Orbital complications of paranasal sinusitis in Taiwan, 1988 through 2015: Acute ophthalmological manifestations, diagnosis, and management.

PURPOSE: Paranasal sinusitis is widespread and can lead to orbital complications, blindness, and death. However, the correlation between ophthalmological findings and disease staging remains unclear. This study aimed to investigate the staging, acute ophthalmological manifestations, diagnosis, management, and outcomes of orbital complications of paranasal sinusitis during a 27-year period. METHODS: We retrospectively reviewed the medical records of all patients with orbital complications of paranasal sinusitis hospitalized at the National Cheng Kung University Hospital, a medical center in Taiwan during 1988-2015. Sex, age, symptoms, history, ophthalmological findings, laboratory and imaging findings, treatments, and outcomes were analyzed by staging. RESULTS: Eighty-three patients aged 9 days to 80 years had stage I (preseptal cellulitis, n = 39 patients), II (postseptal orbital cellulitis, n = 8), III (subperiosteal abscess, n = 16), IV (orbital abscess, n = 8), or V (intracranial involvement, n = 12) complications. Peak incidences occurred in patients aged 0-19 and 60-69 years. Chronic sinusitis and diabetes mellitus were common preexisting diseases. Extraocular movement limitation and proptosis predicted postseptal (stage II or more) involvement. The likelihood of elevated intraocular pressure increased with stage. Reduced visual acuity and presence of relative afferent pupillary defect indicated consideration of magnetic resonance imaging to investigate possible intracranial extension. Ipsilateral maxillary (81.7%) and ethmoidal (75.6%) sinuses were the most common sources of infection, and the most frequently implicated pathogens were coagulase-negative Staphylococcus spp. (25.3%) and Staphylococcus aureus (20.5%). All patients received intravenous antimicrobial therapy (multi-drug therapy in 88.0%), and 55.4% underwent surgery, most commonly endoscopic sinus surgery. One (1.2%) diabetic man with stage V complications died of fungal sinusitis with intracranial invasion. Five (6.0%) patients, all stage V, lost vision despite intensive treatment. The average length of hospital stay was 13.8 days (range 2-72 days), and significantly longer stays were associated with stages II-V as compared to stage I. CONCLUSIONS: Orbital infection originating from paranasal sinusitis can cause vision loss and death due to intracranial extension. Acute ophthalmological findings predict staging and prognosis. Cooperative consultation between ophthalmologists, otorhinolaryngologists, and neurologists is essential. Urgent diagnostic studies and aggressive antimicrobial therapy are indicated, and surgery should be considered.

Prenatal and childhood exposure to phthalate diesters and sex steroid hormones in 2-, 5-, 8-, and 11-year-old children: A pilot study of the Taiwan Maternal and Infant Cohort Study.

BACKGROUND: Phthalate diesters are commonly used and have been well established as environmental endocrine disruptors. However, few studies have examined their effects on sex steroid hormones in children. We followed children over time to examine the association between pre- and post-natal phthalate exposure and sex steroid hormone levels at 2, 5, 8, and 11 years of age. METHODS: We recruited 430 pregnant women from central Taiwan from 2000 to 2001 and assessed their children at birth, 2, 5, 8, and 11 years of age. We studies children with at least one measurement for both phthalate and hormone levels during each any of the follow-up time point (n = 193). Estradiol, free testosterone, testosterone, and progesterone were measured from venous blood. Three monoesters of di-2-ethylhexyl phthalate (DEHP), mono-benzyl phthalate, mono-n-butyl phthalate, mono-ethyl phthalate, and mono-methyl phthalate were measured in maternal urine collected during the 3rd trimester and child urine collected at each follow-up point. The sum of mono-2-ethylhexyl phthalate (∑MEHP) was calculated by summing the concentrations of the three DEHP monoesters. Generalized estimating equation regression analysis with repeated measures was used to estimate associations between phthalate metabolites and hormone levels. RESULTS: After adjustment for potential confounders, maternal ∑MEHP level was associated with decreased levels of progesterone in girls (ß = -0.309 p = 0.001). The child ∑MEHP concentration was associated with decreased levels of progesterone for girls (ß = -0.194, p = 0.003) and with decreased levels of free testosterone for boys (ß = -0.124, p = 0.004). CONCLUSIONS: Early-life DEHP exposure may alter sex steroid hormones of children over time, which may pose potential reproductive health risks.

Prenatal Exposure to Perfluorocarboxylic Acids (PFCAs) and Fetal and Postnatal Growth in the Taiwan Maternal and Infant Cohort Study.

BACKGROUND: Perfluorocarboxylic acids (PFCAs) are environmentally and biologically persistent synthetic chemicals. PFCAs include perfluorooctanoic acid (PFOA; C8) and long-chain PFCAs (C9-C20). Studies examining long-chain PFCAs and fetal and postnatal growth are limited. OBJECTIVES: We investigated the associations of prenatal exposure to long-chain PFCAs with fetal and postnatal growth. METHODS: For 223 Taiwanese mothers and their term infants, we measured PFOA and four long-chain PFCAs (ng/mL) in third-trimester maternal serum; infant weight (kg), length and head circumference (cm) at birth; and childhood weight and height at approximately 2, 5, 8, and 11 years of age. For each sex, we used multivariable linear regression to examine associations between ln-transformed prenatal PFCAs and continuous infant measures, and logistic regression to examine small for gestational age (SGA). Linear mixed models were applied to prenatal PFCAs and childhood weight and height z-scores. RESULTS: In girls, prenatal perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) concentrations were inversely associated with birth weight [e.g., ßbirth weight (kg) = -0.06, 95% CI: -0.11, -0.01 per 1 ln-unit PFUnDA increase]; prenatal PFDeA and PFUnDA were associated with elevated odds of SGA; and PFDeA, PFUnDA, and PFDoDA were associated with lower average childhood height z-score. In boys, prenatal PFNA, and PFDoDA were associated with reductions in height at certain ages in childhood, but not with size at birth. CONCLUSIONS: Prenatal exposure to long-chain PFCAs may interfere with fetal and childhood growth in girls, and childhood growth in boys. Citation: Wang Y, Adgent M, Su PH, Chen HY, Chen PC, Hsiung CA, Wang SL. 2016. Prenatal exposure to perfluorocarboxylic acids (PFCAs) and fetal and postnatal growth in the Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 124:1794-1800; http://dx.doi.org/10.1289/ehp.1509998.

Prenatal exposure to perfluroalkyl substances and children's IQ: The Taiwan maternal and infant cohort study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a group of fluorinated organic substances that are widely used in consumer products and are often detectable in human tissues. Human studies on prenatal exposure to PFASs and neurodevelopment in children are few and inconsistent. METHODS: In the Taiwan Maternal and Infant Cohort Study, we collected serum samples from pregnant women during the third trimester and measured concentrations of 9 PFASs using a high performance liquid chromatography system. A subsample of their children was assessed with full scale intelligence quotient (FSIQ), verbal IQ (VIQ) and performance IQ (PIQ) at both age 5 (n=120) and 8 years (n=120). We used multivariate linear regression models to examine prenatal PFAS exposure in relation to IQ scores at each age period. RESULTS: Prenatal perfluoroundecanoic acid (PFUnDA) concentrations were inversely associated with children's PIQ scores at age 5 years, with an adjusted coefficient (ß) of -1.6 (95% confidence interval [CI]: (-3.0, -0.2). When children reached 8 years, most of the prenatal PFASs showed inverse association with children's FSIQ, VIQ and PIQ scores. Among them, prenatal perfluorononanoic acid (PFNA) reached significance. Children with higher prenatal PFNA levels had lower VIQ with an adjusted ß of -2.1 (95% CI: -3.9, -0.2). CONCLUSIONS: We found two prenatal PFAS exposure, both long-chain PFASs, in association with decreased IQ test scores in children. Our findings suggest more studies on long-chain PFASs and children's neurodevelopment.

Fetal and Childhood Exposure to Phthalate Diesters and Cognitive Function in Children Up to 12 Years of Age: Taiwanese Maternal and Infant Cohort Study.

Few studies have examined the association between environmental phthalate exposure and children's neurocognitive development. This longitudinal study examined cognitive function in relation to pre-and postnatal phthalate exposure in children 2-12 years old. We recruited 430 pregnant women in their third trimester in Taichung, Taiwan from 2001-2002. A total of 110, 79, 76, and 73 children were followed up at ages 2, 5, 8, and 11, respectively. We evaluated the children's cognitive function at four different time points using the Bayley and Wechsler tests for assessing neurocognitive functions and intelligence (IQ). Urine samples were collected from mothers during pregnancy and from children at each follow-up visit. They were analyzed for seven metabolite concentrations of widely used phthalate esters. These esters included monomethyl phthalate, monoethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, and three metabolites of di(2-ethylhexyl) phthalate, namely, mono-2-ethylhexyl phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. We constructed a linear mixed model to examine the relationships between the phthalate metabolite concentrations and the Bayley and IQ scores. We found significant inverse associations between the children's levels of urinary mono(2-ethyl-5-oxohexyl) phthalate and the sum of the three metabolites of di(2-ethylhexyl) phthalate and their IQ scores (ß = -1.818; 95% CI: -3.061, -0.574, p = 0.004 for mono(2-ethyl-5-oxohexyl) phthalate; ß = -1.575; 95% CI: -3.037, -0.113, p = 0.035 for the sum of the three metabolites) after controlling for maternal phthalate levels and potential confounders. We did not observe significant associations between maternal phthalate exposure and the children's IQ scores. Children's but not prenatal phthalate exposure was associated with decreased cognitive development in the young children. Large-scale prospective cohort studies are needed to confirm these findings in the future.

Thyroid and growth hormone concentrations in 8-year-old children exposed in utero to dioxins and polychlorinated biphenyls.

The objective of this study was to examine the effects of in utero exposure to polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/F) on thyroid and growth hormone concentrations and growth in 8-year-old children. A total of 56 children (23 boys, 33 girls) were included in the study. All were stratified into high and low PCDD/F + PCB exposure groups based on maternal median indicator PCB and PCDD/F + PCB concentrations during pregnancy. Height, weight, body mass index, and thyroid and growth hormone concentrations were assessed and compared among the different exposure groups. There were no significant effects of indicator PCB or PCDD/F + PCB exposure levels on growth (height, weight, and bone age) among 8-year-old boys or girls. Boys exposed to high PCDD/F + PCB levels had significantly higher thyroxine-binding globulin (TBG) concentrations than boys exposed to low levels (P = 0.027). Girls exposed to high PCB levels had significantly lower IGF-binding protein-3 (IGFBP-3) concentrations than girls exposed to low levels (P = 0.038). Low levels of in utero exposure to PCDD/F+PCB and high indicator PCB levels were significantly associated with reduced serum concentrations of IGFBP-3. High levels of in utero exposure to PCDD/F+PCB plus either high or low indicator PCB levels were significantly associated with increased serum concentrations of growth hormone, T3, T4, and TBG. These findings suggest that the level of in utero exposure to PCBs and dioxins may affect serum concentrations of growth hormone, thyroid hormones, TBG, and IGFBP-3 in 8-year-old children.

Prenatal and postnatal exposure to phthalate esters and asthma: a 9-year follow-up study of a taiwanese birth cohort.

Previous studies have shown that phthalate exposure in childhood is associated with the development of respiratory problems. However, few studies have assessed the relative impact of prenatal and postnatal exposure to phthalates on the development of asthma later in childhood. Therefore, we assessed the impact of prenatal and postnatal phthalate exposure on the development of asthma and wheezing using a Taiwanese birth cohort. A total of 430 pregnant women were recruited, and 171 (39.8%) of them had their children followed when they were aged 2, 5, and 8 years. The International Study of Asthma and Allergies in Childhood questionnaire was used to assess asthma and wheezing symptoms and serum total immunoglobulin E levels were measured at 8 years of age. Urine samples were obtained from 136 women during their third trimester of pregnancy, 99 children at 2 years of age, and 110 children at 5 years. Four common phthalate monoester metabolites in maternal and children's urine were measured using liquid chromatography-electrospray ionization-tandem mass spectrometry. Maternal urinary mono-benzyl phthalate [MBzP] concentrations were associated with an increased occurrence of wheezing in boys at 8 years of age (odds ratio [OR] = 4.95 (95% CI 1.08-22.63)), for upper quintile compared to the others) after controlling for parental allergies and family members' smoking status. Urinary mono-2-ethylhexyl phthalate [MEHP] levels over the quintile at 2-year-old were associated with increased asthma occurrence (adjusted OR = 6.14 (1.17-32.13)) in boys. Similarly, the sum of di-2-ethyl-hexyl phthalate [DEHP] metabolites at 5 years was associated with asthma in boys (adjusted OR = 4.36 (1.01-18.86)). Urinary MEHP in maternal and 5-year-old children urine were significantly associated with increased IgE in allergic children at 8 years. Prenatal and postnatal exposure to phthalate was associated with the occurrence of asthma in children, particularly for boys.

Prenatal exposure to phthalate esters and behavioral syndromes in children at 8 years of age: Taiwan Maternal and Infant Cohort Study.

BACKGROUND: Few studies have shown an association between prenatal phthalate exposure and adverse effects on neurodevelopment and behavior in young children. OBJECTIVES: We aimed to assess the relationship between prenatal exposure to phthalate esters and behavior syndromes in children at 8 years of age. METHODS: A total of 122 mother-child pairs from the general population in central Taiwan were studied from 2000 to 2009. Mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and three di-(2-ethylhexyl) phthalate (DEHP) metabolites-mono-2-ethylhexyl, mono-2-ethyl-5-hydroxyhexyl, and mono-2-ethyl-5-oxohexyl phthalates (MEHP, MEHHP, and MEOHP)--were measured in maternal urine collected during the third trimester of pregnancy using liquid chromatography-electrospray ionization-tandem mass spectrometry. Behavioral syndromes of children at 8 years of age were evaluated using the Child Behavior Checklist (CBCL). Associations between log10-transformed creatinine-corrected phthalate concentrations and standardized scores of the CBCL were estimated using linear regression models or multinomial logistic regressions with adjustments for potential confounders. RESULTS: Externalizing problem scores were significantly higher in association with a 1-unit increase in log10-transformed creatinine-corrected concentrations of maternal MBP (ß = 4.29; 95% CI: 0.59, 7.99), MEOHP (ß = 3.74; 95% CI: 1.33, 6.15), and MEHP (ß = 4.28 ; 95% CI: 0.03, 8.26) after adjusting for the child's sex, intelligence, and family income. Meanwhile, MBP and MEOHP were significantly associated with Delinquent Behavior and Aggressive Behavior scores. The same pattern was found for borderline and/or clinical ranges. CONCLUSIONS: Our findings suggest positive associations between maternal DEHP and dibutyl phthalate (DBP) exposure and externalizing domain behavior problems in 8-year-old children.

Prenatal exposure to phthalate ester and pubertal development in a birth cohort in central Taiwan: a 12-year follow-up study.

Phthalate esters are widely used plasticizers that are present in many daily used products. Although some of their reproductive effects have been reported, pubertal development effects from prenatal exposure to phthalates awaits further investigations. A population based birth cohort was established (N=437 at baseline) with maternal exposure to phthalates assessed in urine collected at the third trimester of pregnancy in 2001 and 2002. Their 133 children with prenatal phthalates exposure were followed up for the outcomes of pubertal development by sequential physical examinations at eight and 11 years old in 2009 and 2012. Urinary concentrations of major phthalate metabolites (i.e., mono-2-ethylhexyl phthalate [MEHP], mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP], mono-(2-ethyl-5-oxohexyl) phthalate [MEOHP], mono-butyl phthalate [MBP], mono-benzyl phthalate [MBzP], monomethyl phthalate [MMP], and mono-ethyl phthalate [MEP]) were determined using liquid chromatography linked to tandem mass spectrometry. The reproductive development measurements included bone age (for both genders), testicle size (for boys), uterus size, and ovarian volume (for girls). We reported results of 133 children with complete data by applying generalized estimating equations for the repeated continuous outcomes. After controlling for Tanner stage, we detected a significant association between reduced uterus size and increasing phthalate exposure in the 2(nd) tertile relative to the 1st tertile of creatinine-corrected MEHP (B=-0.40; 95% C.I.: -0.73, -0.07, relative to the 1st tertile) and total DEHP (B=-0.39, 95% C.I.:-0.66, -0.01 for the 2nd tertile and B=0.34, 95% C.I.: -0.67, -0.01 for the 3rd tertile, relative to the 1st tertile) with a linear trend among girls. MBzP was also found negatively associated with bone age/chronological age ratio (B=-0.07, 95% CI: -0.13, -0.01 for the 3rd tertile, relative to the 1st tertile) with a linear trend for girls. We found no evidence of an association between phthalate exposure and ovarian volume or testicle size. This analysis suggests phthalate exposure may affect specific pubertal development characteristics in human beings. Further studies with larger sample sizes and longer follow-up period are warranted.

Sex steroid hormone levels and reproductive development of eight-year-old children following in utero and environmental exposure to phthalates.

In utero exposure to phthalates may adversely affect reproductive development in children due to the anti-androgenic properties of the pthalates. Accordingly, we aimed to determine the effects of in utero and environmental phthalate exposure on the reproductive development of eight-year-old children. We recruited 180 children in central Taiwan during November 2001 and followed them until August 2009 when all children became eight years old. Birth outcomes were collected. Bone age, hormone concentrations, and reproductive developmental stages were determined. Phthalate metabolite levels, including mono-2-ethylhexyl phthalate [MEHP], mono-n-butyl phthalate [MnBP], and mono-benzyl phthalate [MBzP], were assessed. No significant gender differences were found in in utero phthalate exposure. Maternal urinary levels of phthalate metabolites did not correlate significantly with birth outcomes, physical characteristics, and reproductive hormones of the eight-year-old children. Regarding the urinary phthalate metabolite levels of the eight-year-old children, MEHP correlated significantly with serum progesterone levels. MEHP levels in girls correlated significantly with serum progesterone levels. MnBP correlated significantly with serum FSH in all children. In girls, MnBP correlated with serum FSH, and MBzP correlated with serum progesterone and FSH levels. Urinary phthalate metabolite levels did not correlate with female developmental stages or the development of female reproductive organs. Phthalate metabolites did not correlate with the physical characteristics and reproductive hormones in boys. Therefore, environmental exposure to phthalates, as determined by urinary phthalate metabolite levels of eight-year-old children, may affect reproductive hormone levels in children, indicating that further studies on the environmental health effects of phthalates are warranted.

Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan maternal and infant cohort study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment. OBJECTIVES: We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates. METHODS: In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models. RESULTS: Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T4) and total T4 levels. For example, we estimated that maternal free T4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T3. CONCLUSIONS: Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses.

Maternal arsenic exposure and DNA damage biomarkers, and the associations with birth outcomes in a general population from Taiwan.

Inorganic arsenic (iAs) is an established transplacental agent known to affect fetal development in animal studies. However, iAs has not been adequately studied in the general population with respect to iAs exposure during pregnancy and its impact on the health status of newborns. The aims of this study were to 1) elucidate the association between arsenic exposure and oxidative/methylated DNA damage in pregnant women, and 2) determine the association with birth outcomes. A birth cohort study of 299 pregnant mother-newborn pairs was recruited during 2001-2002 in Taiwan. We collected maternal urine samples during the 3(rd) trimester for measuring iAs and its metabolites. We used high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for quantifications of the arsenic species. Liquid chromatography/tandem mass spectrometer (LC-MS/MS) was used to measure the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and N(7)-methylguanosine (N(7)-MeG) DNA damage biomarkers. Birth outcomes were collected to assess the associations with maternal arsenic exposure and the DNA damage biomarkers. Multiple regression analyses showed that maternal urinary iAs had positive associations with the methylated N(7)-MeG (beta = 0.35, p<0.001) and oxidative 8-oxodG (beta = 0.24, p<0.001) DNA damage biomarkers, and a decreased one-minute (1-min) Apgar score (beta = -0.23, p = 0.041). Maternal N(7)-MeG was also associated with a decreased 1-min Apgar score (beta = -0.25, p = 0.042). Mutual adjustment for iAs and N(7)-MeG showed an independent and significant prediction for a decreased 1-min Apgar score of iAs (beta = -0.28, p = 0.036). Maternal iAs exposure was associated with both maternal DNA damage and adverse newborn health. Maternal N(7)-MeG levels might be a novel biomarker for monitoring fetal health related to iAs.

The association between total urinary arsenic concentration and renal dysfunction in a community-based population from central Taiwan.

Arsenic (As) is an important environmental toxicant that can cause cancer and cardiovascular disease, but the relationship between As exposure and renal dysfunction is not clear. The aim of this study is to examine the association between As exposure and renal dysfunction in a community-based population in central Taiwan. One thousand and forty-three subjects were recruited between 2002 and 2005. The risk for type 2 diabetes was increased by 2-fold (p<0.05) in subjects with total urinary As (U-As)>75 µg g(-1) creatinine as compared with subjects whose U-As was ≤ 35 µg g(-1) creatinine after the adjustment for potential confounders. The adjusted odds ratio for an abnormal ß2 microglobulin (B2MG>0.154 mg L(-1)) was significantly higher in subjects with U-As>35 µg g(-1) creatinine as compared with the reference group adjusted for age, sex, living area, cigarette smoking, diabetes, and hypertension. The risk for abnormal B2MG and estimated glomerular filtration rate (eGFR<90 mL min(-1)(1.73 m(2))(-1)) was both increased around 2-fold (p<0.05) in subjects with U-As>75 µg g(-1) creatinine as compared with those with U-As ≤ 35 µg g(-1) creatinine adjusted for all the risk factors plus lead (Pb), cadmium and nickel. The prevalence of abnormal B2MG was 4.82 times higher in subjects with both over the median levels of U-As (85.1 µg L(-1)) and urinary Pb (18.9 µg L(-1)) as compared to both lower than the median (p<0.001). These results indicate that U-As might relate to renal dysfunction even other important risk factors were taken into account. Follow-up studies for causal inference are warranted.

Alkylphenols in human milk and their relations to dietary habits in central Taiwan.

The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure.

Relationship between insulin sensitivity and exposure to dioxins and polychlorinated biphenyls in pregnant women.

The aim of this study was to examine the relationship between insulin sensitivity and polychlorinated biphenyls (PCBs) exposure in non-diabetic pregnant women. Forty gravidas, 21-39 years of age and residing within the study area, were recruited. Seventeen 2,3,7,8-substituted dichloro-p-dioxin, dibenzofurans and 12 PCBs were measured using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Serum insulin and glucose were also measured. Insulin sensitivity and the quantitative insulin sensitivity check index (QUICKI) were calculated based on fasting glucose and insulin levels. Three specific congeners of PCBs (123, 126, and 169) were significantly associated with insulin activity (r=-0.34 approximately -0.36, p<0.05). Statistical analyses revealed that insulin sensitivity was significantly associated with age- and pre-pregnancy body mass indices (BMI)-adjusted for decreasing toxic equivalents (TEQ) of PCBs (p=0.02 for age- and BMI-adjusted). We also performed an insulin correlation for total TEQ and the TEQ of PCBs, and determined that insulin sensitivity was predicted by the TEQ of PCBs by a regression coefficient of -0.189 after adjustment for age and pre-pregnancy BMI. These findings suggest that PCBs may be associated with decreasing insulin sensitivity in non-diabetic pregnant women; however, the mechanism remains to be ascertained.

Inhibition of bovine herpesvirus-4 replication in endothelial cells by arsenite.

The effect of arsenite pretreatment on bovine herpesvirus-4 (BHV-4) replication in bovine arterial endothelial (BAE) cells was studied. BHV-4 infectivity, including IE-2 expression, DNA replication and viral yield, were significantly reduced at nontoxic concentrations of arsenite in which cellular DNA synthesis or cell viability of BAE cells were not affected under resting and confluent conditions. This effect was accompanied by the induction of heat shock protein 70 (HSP70) and an interrupted cell cycle (causing cell cultures to accumulate at the S and G2/M phases). Actinomycin D inhibited the induction of HSP70 and reduced arsenite antiviral activity. In conclusion, cellular stress response induced by arsenite in BAE cells inhibited replication of BHV-4, and probably resulted from the induction of HSP70 and interference of cell cycle progression.

Inhibition of bovine herpesvirus-4 replication by arsenite through downregulation of the extracellular signal-regulated kinase signaling pathway.

Infection of bovine arterial endothelial (BAE) cells with bovine herpesvirus-4 (BHV-4) induced biphasic activation of one of the cellular mitogen-activated protein kinase (MAPK) downstream targets, extracellular signal-regulated kinase (ERK). ERK activity reached a maximum within 0.5 h postinfection (h.p.i.), and had declined and returned to basal levels by 2 h.p.i. However, at 18- 24 h.p.i., a second phase of increased ERK activation occurred. Treatment of BHV-4-infected BAE cells with either U0126, a potent inhibitor of MAPK/ERK kinase, or arsenite dose-dependently blocked ERK activation and inhibited viral DNA synthesis and viral replication in the culture. Further detailed investigations revealed that transcription of viral immediate-early gene 2 (IE-2), which is required for viral DNA replication, was significantly suppressed by both U0126 and arsenite. These results imply that ERK activation may play a pivotal role in herpesvirus replication, and that inhibition of ERK activation can effectively inhibit viral IE protein synthesis and viral replication.

4G/5G promoter polymorphism of plasminogen activator inhibitor-1, lipid profiles, and ischemic stroke.

The 4G allele of common 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with increased PAI-1 transcription and has been proposed as a candidate genetic risk factor for thrombotic diseases. We investigated the relationship between this polymorphism and lipid profiles and stroke risk. One hundred patients with ischemic stroke and 150 age- and sex-matched control subjects were enrolled. PAI-1 genotype was determined with the use of polymerase chain reaction and restriction-length analysis. Genotype distribution in the stroke group was 40% 4G/4G, 46% 4G/5G, and 14% 5G/5G; in the control group it was 38.7% 4G/4G, 45.3% 4G/5G, and 16% 5G/5G. The allele and genotype frequencies of 4G/5G polymorphism were not different between the stroke and control groups. Control subjects who were homozygous for the 4G allele had significantly lower high-density lipoprotein (HDL) cholesterol levels than did those carrying the 5G allele (51.2 +/- 11.8 vs 58.4 +/- 15.8 mg/dL; P =.002). In the control group, regression analysis revealed a significant contribution of 4G/4G genotype to increased triglyceride (P =.042) and to decreased HDL cholesterol (P <.001) levels. Our findings suggest that PAI-1 4G/5G promoter polymorphism alone is not associated with ischemic stroke. However, this polymorphism influences lipid levels, and the underlying mechanism must be determined.