Effects of ambient air pollution on pulmonary function among schoolchildren

Literature has shown adverse effects of ambient air pollution exposure on various asthma related outcomes in childhood. However, the associated evidence on pulmonary function effects is still inconsistent.We conducted a population-based study comprised of seventh-grade children in 14 Taiwanese communities. Pulmonary function tests and questionnaires were completed on 3957 subjects. We evaluated the effects of ambient air pollution exposures based on the data collected in 2005–2007 by existing air monitoring stations. Multiple linear mixed effect models were fitted to estimate the relationship between community pollutant levels and pulmonary function indices. After adjustment for individual-level confounders, pulmonary function differed only slightly between communities with different levels of air pollution. We found greater effects of ambient air pollutants on pulmonary function for boys than for girls. Among boys, traffic-related pollutants CO, NOx, NO₂, and NO were generally associated with chronic adverse effects on FVC and FEV₁, and subchronic adverse effects mainly on maximal mid-expiratory flow (MMEF) and peak expiratory flow rate. Among girls, only NOx and NO₂ showed subchronic adverse effects on MMEF. Although effect estimates of SO₂, PM₁₀, and PM_2.5 were generally negative for boys, none achieved statistical significance.Our data suggests that ambient traffic-related pollution had chronic adverse effects on pulmonary function in schoolchildren, especially for boys.     

Noise, air pollutants and traffic: continuous measurement and correlation at a high-traffic location in New York City

Background

Epidemiological studies have linked both noise and air pollution to common adverse health outcomes such as increased blood pressure and myocardial infarction. In urban settings, noise and air pollution share important sources, notably traffic, and several recent studies have shown spatial correlations between noise and air pollution. The temporal association between these exposures, however, has yet to be thoroughly investigated despite the importance of time series studies in air pollution epidemiology and the potential that correlations between these exposures could at least partly confound statistical associations identified in these studies.Methods: An aethelometer, for continuous elemental carbon measurement, was co-located with a continuous noise monitor near a major urban highway in New York City for six days in August 2009. Hourly elemental carbon measurements and hourly data on overall noise levels and low, medium and high frequency noise levels were collected. Hourly average concentrations of fine particles and nitrogen oxides, wind speed and direction and car, truck and bus traffic were obtained from nearby regulatory monitors. Overall temporal patterns, as well as day–night and weekday–weekend patterns, were characterized and compared for all variables.

Results

Noise levels were correlated with car, truck, and bus traffic and with air pollutants. We observed strong day–night and weekday–weekend variation in noise and air pollutants and correlations between pollutants varied by noise frequency. Medium and high frequency noise were generally more strongly correlated with traffic and traffic-related pollutants than low frequency noise and the correlation with medium and high frequency noise was generally stronger at night. Correlations with nighttime high frequency noise were particularly high for car traffic (Spearman rho=0.84), nitric oxide (0.73) and nitrogen dioxide (0.83). Wind speed and direction mediated relationships between pollutants and noise.

Conclusions

Noise levels are temporally correlated with traffic and combustion pollutants and correlations are modified by the time of day, noise frequency and wind. Our results underscore the potential importance of assessing temporal variation in co-exposures to noise and air pollution in studies of the health effects of these urban pollutants.     

Particulate air pollution, oxidative stress genes, and heart rate variability in an elderly cohort

BACKGROUND AND OBJECTIVES: We have previously shown that reduced defenses against oxidative stress due to glutathione S-transferase M1 (GSTM1) deletion modify the effects of PM(2.5) (fine-particulate air pollution of < 2.5 microm in aerodynamic diameter) on heart rate variability (HRV) in a cross-sectional analysis of the Normative Aging Study, an elderly cohort. We have extended this to include a longitudinal analysis with more subjects and examination of the GT short tandem repeat polymorphism in the heme oxygenase-1 (HMOX-1) promoter. METHODS: HRV measurements were taken on 539 subjects. Linear mixed effects models were fit for the logarithm of HRV metrics-including standard deviation of normal-to-normal intervals (SDNN), high frequency (HF), and low frequency (LF)-and PM(2.5) concentrations in the 48 hr preceding HRV measurement, controlling for confounders and a random subject effect. RESULTS: PM(2.5) was significantly associated with SDNN (p = 0.04) and HF (p = 0.03) in all subjects. There was no association in subjects with GSTM1, whereas there was a significant association with SDNN, HF, and LF in subjects with the deletion. Similarly, there was no association with any HRV measure in subjects with the short repeat variant of HMOX-1, and significant associations in subjects with any long repeat. We found a significant three-way interaction of PM(2.5) with GSTM1 and HMOX-1 determining SDNN (p = 0.008), HF (p = 0.01) and LF (p = 0.04). In subjects with the GSTM1 deletion and the HMOX-1 long repeat, SDNN decreased by 13% [95% confidence interval (CI), -21% to -4%], HF decreased by 28% (95% CI, -43% to -9%), and LF decreased by 20% (95% CI, -35% to -3%) per 10 microg/m(3) increase in PM. CONCLUSIONS: Oxidative stress is an important pathway for the autonomic effects of particles.     

Maternal smoking during pregnancy, polymorphic CYP1A1 and GSTM1, and lung-function measures in urban family children

Purpose

Understanding the interplay between genes and in-utero tobacco exposure in affecting child lung development is of great significance. In this study, we tested the hypothesis that tobacco-related lung-function reduction in children differs by maternal polymorphic genes Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase Mu 1 (GSTM1).

Materials and methods

Data were collected among 370 children (6–10 years old, 81.6% African-Americans) and their biological mothers visiting a large children’s hospital. Study hypotheses were tested using multiple regression method.

Results

Among the study sample, 143 mothers smoked throughout pregnancy and 72 smoked on a daily basis. Spirometric measures (mean±SD) included were: forced vital capacity (FVC)=1635±431 mL, forced expiratory volume in the first 1 s (FEV₁)=1440 ±360 mL, percent FEV₁/FVC ratio=89±12, and forced expiratory flow between the 25% and 75% of FVC (FEF_25–75)=1745±603 mL. In addition to a tobacco effect on FVC (−131 mL, 95% CI: −245, −17) and FEV₁/FVC ratio (42, 95% CI: 1, 83), regression analysis controlling for covariates indicated that for the subsample of children whose mothers were CYP1A1?2A homozygous, maternal daily smoking was associated with −734 mL (95% CI: −1206, −262) reductions in FEV₁ and −825 mL (95% CI: −909, −795) reductions in FVC; reduced smoking was still associated with −590 mL (95% CI: −629, −551) reductions in FVC. For children of mothers with GSTM1 deletion, persistent daily smoking was associated with −176 mL (95% CI: −305, −47) reductions in FVC.

Discussion and conclusions

Maternal smoking during pregnancy was significantly associated with lung-function reduction in children, particularly for those whose mothers possessed the polymorphic CYP1A1*2A and GSTM1 deletion.     

The influence of location, source, and emission type in estimates of the human health benefits of reducing a ton of air pollution

The benefit per ton ($/ton) of reducing PM_2.5 varies by the location of the emission reduction, the type of source emitting the precursor, and the specific precursor controlled. This paper examines how each of these factors influences the magnitude of the $/ton estimate. We employ a reduced-form air quality model to predict changes in ambient PM_2.5 resulting from an array of emission control scenarios affecting 12 different combinations of sources emitting carbonaceous particles, NO _x , SO _x , NH₃, and volatile organic compounds. We perform this modeling for each of nine urban areas and one nationwide area. Upon modeling the air quality change, we then divide the total monetized health benefits by the PM_2.5 precursor emission reductions to generate $/ton metrics. The resulting $/ton estimates exhibit the greatest variability across certain precursors and sources such as area source SO _x , point source SO _x , and mobile source NH₃. Certain $/ton estimates, including mobile source NO _x , exhibit significant variability across urban areas. Reductions in carbonaceous particles generate the largest $/ton across all locations.     

Respiratory Health Effects of Airborne Particulate Matter: The Role of Particle Size, Composition, and Oxidative Potential-The RAPTES Project

Background: Specific characteristics of particulate matter (PM) responsible for associations with respiratory health observed in epidemiological studies are not well established. High correlations among, and differential measurement errors of, individual components contribute to this uncertainty.Objectives: We investigated which characteristics of PM have the most consistent associations with acute changes in respiratory function in healthy volunteers.Methods: We used a semiexperimental design to accurately assess exposure. We increased exposure contrast and reduced correlations among PM characteristics by exposing volunteers at five different locations: an underground train station, two traffic sites, a farm, and an urban background site. Each of the 31 participants was exposed for 5 hr while exercising intermittently, three to seven times at different locations during March-October 2009. We measured PM10, PM2.5, particle number concentrations (PNC), absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and PM oxidative potential. Lung function [FEV1 (forced expiratory volume in 1 sec), FVC (forced vital capacity), FEF25-75 (forced expiratory flow at 25-75% of vital capacity), and PEF (peak expiratory flow)] and fractional exhaled nitric oxide (FENO) were measured before and at three time points after exposure. Data were analyzed with mixed linear regression.Results: An interquartile increase in PNC (33,000 particles/cm3) was associated with an 11% [95% confidence interval (CI): 5, 17%] and 12% (95% CI: 6, 17%) FENO increase over baseline immediately and at 2 hr postexposure, respectively. A 7% (95% CI: 0.5, 14%) increase persisted until the following morning. These associations were robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between FVC and FEV1 with PNC, NO2 (nitrogen dioxide), and NOx (nitrogen oxides).Conclusions: Changes in PNC, NO2, and NOx were associated with evidence of acute airway inflammation (i.e., FENO) and impaired lung function. PM mass concentration and PM10 oxidative potential were not predictive of the observed acute responses.     

Health impact assessment of increasing public transport and cycling use in Barcelona: A morbidity and burden of disease approach

Objective

Quantify the health impacts on morbidity of reduced car trips and increased public transport and cycling trips.

Methods

A health impact assessment study of morbidity outcomes related to replacing car trips in Barcelona metropolitan (3,231,458 inhabitants). Through 8 different transport scenarios, the number of cases of disease or injuries related to physical activity, particulate matter air pollution < 2.5 μm (PM_2.5) and traffic incidents in travelers was estimated. We also estimate PM_2.5 exposure and cases of disease in the general population.

Results

A 40% reduction in long-duration car trips substituted by public transport and cycling trips resulted in annual reductions of 127 cases of diabetes, 44 of cardiovascular diseases, 30 of dementia, 16 minor injuries, 0.14 major injuries, 11 of breast cancer and 3 of colon-cancer, amounting to a total reduction of 302 Disability Adjusted Life Years per year in travelers. The reduction in PM_2.5 exposure in the general population resulted in annual reductions of 7 cases of low birth weight, 6 of preterm birth, 1 of cardiovascular disease and 1 of lower respiratory tract infection.

Conclusions

Transport policies to reduce car trips could produce important health benefits in terms of reduced morbidity, particularly for those who take up active transportation.     

Indoor environmental quality in school buildings,and the health and wellbeing of students

Poor indoor environmental quality (IEQ) in classrooms may be a risk for health symptoms and cause absence from school. We conducted a comprehensive study in order to assess the connection between IEQ in Finnish elementary school buildings and the health and academic performance of sixth grade students. The specific aim of the present paper was to study the school- or grade-level prevalence of symptoms in relation to IEQ. The school- or grade-level (i.e. group level) prevalence of self-reported symptoms and perceived IEQ was studied using data collected by a health questionnaire comprising 37 questions. The health questionnaire was sent to all 6th grade students in a stratified random sample of 355 elementary schools in Finland. Indoor environmental conditions were assessed with measurements of ventilation rate and thermal conditions of classrooms in a subsample of 56 schools. Altogether 297 elementary schools participated in the health questionnaire study and a total of 4248 questionnaires were returned (estimated response rate 62.6%). The most common weekly symptoms in the spring semester were fatigue (7.7%), stuffy nose (7.3%), and headache (5.5%). However, both mean prevalence values for different symptoms among all 6th grade students and group-level prevalence values for specific symptoms varied considerably. On the group level, the prevalence values most frequently found above 95% CI (calculated for N = 15) were wheezing, cough with wheezing, and fever over 37 °C. The most frequently reported IEQ factors causing daily inconvenience in classrooms were noise (11.0%) and stuffy air/poor indoor air quality (IAQ) (7.0%), which were also found most frequently above 95% CI on the group level (calculated for N = 15), together with self-reported high indoor temperature and dust or dirtiness. Self-reported daily stuffiness/poor IAQ was significantly correlated with measured mean temperatures and ventilation rates in classrooms. High prevalence of students’ self-reported stuffiness/poor IAQ may indicate high indoor temperature or low ventilation rate in classrooms. Also high group level prevalence of other IEQ factors and certain symptoms may be indicative of IEQ problems that should be further studied. The results of this study can be used as a reference for assessing the questionnaire-based prevalence of self-reported symptoms among 6th graders, and their association with IEQ in classrooms. For such assessment, the number of students responding to the questionnaire must be carefully considered, also bearing in mind that prevalence values are symptom specific.     

Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections

Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with Streptococcus pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-γ which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete.     

Assessment of HPV 16 and HPV 18 antibody responses by pseudovirus neutralization,Merck cLIA and Merck total IgG LIA immunoassays in a reduced dosage quadrivalent HPV vaccine trial

We assessed HPV 16 and 18 antibody responses of female subjects enrolled in a 2- vs. 3-dose quadrivalent HPV (Q-HPV) vaccine trial (ClinicalTrials.gov NCT00501137) using the Merck competitive Luminex (cLIA) and total IgG Luminex (TIgG) immunoassays, and a pseudovirus neutralizing antibody (PsV NAb) assay. Subjects were enrolled in one of three groups: (1) 9–13 yr, 2 doses of Q-HPV at 0, 6 months (n = 259); (2) 9–13 yr, 3 doses at 0, 2, 6 months (n = 260); and (3) 16–26 yr, 3 doses at 0, 2, 6 months (n = 305). Sera were collected from all subjects at baseline, months 7 and 24, and from half the subjects at months 18 and 36. High correlation was observed between all three assays. At month 36, HPV 16 antibodies remained detectable in all subjects by all assays, whereas 86.4%, 99.6% and 100% of subjects respectively were HPV 18 cLIA, TIgG and PsV NAb (partial neutralization endpoint) seropositive. The proportion seropositive for HPV 18 by cLIA at 36 months was not significantly different for 2-dose girls vs. 3-dose adults (85.9% vs. 79.4%; p = 0.51), whereas the proportion for 3-dose girls was significantly higher than for 3-dose adults (95.3% vs. 79.4%; p < 0.01). The HPV 18 seropositive proportions by the TIgG and PsV NAb (partial neutralization endpoint) assays were the same for all subjects. High baseline HPV 16 and HPV 18 seropositivity was observed for the TIgG assay and it is unclear if all the detected TIgG antibodies are type-specific and/or neutralizing. For the PsV NAb assay, 90% and partial neutralization geometric mean titres were consistently 2–8-fold higher than for 100% neutralization, which enabled detection of HPV 18 NAb in subjects who lost detectable cLIA antibodies over time. We conclude that the PsV NAb assay is more sensitive than the cLIA, and likely more specific than the TIgG assay.     

Association of Serum Pyridoxal-5′-Phosphate,Pyridoxal, and PAr with Colorectal Cancer Risk: A Large-Scale Case-Control Study

Previous epidemiological studies have focused on the association of dietary vitamin B₆ or circulating pyridoxal-5′-phosphate (PLP) with colorectal cancer risk. This study aimed to investigate the vitamin B₆ in relation to colorectal cancer risk combining the biomarkers of PLP, pyridoxal (PL) plus PLP, and PAr (the ratio of 4-pyridoxic acid over the sum of PLP and PL). A large-scale hospital-based case-control study was conducted in Guangdong Province, China, which included 1233 colorectal cancer cases and 1245 sex and age frequency-matched controls. Serum PLP, PL, and 4-pyridoxic acid (PA) were detected with ultra-high-performance liquid chromatography–tandem mass spectrometry. Unconditional logistic regression models were used to assess the odds ratios (ORs) and 95% confidence intervals (95% CIs). Serum PLP and the sum of PLP and PL were inversely associated with colorectal cancer risk, while PAr was positively associated with colorectal cancer risk. Comparing the highest with the lowest quartile, the adjusted OR (95% CI) was 0.26 (0.20–0.33, P_trend < 0.001) for serum PLP, 0.51 (0.40–0.66, P_trend < 0.001) for serum PLP plus PL, and 2.90 (2.25–3.75, P_trend < 0.001) for PAr. Serum PLP and PAr had significantly stronger associations with colorectal cancer risk in the male group and smoking group. Our results supported the protective role of vitamin B₆ in colorectal cancer risk among Chinese people. The positive association of PAr with colorectal cancer risk suggested the potential role of inflammation and oxidative stress in colorectal carcinogenesis.     

Interlaboratory Evaluation of in Vitro Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: The NIEHS Nano GO Consortium

Background: Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity.Objectives: Grantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability.Methods: Consortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO₂), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different species (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1β (IL-1β) release] using only THP-1 cells.Results: The overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 μg/mL, but did not induce IL-1β. TiO₂ was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1β production in THP-1 cells, with the original MWCNT producing the most IL-1β.Conclusions: The results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity.     

Determinants of arsenic metabolism: blood arsenic metabolites, plasma folate, cobalamin, and homocysteine concentrations in maternal-newborn pairs

BACKGROUND: In Bangladesh, tens of millions of people have been consuming waterborne arsenic for decades. The extent to which As is transported to the fetus during pregnancy has not been well characterized. OBJECTIVES: We therefore conducted a study of 101 pregnant women who gave birth in Matlab, Bangladesh. METHODS: Maternal and cord blood pairs were collected and concentrations of total As were analyzed for 101 pairs, and As metabolites for 30 pairs. Maternal urinary As metabolites and plasma folate, cobalamin, and homocysteine levels in maternal cord pairs were also measured. Household tube well-water As concentrations exceeded the World Health Organization guideline of 10 microg/L in 38% of the cases. RESULTS: We observed strong associations between maternal and cord blood concentrations of total As (r = 0.93, p < 0.0001). Maternal and cord blood arsenic metabolites (n = 30) were also strongly correlated: in dimethylarsinate (DMA) (r = 0.94, p < 0.0001), monomethylarsonate (r = 0.80, p < 0.0001), arsenite (As(+3)) (r = 0.80, p < 0.0001), and arsenate (As(+5)) (r = 0.89, p < 0.0001). Maternal homocysteine was a strong predictor of %DMA in maternal urine, maternal blood, and cord blood (beta = -6.2, p < 0.02; beta = -10.9, p < 0.04; and beta = -13.7, p < 0.04, respectively). Maternal folate was inversely associated with maternal blood As(5+) (beta = 0.56, p < 0.05), and maternal cobalamin was inversely associated with cord blood As(5+) (beta = -1.2, p < 0.01). CONCLUSIONS: We conclude that exposure to all metabolites of inorganic As occurs in the prenatal period.     

Atmospheric mercury in Changbai Mountain area, northeastern China II. The distribution of reactive gaseous mercury and particulate mercury and mercury deposition fluxes

Reactive gaseous mercury (RGM) and particulate mercury (Hgp) concentrations in ambient air from a remote site at Changbai Mountain area in northeastern China were intermittently monitored from August 2005 to July 2006 totaling 93 days representing fall, winter-spring and summer season, respectively. Rainwater and snow samples were collected during a whole year, and total mercury (THg) in rain samples were used to calculate wet depositional flux. A throughfall method and a model method were used to estimate dry depositional flux. Results showed mean concentrations of RGM and Hgp are 65 and 77 pg m⁻³. Compared to background concentrations of atmospheric mercury species in Northern Hemisphere, RGM and Hgp are significantly elevated in Changbai area. Large values for standard deviation indicated fast reactivity and a low residence time for these mercury species. Seasonal variability is also important, with lower mercury levels in summer compared to other seasons, which is attributed to scavenging by rainfall and low local mercury emissions in summer. THg concentrations ranged from 11.5 to 15.9 ng L⁻¹ in rainwater samples and 14.9-18.6 ng L⁻¹ in throughfall samples. Wet depositional flux in Changbai area is calculated to be 8.4 μg m⁻² a⁻¹, and dry deposition flux is estimated to be 16.5 μg m⁻² a⁻¹ according to a throughfall method and 20.2 μg m⁻² a⁻¹ using a model method.     

Nutritional supplement attenuates selected oxidative stress markers in pediatric patients with cystic fibrosis

Our aim was to test the hypothesis that nutritional supplement (AquADEKs; Axcan Scandipharm Inc., Birmingham, Ala, USA) with various pharmaceutical forms of such as chewable tablets, capsules, and liquid administered daily for 12 weeks would reduce oxidative stress and enhance antioxidant status in pediatric patients with cystic fibrosis (CF). A total of 50 patients with CF and 21 healthy children were included in the study. Patients were divided into 4 groups: group A received supplementation with vitamins A (3 mg daily), E (200 mg daily), and D₃ (20 μg daily); group B was supplemented with AquADEKs chewable tablets; group C received the recommended amount of AquADEKs capsules; and group D was supplemented with AquADEKs liquid. The level of oxidative stress was determined by the analysis of activities of enzymes neutralizing reactive oxygen species and by the estimated markers of intensity of free radical processes. There was no difference in the activity of erythrocyte catalase, hydroperoxides level, and sulfhydryl group content in blood plasma between patients with CF and healthy children. The plasma total antioxidant status was decreased in all CF groups compared with the control. The supplementation with either AquADEKs chewable tablets or capsules normalized the malondialdehyde level in plasma. AquADEKs in various pharmaceutical forms normalized the sulfhydryl group content of erythrocytes. The superoxide dismutase activity was increased to near control level in the patients supplemented with either AquADEKs chewable tablets or liquid as compared with the group supplemented with vitamins or with AquADEKs capsules. In conclusion, AquADEKs attenuates selected oxidative stress markers in pediatric patients with CF.     

Immunogenicity and safety of Fluzone intradermal and high-dose influenza vaccines in older adults ≥65 years of age: A randomized,controlled, phase II trial

We conducted a randomized, controlled, multicenter, phase II study to evaluate the immunogenicity and safety of an investigational intradermal (ID) trivalent influenza vaccine (TIV) and a high-dose (HD) intramuscular (IM) TIV in older adults (≥65 years of age). Older adult subjects were immunized with ID vaccine containing either 15 μg hemagglutinin (HA)/strain (n = 636) or 21 μg HA/strain (n = 634), with HD IM vaccine containing 60 μg HA/strain (n = 320), or with standard-dose (SD) IM vaccine (Fluzone^®; 15 μg HA/strain; n = 319). For comparison, younger adults (18–49 years of age) were immunized with SD IM vaccine. In older adults, post-vaccination geometric mean titers induced by the ID vaccines were superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains and non-inferior for the B strain. Seroconversion rates induced by the ID vaccines were superior to those induced by the SD IM vaccine in older adults for the A/H1N1 and B strains and non-inferior for the A/H3N2 strain. Results did not differ significantly for the two ID vaccine dosages. Post-vaccination geometric mean titers, seroconversion rates, and most seroprotection rates were significantly higher in HD vaccine recipients than in older adult recipients of the SD IM or ID vaccines and, for most measures, were comparable to those of younger adult SD IM vaccine recipients. Injection-site reactions, but not systemic reactions or unsolicited adverse events, were more common with the ID vaccines than with the IM vaccines. No treatment-related serious adverse events were reported. This study demonstrated that: (1) the ID and HD vaccines were well-tolerated and more immunogenic than the SD IM vaccine in older adults; (2) the HD vaccine was more immunogenic than the ID vaccines in older adults; and (3) the HD vaccine in older adults and the SD IM vaccine in younger adults elicited comparable antibody responses (ClinicalTrials.gov identifier no.: NCT00551031).     

Study of selenium intake and disposition in various matrices based on mathematical algorithms derived from pooled biomonitoring data

Biomonitoring is increasingly used to assess exposure to selenium (Se) in the population. However, there is little harmonization among protocols used in the different studies (varying biological matrices, differences in expression of results (concentrations versus amounts, units)). This makes inter-comparison of biomonitoring results across studies difficult. From a public health risk perspective, it also becomes challenging to estimate baseline levels in biological matrices for populations exposed by various sources. The aim of this study was thus to perform a systematic analysis of the relationship between Se intakes and biological concentrations based on published data. Inclusion and exclusion criteria were used and led to select 75 published biomonitoring data in humans from an extended review of Se biomonitoring studies. This represents 8 628 individuals who provided biological samples aiming at documenting Se exposure and/or Se concentrations in two or more biological matrices. Mathematical algorithms that relate Se intakes to biological concentrations and establish matrix-to-matrix associations were derived from these pooled biomonitoring data. Logarithmic regressions showed good correlations between Se intakes and whole blood concentrations (R² = 0.884), plasma concentrations (R² = 0.863) and urinary excretion rates (R² = 0.958). Blood and plasma concentrations were also strongly related (R² = 0.874), as were whole blood concentrations and urinary excretion rates (R² = 0.953). The interpretation of the log-regression coefficients allowed illustrating Se physiology. Se concentrations in plasma tend to plateau when daily intake exceed 150 μg/d, whereas Se in urine increases rapidly above this threshold. The application of the algorithms to other independent data sets in order to reconstruct past Se intakes confirmed that interpretation of results on the basis of Se in integuments may be misleading if external contamination is not avoided. This approach based on pooled data covered a wide range of exposure and the large number of data integrated increased the level of confidence of results.     

Aqueous extract of tamarind seeds selectively increases glucose transporter-2, glucose transporter-4, and islets' intracellular calcium levels and stimulates β-cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes mellitus

Tamarindus indica Linn. has been in use for a long time in Asian food and traditional medicine for different diseases including diabetes and obesity. However, the molecular mechanisms of these effects have not been fully understood. In view of the multidimensional activity of tamarind seeds due to their having high levels of polyphenols and flavonoids, we hypothesized that the insulin mimetic effect of aqueous tamarind seed extract (TSE) might increase glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family and sterol regulatory element-binding proteins (SREBP) 1c messenger RNA (mRNA) in the liver. Daily oral administration of TSE to streptozotocin (STZ)–induced (90 mg/kg intraperitoneally) type 2 diabetic male Wistar rats at different doses (120 and 240 mg/kg body weight) for 4 weeks showed positive correlation with intracellular calcium and insulin release in isolated islets of Langerhans. Tamarind seed extract supplementation significantly improved the GLUT-2 protein and SREBP-1c mRNA expression in the liver and GLUT-4 protein and mRNA expression in the skeletal muscles of diabetic rats. The elevated levels of serum nitric oxide (NO), glycosylated hemoglobin level (hemoglobin _A1c) and tumor necrosis factor α (TNF-α) decreased after TSE administration. Immunohistochemical findings revealed that TSE abrogated STZ-induced apoptosis and increased β-cell neogenesis, indicating its effect on islets and β-cell mass. In conclusion, it was found that the antidiabetic effect of TSE on STZ-induced diabetes resulted from complex mechanisms of β-cell neogenesis, calcium handling, GLUT-2, GLUT-4, and SREBP-1c. These findings show the scope for formulating a new herbal drug for diabetes therapy.     

Production of catalytically inactive BoNT/A1 holoprotein and comparison with BoNT/A1 subunit vaccines against toxin subtypes A1, A2, and A3

A recombinant, catalytically inactive Clostridium botulinum neurotoxin A1 holoprotein (ciBoNT/A1 HP) was constructed by introducing amino acid substitutions H223A, E224A, and H227A in the active site to ablate proteolytic activity. ciBoNT/A1 HP was produced in the yeast Pichia pastoris and the purified product was evaluated as a vaccine candidate by comparison against recombinant BoNT/A1 LC, LC-belt, LC-H_n, and H_c antigens and a LC-H_n + H_c combination in mouse potency and efficacy bioassays when challenged with BoNT/A subtypes /A1, /A2, and /A3. A single dose of ciBoNT/A1 HP provided equivalent or greater protective immunity, not only against the homologous toxin, but also against two distinct toxin subtypes with significant amino acid divergence. Only the LC-H_n + H_c combination provided comparable protection against /A1; however, it was less effective against subtypes /A2 and /A3. Differences in protective immunity diminished after multiple vaccinations with either ciBoNT/A1 HP or BoNT/A1 H_c, and the survival rates were more comparable at the toxin levels used to challenge.