Does Air Pollution Trigger Infant Mortality in Western Europe? A Case-Crossover Study

Background: Numerous studies show associations between fine particulate air pollutants [particulate matter with an aerodynamic diameter ≤ 10 μm (PM₁₀)] and mortality in adults.Objectives: We investigated short-term effects of elevated PM₁₀ levels on infant mortality in Flanders, Belgium, and studied whether the European Union (EU) limit value protects infants from the air pollution trigger.Methods: In a case-crossover analysis, we estimated the risk of dying from nontraumatic causes before 1 year of age in relation to outdoor PM₁₀ concentrations on the day of death. We matched control days on temperature to exclude confounding by variations in daily temperature.Results: During the study period (1998–2006), PM₁₀ concentration averaged 31.9 ± 13.8 μg/m³. In the entire study population (n = 2,382), the risk of death increased by 4% [95% confidence interval (CI), 0–8%; p = 0.045] for a 10-μg/m³ increase in daily mean PM₁₀. However, this association was significant only for late neonates (2–4 weeks of age; n = 372), in whom the risk of death increased by 11% (95% CI, 1–22%; p = 0.028) per 10-μg/m³ increase in PM₁₀. In this age class, infants were 1.74 (95% CI, 1.18–2.58; p = 0.006) times more likely to die on days with a mean PM₁₀ above the EU limit value of 50 μg/m³ than on days below this cutoff.Conclusions: Even in an affluent region in Western Europe, where infant mortality is low, days with higher PM air pollution are associated with an increased risk of infant mortality. Assuming causality, the current EU limit value for PM₁₀, which may be exceeded on 35 days/year, does not prevent PM₁₀ from triggering mortality in late neonates.     

A revised method for determination of dialkylphosphate levels in human urine by solid-phase extraction and liquid chromatography with tandem mass spectrometry: application to human urine samples from Japanese children

Objectives

Biological monitoring of organophosphorus insecticide (OP) metabolites, specifically dialkylphosphates (DAP) in urine, plays a key role in low-level exposure assessment of OP in individuals. The aims of this study are to develop a simple and sensitive method for determining four urinary DAPs using high-performance liquid chromatography with tandem mass spectrometry (LC–MS/MS), and to assess the concentration range of urinary DAP in Japanese children.

Methods

Deuterium-labeled DAPs were used as internal standards. Urinary dimethylphosphate (DMP) and diethylphosphate (DEP), which passed through the solid-phase extraction (SPE) column, and dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP), which were extracted from a SPE column using 2.5 % NH₃ water including 50 % acetonitrile, were prepared for separation analysis. The samples were then injected into LC–MS/MS. The optimized method was applied to spot urine samples from 3-year-old children (109 males and 116 females) living in Aichi Prefecture in Japan.

Results

Results from the validation study demonstrated good within- and between-run precisions (<10.7 %) with low detection limits (0.4 for DMP and DMTP, 0.2 for DEP and 0.1 μg/L for DETP). The geometric mean values and detection rates of the urinary DAPs in Japanese children were 14.4 μg/L and 100 % for DMP, 5.3 μg/L and 98 % for DMTP, 5.5 μg/L and 99 % for DEP, and 0.6 μg/L and 80 % for DETP, respectively.

Conclusions

The present high-throughput method is simple and reliable, and can thereby further contribute to development of an exposure assessment of OP. The present study is the first to reveal the DAP concentrations in young Japanese children.     

Validation of the shake test for detecting freeze damage to adsorbed vaccines

Objective

To determine the validity of the shake test for detecting freeze damage in aluminium-based, adsorbed, freeze-sensitive vaccines.

Methods

A double-blind crossover design was used to compare the performance of the shake test conducted by trained health-care workers (HCWs) with that of phase contrast microscopy as a “gold standard”. A total of 475 vials of 8 different types of World Health Organization prequalified freeze-sensitive vaccines from 10 different manufacturers were used. Vaccines were kept at 5 °C. Selected numbers of vials from each type were then exposed to −25 °C and −2 °C for 24-hour periods.

Findings

There was complete concordance between HCWs and phase-contrast microscopy in identifying freeze-damaged vials and non-frozen samples. Non-frozen samples showed a fine-grain structure under phase contrast microscopy, but freeze-damaged samples showed large conglomerates of massed precipitates with amorphous, crystalline, solid and needle-like structures. Particles in the non-frozen samples measured from 1 μm (vaccines against diphtheria–tetanus–pertussis; Haemophilus influenzae type b; hepatitis B; diphtheria–tetanus–pertussis–hepatitis B) to 20 μm (diphtheria and tetanus vaccines, alone or in combination). By contrast, aggregates in the freeze-damaged samples measured up to 700 μm (diphtheria–tetanus–pertussis) and 350 μm on average.

Conclusion

The shake test had 100% sensitivity, 100% specificity and 100% positive predictive value in this study, which confirms its validity for detecting freeze damage to aluminium-based freeze-sensitive vaccines.     

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh

Objectives

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content.

Methods

The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry.

Results

The median iAs concentration in drinking water was 55 μgAs/L (range <0.5–332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7–32.3), 1.8 (<0.5–3.3), 13.7 (5.6–25.0), and 88.6 μgAs/L (47.9–153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water.

Conclusions

All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.     

Saharan dust and associations between particulate matter and daily mortality in Rome, Italy

Background: Outbreaks of Saharan-Sahel dust over Euro-Mediterranean areas frequently induce exceedances of the Europen Union''s 24-hr standard of 50 μg/m³ for particulate matter (PM) with aerodynamic diameter ≤ than 10 μm (PM₁₀).Objectives: We evaluated the effect of Saharan dust on the association between different PM fractions and daily mortality in Rome, Italy.Methods: In a study of 80,423 adult residents who died in Rome between 2001 and 2004, we performed a time-series analysis to explore the effects of PM_2.5, PM_2.5–10, and PM₁₀ on natural, cardiac, cerebrovascular, and respiratory mortality. We defined Saharan dust days by combining light detection and ranging (LIDAR) observations and analyses from operational models. We tested a Saharan dust–PM interaction term to evaluate the hypothesis that the effects of PM, especially coarse PM (PM_2.5–10), on mortality would be enhanced on dust days.Results: Interquartile range increases in PM_2.5–10 (10.8 μg/m³) and PM₁₀ (19.8 μg/m³) were associated with increased mortality due to natural, cardiac, cerebrovascular, and respiratory causes, with estimated effects ranging from 2.64% to 12.65% [95% confidence interval (CI), 1.18–25.42%] for the association between PM_2.5–10 and respiratory mortality (0- to 5-day lag). Associations of PM_2.5–10 with cardiac mortality were stronger on Saharan dust days (9.73%; 95% CI, 4.25–15.49%) than on dust-free days (0.86%; 95% CI, –2.47% to 4.31%; p = 0.005). Saharan dust days also modified associations between PM₁₀ and cardiac mortality (9.55% increase; 95% CI, 3.81–15.61%; vs. dust-free days: 2.09%; 95% CI, –0.76% to 5.02%; p = 0.02).Conclusions: We found evidence of effects of PM_2.5–10 and PM₁₀ on natural and cause-specific mortality, with stronger estimated effects on cardiac mortality during Saharan dust outbreaks. Toxicological and biological effects of particles from desert sources need to be further investigated and taken into account in air quality standards.     

Profile of Presentation of Human Immunodeficiency Virus Infection in North India, 2003-2007

Background:

Clinico-epidemiological profile of the Human immunodeficiency virus (HIV) epidemic in India is varied and depends on multitude of factors including geographic location. We analyzed the characteristics of HIV-infected patients attending our Immunodeficiency Clinic to determine any changes in their profile over five years.

Settings and Design:

A retrospective observational study.

Materials and Methods:

The study sample included all patients with HIV infection from January 1, 2003 to December 31, 2007. Diagnosis of HIV was made according to National AIDS Control Organization guidelines.

Results:

Of 3 067 HIV-infected patients, 1 887 (61.5%) were male and 1 180 (38.5%) were female patients. Mean age of patients was 35.1 ± 9.0 years. Majority (91.8%) of patients were in the age group of 15 to 49 years. Progressively increasing proportion of female patients was noted from year 2004 onward. Median CD4 count at presentation in year 2003 was 197/μl (Interquartile range [IQR] = 82.5-373) while in year 2007 it was 186.5/μl (IQR = 86.3-336.8). Mean CD4 count of male patients was 203.7 ± 169.4/μl, significantly lower as compared with female patients, which was 284.8 ± 223.3/μl (P value ≤0.05). Every year, substantial proportions of patients presenting to clinic had CD4 count<200/μl indicating advanced disease. Predominant route of transmission was heterosexual in 2 507 (81.7%) patients. Tuberculosis and oropharyngeal candidiasis were the most common opportunistic infections (OIs). Cryptococcal meningitis was the most common central nervous infection. Our patients had comparatively lower median CD4 counts at the time of presentation with various OIs.

Conclusions:

Patients had advanced stage of HIV infection at the time of presentation throughout five years. Females presented earlier during the course of HIV infection. There is need for early screening and increasing awareness in healthcare providers to make a diagnosis of HIV much sooner.     

Effect of Dietary Fat Supplementation during Late Pregnancy and First Six Months of Lactation on Maternal and Infant Vitamin A Status in Rural Bangladesh

Dietary fat intake is extremely low in most communities with vitamin A deficiency. However, its role in vitamin A status of pregnant and lactating women is poorly understood. The aim of the study was to examine the effect of supplementing women with fat from mid-/late pregnancy until six months postpartum on their vitamin A status and that of their infants. Women recruited at 5-7 months of gestation were supplemented daily with 20 mL of soybean-oil (n=248) until six months postpartum or received no supplement (n=251). Dietary fat intake was assessed by 24-hour dietary recall at enrollment and at 1, 3 and 6 months postpartum. Concentrations of maternal plasma retinol, β-carotene, and lutein were measured at enrollment and at 1, 3 and 6 months postpartum, and those of infants at six months postpartum. Concentration of breastmilk retinol was measured at 1, 3 and 6 months postpartum. The change in concentration of plasma retinol at three months postpartum compared to pregnancy was significantly higher in the supplemented compared to the control women (+0.04 vs -0.07 μmol/L respectively; p<0.05). Concentrations of plasma β-carotene and lutein declined in both the groups during the postpartum period but the decline was significantly less in the supplemented than in the control women at one month (β-carotene -0.07 vs -0.13 μmol/L, p<0.05); lutein -0.26 vs -0.49 μmol/L, p<0.05) and three months (β-carotene -0.04 vs -0.08 μmol/L, p<0.05; lutein -0.31 vs -0.47 μmol/L, p<0.05). Concentration of breastmilk retinol was also significantly greater in the supplemented group at three months postpartum than in the controls (0.68±0.35 vs 0.55±0.34 μmol/L respectively, p<0.03). Concentrations of infants’ plasma retinol, β-carotene, and lutein, measured at six months of age, did not differ between the groups. Fat supplementation during pregnancy and lactation in women with a very low intake of dietary fat has beneficial effects on maternal postpartum vitamin A status.Key words: Community-based studies, Fat supplementation, Infant, Postpartum;Pregnancy, Vitamin A, Vitamin A deficiency, Bangladesh     

Lithium in drinking water and thyroid function

Background

High concentrations of lithium in drinking water were previously discovered in the Argentinean Andes Mountains. Lithium is used worldwide for treatment of bipolar disorder and treatment-resistant depression. One known side effect is altered thyroid function.

Objectives

We assessed associations between exposure to lithium from drinking water and other environmental sources and thyroid function.

Methods

Women (n = 202) were recruited in four Andean villages in northern Argentina. Lithium exposure was assessed based on concentrations in spot urine samples, measured by inductively coupled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T₄) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immunometric methods.

Results

The median urinary lithium concentration was 3,910 μg/L (5th, 95th percentiles, 270 μg/L, 10,400 μg/L). Median plasma concentrations (5th, 95th percentiles) of T₄ and TSH were 17 pmol/L (13 pmol/L, 21 pmol/L) and 1.9 mIU/L, (0.68 mIU/L, 4.9 mIU/L), respectively. Urine lithium was inversely associated with T₄ [β for a 1,000-μg/L increase = −0.19; 95% confidence interval (CI), −0.31 to −0.068; p = 0.002] and positively associated with TSH (β = 0.096; 95% CI, 0.033 to 0.16; p = 0.003). Both associations persisted after adjustment (for T₄, β = −0.17; 95% CI, −0.32 to −0.015; p = 0.032; for TSH: β = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). Urine selenium was positively associated with T₄ (adjusted T₄ for a 1 μg/L increase: β = 0.041; 95% CI, 0.012 to 0.071; p = 0.006).

Conclusions

Exposure to lithium via drinking water and other environmental sources may affect thyroid function, consistent with known side effects of medical treatment with lithium. This stresses the need to screen for lithium in all drinking water sources.     

The Prevalence and Risk Factors Associated with Iodine Deficiency in Canadian Adults

Iodine is a trace micronutrient that is critical for normal thyroid function and human health. Inadequate dietary intake is associated with cognitive impairment, infertility, growth retardation and iodine deficiency disorders in affected populations. Herein, we examined the prevalence of iodine deficiency in adults (median age of 61 years) based on the analysis of 24 h urine samples collected from 800 participants in four clinical sites across Canada in the Prospective Urban and Rural Epidemiological (PURE) study. Urinary iodide together with thiocyanate and nitrate were measured using a validated capillary electrophoresis assay. Protective/risk factors associated with iodine deficiency were identified using a binary logistic regression model, whereas daily urinary iodine concentration (24 h UIC, μg/L) and urinary iodine excretion (24 h UIE, μg/day) were compared using complementary statistical methods with covariate adjustments. Overall, our Canadian adult cohort had adequate iodine status as reflected by a median UIC of 111 μg/L with 11.9% of the population <50 μg/L categorized as having moderate to severe iodine deficiency. Iodine adequacy was also evident with a median 24 h UIE of 226 μg/day as a more robust metric of iodine status with an estimated average requirement (EAR) of 7.1% (< 95 μg/day) and a tolerable upper level (UL) of 1.8% (≥1100 μg/day) based on Canadian dietary reference intake values. Participants taking iodine supplements (OR = 0.18; p = 6.35 × 10⁻⁵), had greater 24 h urine volume (OR = 0.69; p = 4.07 × 10⁻⁴), excreted higher daily urinary sodium (OR = 0.71; p = 3.03 × 10⁻⁵), and/or were prescribed thyroxine (OR = 0.33; p = 1.20 × 10⁻²) had lower risk for iodine deficiency. Self-reported intake of dairy products was most strongly associated with iodine status (r = 0.24; p = 2.38 × 10⁻⁹) after excluding for iodine supplementation and T4 use. Participants residing in Quebec City (OR = 2.58; p = 1.74 × 10⁻⁴) and Vancouver (OR = 2.54; p = 3.57 × 10⁻⁴) were more susceptible to iodine deficiency than Hamilton or Ottawa. Also, greater exposure to abundant iodine uptake inhibitors from tobacco smoking and intake of specific goitrogenic foods corresponded to elevated urinary thiocyanate and nitrate, which were found for residents from Quebec City as compared to other clinical sites. Recent public health policies that advocate for salt restriction and lower dairy intake may inadvertently reduce iodine nutrition of Canadians, and further exacerbate regional variations in iodine deficiency risk.     

An investigation of modifying effects of metallothionein single-nucleotide polymorphisms on the association between mercury exposure and biomarker levels

Background: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans.Objective: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure–biomarker relationships.Methods: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methylmercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated.Results: The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the U.S. general population (0.95 μg/L and 0.47 μg/g, respectively). The mean estimated daily MeHg intake was 0.084 μg/kg/day (range, 0–0.98 μg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 μg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270837) AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1M TC and CC genotypes (n = 15), respectively.Conclusion: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general population.     

Associations of early childhood manganese and lead coexposure with neurodevelopment

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.     

Effect of micronutrient and probiotic fortified yogurt on immune-function of anti-retroviral therapy naive HIV patients

Background: Micronutrient supplementation has been shown to reduce the progression of HIV but does not have an effect on the intestinal barrier or the intestinal microbiota of HIV patients. Studies have suggested that probiotics could potentially complement micronutrients in preserving the immune-function of HIV patients. Objective: Assess the impact of micronutrient supplemented probiotic yogurt on the immune function of HIV patients. Design:We performed a randomized, double blind, controlled trial with CD4 count as primary outcome among HIV patients naïve to anti-retroviral treatment. Secondary outcomes included hematological parameters, incidence of diarrhea and clinical symptoms. A total of 112 HIV patients were randomized to receive a micronutrient fortified yogurt with (n = 55) or without additional probiotic Lactobacillus rhamnosus GR-1 (n = 57) for four weeks. Results:An average decline in CD4 count of −70 cells/μL (95% CI: −154 to −15) was observed in the micronutrient, probiotic group versus a decrease of −63 cells/μL (95% CI: −157 to −30) in the micronutrient control group (p = 0.9). Additional probiotic supplementation was well tolerated and not associated with adverse events. No difference between groups was detected in incidence of diarrhea or clinical symptoms. An improvement of hemoglobin levels was observed for all subjects, based upon a mean difference from baseline of 1.4 g/L (SD = 6) (p = 0.02). Conclusion:The addition of probiotics to a micronutrient fortified yogurt was well tolerated by HIV patients but was not associated with a further increase in CD4 count after one month.     

天津市城市地区3～6岁儿童血尿酸水平及正常参考值范围探讨分析

目的了解天津市城市地区3~6岁儿童血尿酸水平及分布特征,探讨其正常参考值范围。方法随机抽取天津市城市地区26所幼儿园4 083名3~6岁儿童,采集末梢血,检测血浆尿酸水平。结果 1)血尿酸水平为(243.0±52.8)μmol/L,男童尿酸水平高于女童(t=5.423,P0.001);5~6岁组高于3~4岁组(t=-2.245,P=0.025);肥胖组儿童血尿酸水平高于超重组及体型正常组(F=58.641,P0.001)。2)选择体型正常和超重儿童为"健康人群",根据不同年龄、性别分别计算尿酸正常值,3~4岁组男童(240.8±101.1)μmol/L,女童(235.2±105.8)μmol/L,5~6岁组男童(244.1±101.4)μmol/L,女童(236.5±98.6)μmol/L。结论性别、年龄、体型是影响城市地区3~6岁儿童尿酸水平的重要因素。根据不同性别及年龄建立的城市地区3~6岁儿童血尿酸水平弥补了当前缺乏相应标准的不足。     

Maternal Blood,Plasma, and Breast Milk Lead: Lactational Transfer and Contribution to Infant Exposure

Background: Human milk is a potential source of lead exposure. Yet lactational transfer of lead from maternal blood into breast milk and its contribution to infant lead burden remains poorly understood.Objectives: We explored the dose–response relationships between maternal blood, plasma, and breast milk to better understand lactational transfer of lead from blood and plasma into milk and, ultimately, to the breastfeeding infant.Methods: We measured lead in 81 maternal blood, plasma, and breast milk samples at 1 month postpartum and in 60 infant blood samples at 3 months of age. Milk-to-plasma (M/P) lead ratios were calculated. Multivariate linear, piecewise, and generalized additive models were used to examine dose–response relationships between blood, plasma, and milk lead levels.Results: Maternal lead levels (mean ± SD) were as follows: blood: 7.7 ± 4.0 μg/dL; plasma: 0.1 ± 0.1 μg/L; milk: 0.8 ± 0.7 μg/L. The average M/P lead ratio was 7.7 (range, 0.6–39.8) with 97% of the ratios being > 1. The dose–response relationship between plasma lead and M/P ratio was nonlinear (empirical distribution function = 6.5, p = 0.0006) with the M/P ratio decreasing by 16.6 and 0.6 per 0.1 μg/L of plasma lead, respectively, below and above 0.1 μg/L plasma lead. Infant blood lead level (3.4 ± 2.2 μg/dL) increased by 1.8 μg/dL per 1 μg/L milk lead (p < 0.0001, R² = 0.3).Conclusions: The M/P ratio for lead in humans is substantially higher than previously reported, and transfer of lead from plasma to milk may be higher at lower levels of plasma lead. Breast milk is an important determinant of lead burden among breastfeeding infants.Citation: Ettinger AS, Roy A, Amarasiriwardena CJ, Smith DR, Lupoli N, Mercado-García A, Lamadrid-Figueroa H, Tellez-Rojo MM, Hu H, Hernández-Avila M. 2014. Maternal blood, plasma, and breast milk lead: lactational transfer and contribution to infant exposure. Environ Health Perspect 122:87–92; http://dx.doi.org/10.1289/ehp.1307187     

Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment

Objectives

To clarify the causes of death of residents with renal tubular dysfunction induced by cadmium (Cd) in the environment.

Methods

A 15 year follow up study was performed with the inhabitants living in the Cd polluted Kakehashi River basin in Japan. Standardised mortality ratios (SMRs) for causes of death, classified by ICD‐9, were computed using the person‐years method to investigate the excess mortality of subjects with urinary β2‐MG (microglobulin) ⩾1000 μg/gCr. Mortality risk analysis was performed using Cox''s proportional model to compare mortality between subjects with urinary β2‐MG ⩾1000 and <1000 μg/gCr, and to investigate the relationship between the degree of urinary β2‐MG and mortality.

Results

Excess mortality due to heart failure and cerebral infarction in both sexes, and nephritis and nephrosis in men, was observed among subjects with urinary β2‐MG ⩾1000 μg/gCr. Significant increases in mortality risk for cerebral infarction in men and for malignant neoplasms in women with urinary β2‐MG ⩾1000 μg/gCr were observed during the first five year observation period. For nephritis and nephrosis, the mortality risks for men and women with urinary β2‐MG ⩾1000 μg/gCr significantly increased over the 15 year observation period. The mortality risks for heart failure and cerebral infarction increased in proportion to the increased urinary β2‐MG in both sexes. Increased mortality risks for nephritis and nephrosis were identified in the subjects with urinary β2‐MG ⩾10000 μg/gCr in both sexes.

Conclusion

Renal tubular dysfunction induced by Cd affected the causes of death, and mortality for heart failure, cerebral infarction, and nephritis and nephrosis was increased among inhabitants living in a Cd polluted area in Japan. In women, cancer mortality may have been increased while Cd pollution was ongoing.     

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming.Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure.Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1–230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation.Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.     

P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease, is associated with blood pressure

Background

Moyamoya disease—an idiopathic vascular disorder of intracranial arteries—is often accompanied by hypertension. RNF213 has been identified as a susceptibility gene for moyamoya disease. In the present study, the association of p.R4810K (G>A) with blood pressure (BP) was investigated in a Japanese population.

Methodology/principal findings

Three independent study populations, the Nyukawa (n = 984), Noshiro (n = 2,443) and Field (n = 881) studies, joined this study. BP, body weight and height were measured. Past and present symptoms and disease and medication histories were assessed by interview. Associations of p.R4810K (rs112735431, ss179362673) of RNF213 with BP were investigated. Two linkage disequilibrium blocks were constructed for moyamoya patients with p.R4810K (n = 140) and the general population (n = 384) using 39 single nucleotide polymorphisms (SNPs) spanning 390 kb around RNF213. A total of 60 carriers (3 for AA genotype and 57 for GA genotype) were found in these samples, and the minor allele frequencies were 1.4 % in the Nyukawa and Field studies and 0.2 % in the Noshiro study. Regression analyses adjusted for age, sex and body mass index based on an additive model demonstrated significant associations with systolic BP (mmHg/allele): β (standard error) was 8.2 (2.9) in the Nyukawa study (P = 4.7 × 10⁻³), 18.7 (5.4) in the Noshiro study (P = 4.6 × 10⁻⁴) and 8.9 (2.0) (P = 1.0 × 10⁻⁵) in the three populations. In contrast, diastolic BP showed significant associations only in the Noshiro study. Linkage disequilibrium blocks contained none of the BP-associated proxy SNPs reported by previous studies.

Conclusions/significance

Our study suggests that p.R4810K of RNF213 is associated strongly with systolic BP.

Electronic supplementary material

The online version of this article (doi:10.1007/s12199-012-0299-1) contains supplementary material, which is available to authorized users.     

Biomarkers of methylmercury exposure immunotoxicity among fish consumers in Amazonian Brazil

Background: Mercury (Hg) is a ubiquitous environmental contaminant with neurodevelopmental and immune system effects. An informative biomarker of Hg-induced immunotoxicity could aid studies on the potential contribution to immune-related health effects.Objectives: Our objectives were to test the hypothesis that methylmercury (MeHg) exposures affect levels of serum biomarkers and to examine interactions between Hg and selenium (Se) in terms of these responses.Methods: This cross-sectional epidemiological study assessed adults living along the Tapajós River, a system long affected by MeHg. We measured antinuclear (ANA) and antinucleolar (ANoA) autoantibody levels and eight cytokines in serum samples (n = 232). Total Hg (including MeHg) and Se were measured in blood, plasma, hair, and urine.Results: The median (range) total Hg concentrations were 14.1 μg/g (1.1–62.4), 53.5 μg/L (4.3–288.9), 8.8 μg/L (0.2–40), and 3.0 μg/L (0.2–16.1) for hair, blood, plasma, and urine, respectively. Elevated titers of ANA (but not ANoA) were positively associated with MeHg exposure (log-transformed, for blood and plasma), unadjusted [odds ratio (OR) = 2.6; 95% confidence interval (CI): 1.1, 6.2] and adjusted for sex and age (OR = 2.9; 95% CI: 1.1, 7.5). Proinflammatory [interleukin (IL)-6 and interferon (IFN)-©], anti-inflammatory (IL-4), and IL-17 cytokine levels were increased with MeHg exposure; however, in the subset of the population with elevated ANA, proinflammatory IL-1®, IL-6, IFN-©, and tumor necrosis factor (TNF)-〈 and anti-inflammatory (IL-4) cytokine levels were decreased with MeHg exposure. Although Se status was associated with MeHg level (correlation coefficient = 0.86; 95% CI: 0.29, 1.43), Se status was not associated with any changes in ANA and did not modify associations between Hg and ANA titers.Conclusions: MeHg exposure was associated with an increased ANA and changes in serum cytokine profile. Moreover, alterations in serum cytokine profiles differed based on ANA response, suggesting a specific phenotype of MeHg susceptibility. Further research on the potential health implications of these observed immunological changes is warranted.     

Reducing personal exposure to particulate air pollution improves cardiovascular health in patients with coronary heart disease

Background: Air pollution exposure increases cardiovascular morbidity and mortality and is a major global public health concern.Objectives: We investigated the benefits of reducing personal exposure to urban air pollution in patients with coronary heart disease.Methods: In an open randomized crossover trial, 98 patients with coronary heart disease walked on a predefined route in central Beijing, China, under different conditions: once while using a highly efficient face mask, and once while not using the mask. Symptoms, exercise, personal air pollution exposure, blood pressure, heart rate, and 12-lead electrocardiography were monitored throughout the 24-hr study period.Results: Ambient air pollutants were dominated by fine and ultrafine particulate matter (PM) that was present at high levels [74 μg/m³ for PM_2.5 (PM with aerodynamic diamater <2.5 µm)]. Consistent with traffic-derived sources, this PM contained organic carbon and polycyclic aromatic hydrocarbons and was highly oxidizing, generating large amounts of free radicals. The face mask was well tolerated, and its use was associated with decreased self-reported symptoms and reduced maximal ST segment depression (–142 vs. –156 μV, p = 0.046) over the 24-hr period. When the face mask was used during the prescribed walk, mean arterial pressure was lower (93 ± 10 vs. 96 ± 10 mmHg, p = 0.025) and heart rate variability increased (high-frequency power: 54 vs. 40 msec², p = 0.005; high-frequency normalized power: 23.5 vs. 20.5 msec, p = 0.001; root mean square successive differences: 16.7 vs. 14.8 msec, p = 0.007). However, mask use did not appear to influence heart rate or energy expenditure.Conclusions: Reducing personal exposure to air pollution using a highly efficient face mask appeared to reduce symptoms and improve a range of cardiovascular health measures in patients with coronary heart disease. Such interventions to reduce personal exposure to PM air pollution have the potential to reduce the incidence of cardiovascular events in this highly susceptible population.     

三手烟对小鼠内皮祖细胞水平的影响及可能机制

目的探讨三手烟对小鼠内皮祖细胞水平的影响及可能机制.方法 40只8周龄清洁级雄性小鼠,分为3组并做如下处理:对照组(n=10):暴露于正常空气中;一手烟组(n=15):每日接受香烟烟雾8小时;三手烟组(n=15):每日生活在香烟烟雾熏过的无菌敷料中8小时(无菌敷料接受同一手烟组一样的香烟烟雾烟熏8小时).两个月后采血,测定并比较两组内皮祖细胞(endothelial progenitor cells ,EPCs),髓过氧化物酶(myeloperoxidase ,MPO),白细胞介素-6(interleukin -6 ,IL-6),肿瘤坏死因子-α(tumor necrosis factor -α,TNF-α),一氧化氮(nitric oxide ,NO)水平.光镜下观察比较心肌组织学变化.结果 一手烟组,三手烟组与对照组相比,EPCs百分比显著下降[分别 (0.045±0.029)% vs (0.099±0.023) %,(0.047±0.023)% vs (0.099±0.023) %,均P<0.001),MPO, IL-6,TNF-α水平显著升高[分别为MPO: 1.39±0.26) U/g vs (0.48±0.17) U/g,(1.35±0.32) U/g vs (0.48±0.17) U/g;IL-6:(3.83±0.13) ng/ml vs (0.79±0.12) ng/ml,(3.45±0.15) ng/ml vs (0.79±0.12) ng/ml;TNF-α:(1.77±0.26) ng/ml vs (0.81±0.21) ng/ml,(1.78±0.23) ng/ml vs (0.81±0.21) ng/ml, 均P<0.001),NO水平显著降低[分别为(0.057±0.0063) μmol/L vs (0.080±0.0067) μmol/L,(0.060±0.0072) μmol/L vs (0.080±0.0067) μmol/L,均P<0.001);一手烟组,三手烟组比较各指标差异无统计学意义(均P>0.05),光镜下可见观察一手烟组,三手烟组与对照组相比心肌组织发生明显损伤.结论 三手烟可通过氧化应激和炎症反应降低小鼠内皮祖细胞水平,损伤小鼠心肌组织,作用程度与一手烟相似.