Is combined peritoneal dialysis and hemodialysis redundant? A nationwide study from Taiwan.

BACKGROUND: Combined peritoneal dialysis (PD) and hemodialysis (HD) therapy (combined therapy) has numerous clinical benefits and should be emphasized for PD patients encountering technique failure. METHODS: This 12-year nationwide retrospective study was conducted to compare long-term outcomes (including admission and mortality risks) between combined therapy patients (combined group) and patients directly transferred from PD to HD (transfer group). RESULTS: All 12,407 incidental PD patients from 2000 to 2010 were enrolled and followed up until the end of 2011. A total of 688 patients in the combined group and 688 patients in the transfer group were selected after 1:1 frequency matching based on age, sex, and PD duration. The overall admission and mortality risks of the two groups were comparable in a Cox proportional hazards model (adjusted hazard ratio [HR] = 1.06 [95% confidence interval (CI) = 0.95-1.19] and 1.02 [95% CI = 0.80-1.30]), respectively). Compared with the transfer group, combined group patients with recent peritonitis or frequent hemodialysis (four HD sessions per month) had significantly higher risk of admission while combined group patients without peritonitis had significantly lower risk. The number of incidents in the combined group increased over time. On average, patients stayed on combined therapy for 2 years. CONCLUSIONS: Combined therapy (two HD sessions per month) is not redundant but a rational and cost-effective treatment, particularly for patients without recent peritonitis. Dialysis staff should be familiar with the advantages and disadvantages of combined therapy and consider it an essential part of integrated dialysis care.

Probabilistic risk and benefit assessment of nitrates and nitrites by integrating total diet study-based exogenous dietary exposure with endogenous nitrite formation using toxicokinetic modeling.

The impacts of dietary nitrates and nitrites on human health have been a controversial topic for many years. However, the risk and benefit assessment of nitrates and nitrites is complicated by the large variation in nitrate and nitrite intake among people and the endogenous nitrite formation in the body. This study conducted a probabilistic risk-benefit assessment of dietary nitrates and nitrites based on internal dose by integrating exogenous and endogenous exposures with human trial data on cardiovascular benefits. A total diet study was carried out to quantify the age-specific dietary intakes of nitrates and nitrites. A previously well-validated human toxicokinetic model was used to predict internal doses for different age groups. In addition, the integrated approach was applied to different populations from different countries/regions based on reported exposure estimates to conduct a comprehensive risk-benefit assessment of dietary nitrates and nitrites. The results demonstrated that vegetable consumption was the main contributor to the internal nitrate and nitrite levels in all age groups. Exposure to nitrates and nitrites exceeding acceptable daily intakes in a variety of foods showed cardiovascular benefits. The probabilistic risk assessment showed that the exposure to nitrates and nitrites did not pose an appreciable health and safety risk. Therefore, the present results suggest that dietary nitrates and nitrites have clear cardiovascular benefits that may outweigh potential risks. Our analysis contributes significantly to addressing the controversy regarding risks and benefits from dietary nitrates and nitrites, and our approach could be applied to other dietary constituents with the potential for both risks and benefits.

Exposure to Ambient NO2 Increases the Risk of Dry Eye Syndrome in Females: An 11-Year Population-Based Study.

Previous studies have indicated that women suffer from dry eye syndrome (DES) more significantly than men. Therefore, we specifically explore the associations between air pollutant levels and the risks of DES for women. The study obtained 27,605 participants from the 29 recruitment centers of the Taiwan Biobank, which was established in October 2012. A large scale cross-sectional study involving DES sufferers and age- and education-matched control groups without DES was designed. Based on the municipality of residence, the predicted concentration levels of various air pollutants, including PM2.5, sulfur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2) were estimated by using hybrid kriging/LUR model. Multiple logistic regressions were applied to estimate the prevalence ratios (PR) of DES and 95% confidence interval. Hormone supplementations, DBP, allergies, and arthritis were considered as important comorbidities for increased PR risk of DES. In addition, with each standard deviation (SD) increment of PM2.5 and temperature, women had significant increases in PRs of DES of 1.09- and 1.07-fold, respectively; conversely, each SD increment of relative humidity (RH) had a protective effect against the risk of DES. After considering hormone supplementation, arthritis, and allergy, the SD increment of NO2 and temperature were associated with the PRs of DES. In conclusion, significant associations of ambient NO2 concentration, RH and temperature with DES indicated the importance of increased environmental protection in the female population. Female exposure to high levels of NO2 when receiving hormone supplementation, or suffering with allergies or arthritis, had significantly increased risk of DES.

Growth and thyroid function in children with in utero exposure to dioxin: a 5-year follow-up study.

Because placental polychlorinated dibenzo-p-dioxins,dibenzofurans (PCDD/Fs) levels are associated with decreased free thyroxine (FT(4)) and thyroid stimulating hormone (TSH) in neonates, we assessed development by gender and maternal PCDD/Fs exposure at years 2 and 5 in 92 mother and newborn pairs. RIA quantified thyroid, sex, and growth hormones. Of 200 subjects followed up from November 2000, 136 and 149 were observed at year 2 and year 5,respectively. PCDD/Fs exposure levels were low (n = 35) or high (n = 35) in 70 subjects at year 2, low (n = 21) or high (n = 20) in 41 at year 5. Height, weight, BMI, and head circumference were significantly higher in males, chest girth significantly higher in females at year 2. Significantly, more girls had higher bone age (BA) and chronological age (CA) at both times. Height, weight, FT(4) x TSH, and transthyretin(TTR) at year 2; and height, triiodothyronine, and IGF-1 at year 5 differed significantly by PCDD/Fs level. In females, height, weight, CA,BA, and thyroid hormones differed significantly at year 2. In males, FT(4) x TSH at year 2 and IGF-1 at year 5 were significantly higher in the high PCDD/Fs group. In utero exposure to PCDD/Fs differentially affects growth and hormone levels in male and female preschool children.

Incorporating Exogenous and Endogenous Exposures into Dietary Risk Assessment of Nitrates and Nitrites in Vegetables: A Probabilistic Integrated Toxicokinetic Modeling Approach.

This study aimed to estimate the dietary risk of nitrates and nitrites in vegetables based on internal dose in a probabilistic manner by integrating exogenous exposure based on measured concentrations in vegetables with endogenous exposure using a toxicokinetic (TK) model. We optimized and validated a previous TK model and incorporated Monte Carlo simulations to account for variability across different age populations for predicting internal dose. High levels of nitrates were detected in leafy vegetables (from 545 ± 274 to 1641 ± 873 mg/kg). Nitrite contents of vegetables were generally low (from 1.26 ± 1.40 to 8.20 ± 14.1 mg/kg). The dietary risk was found to be different based on internal versus external dose, suggesting that it is critical to include endogenous nitrite formation into risk assessment. Nitrate and nitrite exposure from vegetables is unlikely to result in appreciable risks for most populations but may be a potential risk for preschoolers.

Ecosystem metabolism regulates seasonal bioaccumulation of metals in atyid shrimp (Neocaridina denticulata) in a tropical brackish wetland.

Natural dissolved organic matter (DOM) forms the base of aquatic food webs and is a key environmental factor that affects the bioavailability of metals for aquatic organisms. Aquatic communities are naturally exposed simultaneously to environments containing a mixture of metals and varying DOM levels and compositions. However, the exact effect of DOM on metal bioaccumulation is difficult to predict due to temporal and spatial variations in sources, production, and consumption of DOM, and to interactions between DOM and metals. Ecosystem metabolism describes the process of organic carbon production and consumption and, therefore, the trophic status of ecosystems. However, whether and how ecosystem metabolism determines the seasonality of metal bioaccumulation remains unclear. The present study used in-situ water quality sondes and discrete field samplings to establish the relationship between the seasonality of ecosystem metabolism; related environmental and limnological regulators; the metal speciation and concentration in bulk water and sediments; and their metal bioaccumulation. The target population consisted of atyid shrimp (Neocaridina denticulata) in a brackish constructed wetland in tropical Taiwan was sampled between August 2014 and November 2015. Metal bioaccumulation displayed distinct seasonal patterns that peaked in summer (Cu, Cd, Cr, Zn, Mn, and Se) or winter (Pb and Ni). The in situ production (gross primary production) and heterotrophic consumption (ecosystem respiration) of organic matter significantly decreased with increasing waterborne DOM levels in this heterotrophic wetland. Both dissolved free metals bioavailable for respiratory surfaces (As, Zn, Cu, and Cr) and insoluble metals available for dietary intake (Mn and Ni) decreased with increasing DOM, as well as with decreasing gross primary production and ecosystem respiration. Seasonal variations of metal bioaccumulation also paralleled the transition in wetland trophic status, which reflected the effect of potential qualitative changes in the wetland DOM pool. Bioaccumulation of most metals displayed strong correlations with gross primary production, ecosystem respiration, and wetland trophic status. Our findings demonstrated that ecosystem metabolism can play a key mediating role in the seasonality of metal bioaccumulation in atyid shrimp, as it links the variation and interaction between DOM level/source, the speciation/bioavailability, and the uptake efficiency for metals by aquatic organisms. This study contributes to the temporal-specific risk assessment of aquatic metal exposure in regional environmental settings. It also reveals ecosystem-specific spectra in the context of changes in climate and environment.

Population physiologically based pharmacokinetic modeling for the human lactational transfer of PCB-153 with consideration of worldwide human biomonitoring results.

BACKGROUND: One of the most serious human health concerns related to environmental contamination with polychlorinated biphenyls (PCBs) is the presence of these chemicals in breast milk. OBJECTIVES: We developed a physiologically based pharmacokinetic model of PCB-153 in women, and predict its transfer via lactation to infants. The model is the first human, population-scale lactational model for PCB-153. Data in the literature provided estimates for model development and for performance assessment. METHODS: We used physiologic parameters from a cohort in Taiwan and reference values given in the literature to estimate partition coefficients based on chemical structure and the lipid content in various body tissues. Using exposure data from Japan, we predicted acquired body burden of PCB-153 at an average childbearing age of 25 years and compared predictions to measurements from studies in multiple countries. We attempted one example of reverse dosimetry modeling using our PBPK model for possible exposure scenarios in Canadian Inuits, the population with the highest breast milk PCB-153 level in the world. RESULTS: Forward-model predictions agree well with human biomonitoring measurements, as represented by summary statistics and uncertainty estimates. CONCLUSION: The model successfully describes the range of possible PCB-153 dispositions in maternal milk, suggesting a promising option for back-estimating doses for various populations.

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.

Body burden of dioxins and dioxin-like polychlorinated biphenyls in pregnant women residing in a contaminated area.

A large pentachlorophenol (PCP)-manufacturing plant located in southwestern Taiwan operated between 1965 and 1982. The present study was conducted to ascertain whether an increased body burden of dioxins existed in pregnant women living in an area of Tainan city contaminated by chemicals from this plant. Twenty-eight pregnant subjects, 21-39 years of age and residing in the study area between March and December of 2004 with a mean dwelling time of 6.07+/-6.11 years, were recruited. Concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (PCBs) in serum of recruited residents were determined. Pregnant women residing in the study area >3 years had significantly higher PCDD (7.48 versus 5.13 pg-toxic equivalents [TEQ]/g-lipid) and dioxin-like PCB (6.70 versus 3.74 pg-TEQ/g-lipid) values as compared to those residing < or = 3 years. Furthermore, dioxin concentrations increased with increasing dwelling time. Statistical analyses performed according to demographic characteristics and socioeconomic and dietary habits revealed that total TEQ values were significantly associated with fish consumption and smoking status. Dioxin congeners with greater degrees of chlorine substitution (e.g., HpCDD/F and OCDD/F) partitioned to greater degrees in the subjects of this study as compared to subjects in the general Taiwanese population. The findings of this study strongly implicate the activity of the PCP manufacturing plant in the observed increase in dioxin body burden. Investigation of the health consequences of this increased body burden is recommended.

Contribution of inorganic arsenic sources to population exposure risk on a regional scale.

Chronic exposure to inorganic arsenic (iAs) in the human population is associated with various internal cancers and other adverse outcomes. The purpose of this study was to estimate a population-scale exposure risk attributable to iAs consumptions by linking a stochastic physiological-based pharmacokinetic (PBPK) model and biomonitoring data of iAs in urine. The urinary As concentrations were obtained from a total of 1,043 subjects living in an industrial area of Taiwan. The results showed that the study subjects had an iAs exposure risk of 27 % (the daily iAs intake for 27 % study subjects exceeded the WHO-recommended value, 2.1 µg iAs day(-1) kg(-1) body weight). Moreover, drinking water and cooked rice contributed to the iAs exposure risk by 10 and 41 %, respectively. The predicted risks in the current study were 4.82, 27.21, 34.69, and 64.17 %, respectively, among the mid-range of Mexico, Taiwan (this study), Korea, and Bangladesh reported in the literature. In conclusion, we developed a population-scale-based risk model that covered the broad range of iAS exposure by integrating stochastic PBPK modeling and reverse dosimetry to generate probabilistic distribution of As intake corresponding to urinary As measured from the cohort study. The model can also be updated as new urinary As information becomes available.

Linking biokinetics and consumer-resource dynamics of zinc accumulation in pond abalone Haliotis diversicolor supertexta.

A dynamic model that links biokinetics and consumer-resource dynamics for describing zinc (Zn) accumulation in abalone Haliotis diversicolor supertexta has been developed and then applied to Zn data from real abalone farms. The biokinetic parameters used in this study, uptake and depuration rate constants of abalone and their food source, red alga Gracilaria tenuistipitata var. liui, were obtained from a laboratory 14-d exposure experiment. We carried out a sensitivity analysis of the model by using the fractional factorial design technique, taking into account the influence of consumer-resource-related parameters such as growth and death rates and biomass and biokinetic parameters characterized by bioconcentration factor. Results indicate that the response time of biomagnification dynamics of Zn accumulation in abalone was influenced mainly by the growth rate of algae and biomass and the death rate of abalone and by interactions algae biomass and abalone death rate and abalone and algae biomass. New algae production results in substantially higher values of biomagnification factor. The linked model was then applied to field observations from a real-life situation of variable Zn concentrations occurring in abalone farms. Simulation results show that the predicted values are within a factor of 2 of the measured values (% errors range from 5.3 +/- 4% to 44.1+/- 8%). Both model analysis and model application to the abalone farms suggest that the linking influences between biokinetics and consumer-resource dynamics support Zn accumulation in H. diversicolor supertexta and in G. tenuistipitata var. liui as functions of Zn concentration in water and abundance of food occurring in abalone farms.

Compartmental human respiratory tract modeling of airborne dust exposure from feeding in swine buildings.

A simple size-dependent compartmental model was developed to describe airborne dust exposure dynamics for the human respiratory tract (HRT) in mechanically ventilated swine buildings. Transport mechanisms of airborne dust for HRT include respiration, gravitational settling, turbulent diffusive deposition, inertial impaction, interception deposition loss, and dust clearance. The dominant deposition mechanism in the lung regions was found to be the inertial impaction rate, in which the order of magnitude ranged from 10(-3) to 10(-1) sec(-1). Results demonstrate that the extrathoracic region has a higher airborne dust mass lung/indoor ratios (0.71-0.87) than do the bronchial regions (0.41-0.74), the bronchiolar region (0.12-0.61), and the alveolar-interstitial region (0.01-0.49). The predictions from the HRT model agreed favorably with the experimental deposition profiles in the nasal passage, pharynx, bronchial, bronchiolar, and alveolar-interstitial regions, whereas the rms errors of the total deposition fraction between predicted values and ICRP66 and Non-ICRP66 were 0.15 and 0.07, respectively. Simulation results show that breathing via the nose has both a higher deposition fraction and a higher exposure dose in the size ranges 0.01-10 microm than does breathing orally.

Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions.

In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 µg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 µg m(-3)) and Western (21.47 ± 11.44 µg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 µg m(-3)), followed by Western (0.86 ± 1.43 µg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 µg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6).

Arsenic methylation, GSTO1 polymorphisms, and metabolic syndrome in an arseniasis endemic area of southwestern Taiwan.

Previous studies have shown that hair arsenic (As) levels are associated with an increased prevalence of metabolic syndrome (MetS), which is a strong predictor for type 2 diabetes. The objective of this study was to evaluate whether urinary arsenic methylation is related to MetS in an arseniasis endemic area of southwestern Taiwan, taking genetic factors into account. Subjects were from a community-based cohort recruited in 1990 from three villages in Putai Township. In 2002-2003, we successfully followed 247 subjects and measured their urinary arsenic species including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the coding region polymorphisms of three genes known to involve in arsenic methylation. Results showed that subjects of MetS had a history of consuming well water of higher arsenic concentration as compared to those without MetS. We also found a significant association between urinary arsenic species and risk for MetS, where the odds ratio of MetS was increased with decreasing proportion of MMA and low rate of primary methylation (defined as MMA/inorganic As). The increased risk associated with low primary methylation rate was further modified by the GSTO1 A140D polymorphism, with the D allele carriers showing a slightly higher risk for MetS. Our results suggest that a low MMA% is associated with increased risk for MetS among As-exposed subjects and the genetic polymorphism of GSTO1, an enzyme responsible for the reduction of pentavalent arsenic species, may also play a modest modification role.

Phthalate exposure in pregnant women and their children in central Taiwan.

Phthalate exposure was found to be associated with endocrine disruption, respiratory effects, reproductive and developmental toxicity. The intensive use of plastics may be increasing the exposure to phthalates in Taiwanese population, particularly for young children. We studied phthalate metabolites in pregnant women and their newborns in a prospective cohort from a medical center in Central Taiwan. One hundred maternal urine samples and 30 paired cord blood and milk samples were randomly selected from all of participants (430 pregnant women). Eleven phthalate metabolites (MEHP, 5OH-MEHP, 2cx-MEHP, 5cx-MEPP, 5oxo-MEHP, MiBP, MnBP, MBzP, OH-MiNP, oxo-MiNP, and cx-MiNP) representing the exposure to five commonly used phthalates (DEHP, di-isobutyl phthalate (DiBP), DnBP, BBP, DiNP) were measured in urine of pregnant women, cord serum and breast milk after delivery, and in urine of their children. Exposure was estimated with excretion factors and correlation among metabolites of the same parent compound. Thirty and 59 urinary samples from 2 and 5 years-old children were randomly selected from 185 children successfully followed. Total urinary phthalate metabolite concentration (geometric mean, µg L⁻¹) was found to be higher in 2-years-olds (398.6) and 5-years-olds (333.7) than pregnant women (205.2). Metabolites in urine are mainly from DEHP. The proportion of DiNP metabolites was higher in children urine (4.39 and 8.31%, ages 2 and 5) than in adults (0.83%) (p<0.01). Compared to urinary levels, phthalate metabolite levels are low in cord blood (37.45) and milk (14.90). DEHP metabolite levels in women's urine and their corresponding cord blood are significantly correlated. Compared to other populations in the world, DEHP derived metabolites in maternal urine were higher, while phthalate metabolite levels in milk and cord blood were similar. The level of phthalate metabolites in milk and cord blood were comparable to those found in other populations. Further studies of health effects related to DEHP and DiNP exposure are necessary for the children.

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.

Hypertension incidence after tap-water implementation: a 13-year follow-up study in the arseniasis-endemic area of southwestern Taiwan.

Hypertension is the leading cause of cardiovascular disease worldwide. Long-term arsenic exposure has been linked to increased risk for hypertension; however, little is known whether a previous exposure has lingering effects on hypertension after the exposure being reduced significantly for decades. The study cohort was established in 1990 in an arseniasis-endemic area of 3 villages - Homei, Fuhsin, and Hsinming in Putai Township located on the southwestern coast of Taiwan, where residents were exposed to artesian well water (median level=700 to 930 µg/L) until early 1970s. The original cohort consisted of 490 non-hypertensive residents over 30-yrs-old and 352 of them were successfully followed up in 2002/03. Arsenic concentrations in the artesian well water consumed by residents during 1960s were used to indicate the previous exposure while urinary arsenic species measured in 2002/3 was used to represent current exposure. Hypertension incidences were 27.4, 65.6, and 69.1, per 1000 person-years for men aged 35-49, 50-64, and 65-74 years, respectively being higher than the corresponding rates of 25.1, 46.1, and 57.2 in a community-based longitudinal study. Cancer was the major cause of the total deaths (17/30=57%). Diastolic blood pressure was shown to increase with an increased cumulative arsenic ingestion from drinking water (ß=0.27, p<0.001). The incidence was increased by 2.43-fold in subjects of As(V)≥2.67 µg/g creatinine as compared to those of As(V)<1.20 µg/g creatinine (the third vs. first tertile; p=0.047) after adjustment for conventional risk factors. This study suggests that three decades after cessation of drinking artesian well water, residents of the endemic area are still at increased risk for developing hypertension, particularly those who excrete high amounts of As(V).

Computational and ultrastructural toxicology of a nanoparticle, Quantum Dot 705, in mice.

We conducted pharmacokinetic and toxicology studies on Quantum Dot 705 (QD705) in male ICR mice for up to 6 months after a single intravenous dose. Time-course sacrifices were carried out at 1, 4, and 24 h; 3, 7, 14, and 28 days; and 6 months on groups of six mice per time point. Mass balance studies were also carried out at 24 h, 28 days, and 6 months. Using inductively coupled plasma mass spectrometry, various tissues, urine, and feces were analyzed for cadmium (Cd111), which is a major (46%) component of QD705. On the basis of these experimental studies, a physiologically based pharmacokinetic computer simulation model was developed with excellent predictive capability for the time-dependent kinetic and distributional changes of QD705 in tissues. QD705 persisted and accumulated in the spleen, liver, and kidneys for at least 28 days with little or no disposition but was gradually and partially eliminated by 6 months. Although histological alterations of the spleen, liver, and kidney by light microscopy are unremarkable, investigation using electron microscopy on numerous renal samples revealed definitive mitochondrial alterations in renal tubular epithelial cells at 28 days and 6 months postdosing. Health implications and potential beneficial applications of QD705 are suggested.

Glutathione regulation of redox-sensitive signals in tumor necrosis factor-alpha-induced vascular endothelial dysfunction.

We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-alpha)-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-alpha induces various biological effects on vascular cells, TNF-alpha dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-alpha concentrations, we adopted the lower TNF-alpha (0.2 ng/ml) to rule out the possible involvement of other TNF-alpha-induced biological effects. Inhibition of glutathione synthesis by l-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-alpha-induced adhesion molecule expression and monocyte-endothelial monolayer binding. BSO attenuated the TNF-alpha-induced nuclear factor-kappaB (NF-kappaB) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-alpha. Inhibition of ERK, JNK, or NF-kappaB attenuates TNF-alpha-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-alpha induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-kappaB in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-alpha. Although AP-1 activation by the lower TNF-alpha was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-alpha-induced adhesion molecule expression.

Microbial degradation of livestock-generated ammonia using biofilters at typical ambient temperatures.

The purpose of this research was to neutralize livestock-generated ammonia by using biofilters packed with inexpensive inorganic and organic packing material combined with multicultural microbial load at typical ambient temperatures. Peat and inorganic supporting materials were used as biofiltration matrix packed in a perfusion column through which gas was transfused. Results show the ammonia removal significantly fell in between 99 and 100% when ammonia concentration of 200 ppmv was used at different gas flow rates ranged from 0.030 to 0.060 m3 h(-1) at a fluctuating room temperature of 27.5 +/- 4.5 C (Mean +/- SD). Under these conditions, the emission concentration of ammonia that is liberated after biofiltration is less than 1 ppmv (0.707 mg m(-3)) over the period of our study, suggesting the usage of low-cost biofiltration systems for long-term function is effective at wider ranges of temperature fluctuations. The maximum (100%) ammonia removal efficiency was obtained in this biofilter was having an elimination capacity of 2.217 g m(-3) h(-1). This biofilter had high nitrification efficiencies and hence controlled ammonia levels with the reduced backpressure. The response of this biofilter to shut down and start up operation showed that the biofilm has a superior stability.