese, although a causal relationship cannot necessarily be inferred.
Demand for \(Zn^{2+}\) in Acid-Secreting Gastric Mucosa and Its Requirement for Intracellular \(Ca^{2+}\)
(Public Library of Science, 2011) Liu, JingJing; Kohler, Jonathan E.; Blass, Amy L.; Moncaster, Juliet A.; Mocofanescu, Anca; Marcus, Matthew A.; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Casey, Noel; Amarasiriwardena, Chitra; Goldstein, Lee E.; Soybel, David I.
Background and Aims: Recent work has suggested that \(Zn^{2+}\) plays a critical role in regulating acidity within the secretory compartments of isolated gastric glands. Here, we investigate the content, distribution and demand for \(Zn^{2+}\) in gastric mucosa under baseline conditions and its regulation during secretory stimulation. Methods and Findings: Content and distribution of zinc were evaluated in sections of whole gastric mucosa using X-ray fluorescence microscopy. Significant stores of \(Zn^{2+}\) were identified in neural elements of the muscularis, glandular areas enriched in parietal cells, and apical regions of the surface epithelium. In in vivo studies, extraction of the low abundance isotope, \(^{70}Zn^{2+}\), from the circulation was demonstrated in samples of mucosal tissue 24 hours or 72 hours after infusion (250 µg/kg). In in vitro studies, uptake of \(^{70}Zn^{2+}\) from media was demonstrated in isolated rabbit gastric glands following exposure to concentrations as low as 10 nM. In additional studies, demand of individual gastric parietal cells for \(Zn^{2+}\) was monitored using the fluorescent zinc reporter, fluozin-3, by measuring increases in free intracellular concentrations of \(Zn^{2+}\) \(\{[Zn^{2+}]_i\}\) during exposure to standard extracellular concentrations of \(Zn^{2+}\) (10 µM) for standard intervals of time. Under resting conditions, demand for extracellular \(Zn^{2+}\) increased with exposure to secretagogues (forskolin, carbachol/histamine) and under conditions associated with increased intracellular \(Ca^{2+}\) \(\{[Ca^{2+}]_i\}\). Uptake of \(Zn^{2+}\) was abolished following removal of extracellular \(Ca^{2+}\) or depletion of intracellular \(Ca^{2+}\) stores, suggesting that demand for extracellular \(Zn^{2+}\) increases and depends on influx of extracellular \(Ca^{2+}\). Conclusions: This study is the first to characterize the content and distribution of \(Zn^{2+}\) in an organ of the gastrointestinal tract. Our findings offer the novel interpretation, that \(Ca^{2+}\) integrates basolateral demand for \(Zn^{2+}\) with stimulation of secretion of HCl into the lumen of the gastric gland. Similar connections may be detectable in other secretory cells and tissues.
Maternal arsenic exposure and impaired glucose tolerance during pregnancy
(National Institute of Environmental Health Sciences, 2009) Ettinger, Adrienne; Zota, Ami R.; Amarasiriwardena, Chitra; Hopkins, Marianne; Schwartz, Joel; Hu, Howard; Wright, Robert
Background: Accumulating evidence has shown an increased risk of type 2 diabetes in general populations exposed to arsenic, but little is known about exposures during pregnancy and the association with gestational diabetes (GD). Objectives: We studied 532 women living proximate to the Tar Creek Superfund Site to investigate whether arsenic exposure is associated with impaired glucose tolerance during pregnancy. Methods: Blood glucose was measured between 24 and 28 weeks gestation after a 1-hr oral glucose tolerance test (GTT) as part of routine prenatal care. Blood and hair were collected at delivery and analyzed for arsenic using inductively coupled plasma mass spectrometry with dynamic reaction cell. Results: Arsenic concentrations ranged from 0.2 to 24.1 μg/L (ppb) (mean ± SD, 1.7 ±1.5) and 1.1 to 724.4 ng/g (ppb) (mean ± SD, 27.4 ± 61.6) in blood and hair, respectively. One-hour glucose levels ranged from 40 to 284 mg/dL (mean ± SD, 108.7 ± 29.5); impaired glucose tolerance was observed in 11.9% of women when using standard screening criterion (> 140 mg/dL). Adjusting for age, Native-American race, prepregnancy body mass index, Medicaid use, and marital status, women in the highest quartile of blood arsenic exposure had 2.8 higher odds of impaired GTT than women in the lowest quartile of exposure (95% confidence interval, 1.1–6.9) (p-trend = 0.008). Conclusions: Among this population of pregnant women, arsenic exposure was associated with increased risk of impaired GTT at 24–28 weeks gestation and therefore may be associated with increased risk of GD.
Association between 24-Hour Urinary Cadmium and Pulmonary Function among Community-Exposed Men: The VA Normative Aging Study
(National Institute of Environmental Health Sciences, 2008) Lampe, Brad J.; Park, Sung Kyun; Robins, Thomas; Mukherjee, Bhramar; Litonjua, Augusto A.; Amarasiriwardena, Chitra; Weisskopf, Marc; Sparrow, David; Hu, Howard
Background: High levels of cadmium exposure are known to cause emphysema in occupationally exposed workers, but little has been reported to date on the association between chronic environmental cadmium exposure and pulmonary function. Objective: In this study we examined the association between pulmonary function and cadmium body burden in a subcohort of the Normative Aging Study, a community-based study of aging. Methods: We examined 96 men who had cadmium measured in single 24-hr urinary specimens collected in 1994–1995 and who had one to three tests of pulmonary function between 1994 and 2002 (a total of 222 observations). We used mixed-effect models to predict pulmonary function based on individual 24-hr urinary cadmium output, adjusted for age, height, time elapsed from the baseline, and smoking status. We assessed effect modification by smoking status. Results: Among all subjects, a single log-unit increase in baseline urinary cadmium was inversely associated with forced expiratory volume in 1 sec (FEV1) percent predicted [β = −7.56%; 95% confidence interval (CI) −13.59% to −1.53%]; forced vital capacity (FVC) percent predicted (β = −2.70%; 95% CI −7.39% to 1.99%), and FEV1/FVC ratio (β = −4.13%; 95% CI −7.61% to −0.66%). In models including an interaction between urinary cadmium and smoking status, there was a graded, statistically significant reduction in FEV1/FVC ratio across smoking status in association with urinary cadmium. Conclusions: This study suggests that chronic cadmium exposure is associated with reduced pulmonary function, and cigarette smoking modifies this association. These results should be interpreted with caution because the sample size is small, and further studies are needed to confirm our findings.
Lead, Diabetes, Hypertension, and Renal Function: The Normative Aging Study
(National Institue of Environmental Health Sciences, 2004) Tsaih, Shirng-Wern; Korrick, Susan; Schwartz, Joel; Amarasiriwardena, Chitra; Aro, Antonio; Sparrow, David; Hu, Howard
In this prospective study, we examined changes in renal function during 6 years of follow-up in relation to baseline lead levels, diabetes, and hypertension among 448 middle-age and elderly men, a subsample of the Normative Aging Study. Lead levels were generally low at baseline, with mean blood lead, patella lead, and tibia lead values of 6.5 μg/dL, 32.4 μg/g, and 21.5 μg/g, respectively. Six percent and 26% of subjects had diabetes and hypertension at baseline, respectively. In multivariate-adjusted regression analyses, longitudinal increases in serum creatinine (SCr) were associated with higher baseline lead levels but these associations were not statistically significant. However, we observed significant interactions of blood lead and tibia lead with diabetes in predicting annual change in SCr. For example, increasing the tibia lead level from the midpoints of the lowest to the highest quartiles (9–34 μg/g) was associated with an increase in the rate of rise in SCr that was 17.6-fold greater in diabetics than in nondiabetics (1.08 mg/dL/10 years vs. 0.062 mg/dL/10 years; p < 0.01). We also observed significant interactions of blood lead and tibia lead with diabetes in relation to baseline SCr levels (tibia lead only) and follow-up SCr levels. A significant interaction of tibia lead with hypertensive status in predicting annual change in SCr was also observed. We conclude that longitudinal decline of renal function among middle-age and elderly individuals appears to depend on both long-term lead stores and circulating lead, with an effect that is most pronounced among diabetics and hypertensives, subjects who likely represent particularly susceptible groups.
Effect of breast milk lead on infant blood lead levels at 1 month of age
(National Institue of Environmental Health Sciences, 2004) Ettinger, Adrienne; Téllez-Rojo, Martha María; Amarasiriwardena, Chitra; Bellinger, David; Peterson, Karen; Schwartz, Joel; Hu, Howard; Hernández-Avila, Mauricio
Nursing infants may be exposed to lead from breast milk, but relatively few data exist with which to evaluate and quantify this relationship. This route of exposure constitutes a potential infant hazard from mothers with current ongoing exposure to lead as well as from mothers who have been exposed previously due to the redistribution of cumulative maternal bone lead stores. We studied the relationship between maternal breast milk lead and infant blood lead levels among 255 mother–infant pairs exclusively or partially breast-feeding through 1 month of age in Mexico City. A rigorous, well-validated technique was used to collect, prepare, and analyze the samples of breast milk to minimize the potential for environmental contamination and maximize the percent recovery of lead. Umbilical cord and maternal blood lead were measured at delivery; 1 month after delivery (± 5 days) maternal blood, bone, and breast milk and infant blood lead levels were obtained. Levels of lead at 1 month postpartum were, for breast milk, 0.3–8.0 μg/L (mean ± SD, 1.5 ± 1.2); maternal blood lead, 2.9–29.9 μg/dL (mean ± SD, 9.4 ± 4.5); and infant blood lead, 1.0–23.1 μg/dL (mean ± SD, 5.5 ± 3.0). Infant blood lead at 1 month postpartum was significantly correlated with umbilical cord (Spearman correlation coefficient rS = 0.40, p < 0.0001) and maternal (rS = 0.42, p < 0.0001) blood lead at delivery and with maternal blood (rS = 0.67, p < 0.0001), patella (rS = 0.19, p = 0.004), and breast milk (rS = 0.32, p < 0.0001) lead at 1 month postpartum. Adjusting for cord blood lead, infant weight change, and reported breast-feeding status, a difference of approximately 2 μg/L (ppb; from the midpoint of the lowest quartile to the midpoint of the highest quartile) breast milk lead was associated with a 0.82 μg/dL increase in blood lead for breast-feeding infants at 1 month of age. Breast milk lead accounted for 12% of the variance of infant blood lead levels, whereas maternal blood lead accounted for 30%. Although these levels of lead in breast milk were low, they clearly have a strong influence on infant blood lead levels over and above the influence of maternal blood lead. Additional information on the lead content of dietary alternatives and interactions with other nutritional factors should be considered. However, because human milk is the best and most complete nutritional source for young infants, breast-feeding should be encouraged because the absolute values of the effects are small within this range of lead concentrations.
Maternal Fish Consumption, Hair Mercury, and Infant Cognition in a U.S. Cohort
(National Institute of Environmental Health Sciences, 2005) Oken, Emily; Wright, Robert; Kleinman, Kenneth Paul; Bellinger, David; Amarasiriwardena, Chitra; Hu, Howard; Rich-Edwards, Janet; Gillman, Matthew
Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother–infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9–92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, –13.7 to –1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels ≤1.2 ppm. Higher fish consumption in pregnancy was associated with better infant cognition, but higher mercury levels were associated with lower cognition. Women should continue to eat fish during pregnancy but choose varieties with lower mercury contamination.