Estimation of Short-Term Effects of Air Pollution on Stroke Hospital Admissions in Wuhan,China

Background and Objective

High concentrations of air pollutants have been linked to increased incidence of stroke in North America and Europe but not yet assessed in mainland China. The aim of this study is to evaluate the association between stroke hospitalization and short-term elevation of air pollutants in Wuhan, China.

Methods

Daily mean NO₂, SO₂ and PM₁₀ levels, temperature and humidity were obtained from 2006 through 2008. Data on stroke hospitalizations (ICD 10: I60–I69) at four hospitals in Wuhan were obtained for the same period. A time-stratified case-crossover design was performed by season (April-September and October-March) to assess effects of pollutants on stroke hospital admissions.

Results

Pollution levels were higher in October-March with averages of 136.1 µg/m³ for PM₁₀, 63.6 µg/m³ for NO₂ and 71.0 µg/m³ for SO₂ than in April-September when averages were 102.0 µg/m³, 41.7 µg/m³ and 41.7 µg/m³, respectively (p<.001). During the cold season, every 10 µg/m³ increase in NO₂ was associated with a 2.9% (95%C.I. 1.2%–4.6%) increase in stroke admissions on the same day. Every 10 ug/m³ increase in PM₁₀ daily concentration was significantly associated with an approximate 1% (95% C.I. 0.1%–1.4%) increase in stroke hospitalization. A two-pollutant model indicated that NO₂ was associated with stroke admissions when controlling for PM₁₀. During the warm season, no significant associations were noted for any of the pollutants.

Conclusions

Exposure to NO₂ is significantly associated with stroke hospitalizations during the cold season in Wuhan, China when pollution levels are 50% greater than in the warm season. Larger and multi-center studies in Chinese cities are warranted to validate our findings.     

Intracellular Conversion of Environmental Nitrate and Nitrite to Nitric Oxide with Resulting Developmental Toxicity to the Crustacean Daphnia magna

Background

Nitrate and nitrite (jointly referred to herein as NO_x) are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NO_x undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes.

Methodology/Principal Findings

These experiments were performed with insect cells (Drosophila S2) and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO₃ ⁻) and nitrite (NO₂ ⁻) to nitric oxide using amperometric real-time nitric oxide detection. Both NO₃ ⁻ and NO₂ ⁻ were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO₂ ⁻ to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control) and to concentrations of NO₃ ⁻ and NO₂ ⁻. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers.

Conclusions/Significance

Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide.     

Non-invasive measurements of exhaled NO and CO associated with methacholine responses in mice

Background

Nitric oxide (NO) and carbon monoxide (CO) in exhaled breath are considered obtainable biomarkers of physiologic mechanisms. Therefore, obtaining their measures simply, non-invasively, and repeatedly, is of interest, and was the purpose of the current study.

Methods

Expired NO (E_NO) and CO (E_CO) were measured non-invasively using a gas micro-analyzer on several strains of mice (C57Bl6, IL-10^-/-, A/J, MKK3^-/-, JNK1^-/-, NOS-2^-/- and NOS-3^-/-) with and without allergic airway inflammation (AI) induced by ovalbumin systemic sensitization and aerosol challenge, compared using independent-sample t-tests between groups, and repeated measures analysis of variance (ANOVA) within groups over time of inflammation induction. E_NO and E_CO were also measured in C57Bl6 and IL-10-/- mice, ages 8–58 weeks old, the relationship of which was determined by regression analysis. S-methionyl-L-thiocitrulline (SMTC), and tin protoporphyrin (SnPP) were used to inhibit neuronal/constitutive NOS-1 and heme-oxygenase, respectively, and alter NO and CO production, respectively, as assessed by paired t-tests. Methacholine-associated airway responses (AR) were measured by the enhanced pause method, with comparisons by repeated measures ANOVA and post-hoc testing.

Results

E_NO was significantly elevated in naïve IL-10^-/- (9–14 ppb) and NOS-2^-/- (16 ppb) mice as compared to others (average: 5–8 ppb), whereas E_CO was significantly higher in naïve A/J, NOS-3^-/- (3–4 ppm), and MKK3^-/- (4–5 ppm) mice, as compared to others (average: 2.5 ppm). As compared to C57Bl6 mice, AR of IL-10^-/-, JNK1^-/-, NOS-2^-/-, and NOS-3^-/- mice were decreased, whereas they were greater for A/J and MKK3^-/- mice. SMTC significantly decreased E_NO by ~30%, but did not change AR in NOS-2^-/- mice. SnPP reduced E_CO in C57Bl6 and IL-10^-/- mice, and increased AR in NOS-2^-/- mice. E_NO decreased as a function of age in IL-10^-/- mice, remaining unchanged in C57Bl6 mice.

Conclusion

These results are consistent with the ideas that: 1) E_NO is associated with mouse strain and knockout differences in NO production and AR, 2) alterations of E_NO and E_CO can be measured non-invasively with induction of allergic AI or inhibition of key gas-producing enzymes, and 3) alterations in AR may be dependent on the relative balance of NO and CO in the airway.     

Bronchial responsiveness is related to increased exhaled NO (FE(NO)) in non-smokers and decreased FE(NO) in smokers

Rationale

Both atopy and smoking are known to be associated with increased bronchial responsiveness. Fraction of nitric oxide (NO) in the exhaled air (FE_NO), a marker of airways inflammation, is decreased by smoking and increased by atopy. NO has also a physiological bronchodilating and bronchoprotective role.

Objectives

To investigate how the relation between FE_NO and bronchial responsiveness is modulated by atopy and smoking habits.

Methods

Exhaled NO measurements and methacholine challenge were performed in 468 subjects from the random sample of three European Community Respiratory Health Survey II centers: Turin (Italy), Gothenburg and Uppsala (both Sweden). Atopy status was defined by using specific IgE measurements while smoking status was questionnaire-assessed.

Main Results

Increased bronchial responsiveness was associated with increased FE_NO levels in non-smokers (p = 0.02) and decreased FE_NO levels in current smokers (p = 0.03). The negative association between bronchial responsiveness and FE_NO was seen only in the group smoking less <10 cigarettes/day (p = 0.008). Increased bronchial responsiveness was associated with increased FE_NO in atopic subjects (p = 0.04) while no significant association was found in non-atopic participants. The reported interaction between FE_NO and smoking and atopy, respectively were maintained after adjusting for possible confounders (p-values<0.05).

Conclusions

The present study highlights the interactions of the relationship between FE_NO and bronchial responsiveness with smoking and atopy, suggesting different mechanisms behind atopy- and smoking-related increases of bronchial responsiveness.     

Interaction between Advanced Glycation End Products Formation and Vascular Responses in Femoral and Coronary Arteries from Exercised Diabetic Rats

Background

The majority of studies have investigated the effect of exercise training (TR) on vascular responses in diabetic animals (DB), but none evaluated nitric oxide (NO) and advanced glycation end products (AGEs) formation associated with oxidant and antioxidant activities in femoral and coronary arteries from trained diabetic rats. Our hypothesis was that 8-week TR would alter AGEs levels in type 1 diabetic rats ameliorating vascular responsiveness.

Methodology/Principal Findings

Male Wistar rats were divided into control sedentary (C/SD), sedentary diabetic (SD/DB), and trained diabetic (TR/DB). DB was induced by streptozotocin (i.p.: 60 mg/kg). TR was performed for 60 min per day, 5 days/week, during 8 weeks. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (PHE) and tromboxane analog (U46619) were obtained. The protein expressions of eNOS, receptor for AGEs (RAGE), Cu/Zn-SOD and Mn-SOD were analyzed. Tissues NO production and reactive oxygen species (ROS) generation were evaluated. Plasma nitrate/nitrite (NO_x ⁻), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and N^ε-(carboxymethyl) lysine (CML, AGE biomarker). A rightward shift in the concentration-response curves to ACh was observed in femoral and coronary arteries from SD/DB that was accompanied by an increase in TBARS and CML levels. Decreased in the eNOS expression, tissues NO production and NO_x ⁻ levels were associated with increased ROS generation. A positive interaction between the beneficial effect of TR on the relaxing responses to ACh and the reduction in TBARS and CML levels were observed without changing in antioxidant activities. The eNOS protein expression, tissues NO production and ROS generation were fully re-established in TR/DB, but plasma NO_x ⁻ levels were partially restored.

Conclusion

Shear stress induced by TR fully restores the eNOS/NO pathway in both preparations from non-treated diabetic rats, however, a massive production of AGEs still affecting relaxing responses possibly involving other endothelium-dependent vasodilator agents, mainly in coronary artery.     

Auxin distribution is differentially affected by nitrate in roots of two rice cultivars differing in responsiveness to nitrogen

Background and Aims

Although ammonium (NH₄⁺) is the preferred form of nitrogen over nitrate (NO₃⁻) for rice (Oryza sativa), lateral root (LR) growth in roots is enhanced by partial NO₃⁻ nutrition (PNN). The roles of auxin distribution and polar transport in LR formation in response to localized NO₃⁻ availability are not known.

Methods

Time-course studies in a split-root experimental system were used to investigate LR development patterns, auxin distribution, polar auxin transport and expression of auxin transporter genes in LR zones in response to localized PNN in ‘Nanguang’ and ‘Elio’ rice cultivars, which show high and low responsiveness to NO₃⁻, respectively. Patterns of auxin distribution and the effects of polar auxin transport inhibitors were also examined in DR5::GUS transgenic plants.

Key Results

Initiation of LRs was enhanced by PNN after 7 d cultivation in ‘Nanguang’ but not in ‘Elio’. Auxin concentration in the roots of ‘Nanguang’ increased by approx. 24 % after 5 d cultivation with PNN compared with NH₄⁺ as the sole nitrogen source, but no difference was observed in ‘Elio’. More auxin flux into the LR zone in ‘Nanguang’ roots was observed in response to NO₃⁻ compared with NH₄⁺ treatment. A greater number of auxin influx and efflux transporter genes showed increased expression in the LR zone in response to PNN in ‘Nanguang’ than in ‘Elio’.

Conclusions

The results indicate that higher NO₃⁻ responsiveness is associated with greater auxin accumulation in the LR zone and is strongly related to a higher rate of LR initiation in the cultivar ‘Nanguang’.     

Comparison between NO(x) Evolution Mechanisms of Wild-Type and nr(1) Mutant Soybean Leaves

The nr₁ soybean (Glycine max [L.] Merr.) mutant does not contain the two constitutive nitrate reductases, one of which is responsible for enzymic conversion of nitrite to NO_x (NO + NO₂). It was tested for possible nonenzymic NO_x formation and evolution because of known chemical reactions between NO₂⁻ and plant metabolites and the instability of nitrous acid. It did not evolve NO_x during the in vivo NR assay, but intact leaves did evolve small amounts of NO_x under dark, anaerobic conditions. Experiments were conducted to compare NO₃⁻ reduction, NO₂⁻ accumulation, and the NO_x evolution processes of the wild type (cv Williams) and the nr₁ mutant. In vivo NR assays showed that wild-type leaves had three times more NO₃⁻ reducing capacity than the nr₁ mutant. NO_x evolution from intact, anerobic nr₁ leaves was approximately 10 to 20% that from wild-type leaves. Nitrite content of the nr₁ mutant leaves was usually higher than wild type due to low NO_x evolution. Lag times and threshold NO₂⁻ concentrations for NO_x evolution were similar for the two genotypes. While only 1 to 2% of NO_x from wild type is NO₂, the nr₁ mutant evolved 15 to 30% NO₂. The kinetic patterns of NO_x evolution with time weré completely different for the mutant and wild type. Comparisons of light and heat treatments also gave very different results. It is generally accepted that the NO_x evolution by wild type is primarily an enzymic conversion of NO₂⁻ to NO. However, this report concludes that NO_x evolution by the nr₁ mutant was due to nonenzymic, chemical reactions between plant metabolites and accumulated NO₂⁻ and/or decomposition of nitrous acid. Nonenzymic NO_x evolution probably also occurs in wild type to a degree but could be easily masked by high rates of the enzymic process.     

Association between Traffic-Related Air Pollution,Subclinical Inflammation and Impaired Glucose Metabolism: Results from the SALIA Study

Background

Environmental and lifestyle factors regulate the expression and release of immune mediators. It has been hypothesised that ambient air pollution may be such an external factor and that the association between air pollution and impaired glucose metabolism may be attributable to inflammatory processes. Therefore, we assessed the associations between air pollution, circulating immune mediators and impaired glucose metabolism.

Methods

We analysed concentrations of 14 pro- and anti-inflammatory immune mediators as well as fasting glucose and insulin levels in plasma of 363 women from the Study on the influence of Air pollution on Lung function, Inflammation and Aging (SALIA, Germany). Exposure data for a group of pollutants such as nitrogen oxides (NO₂, NO_x) and different fractions of particulate matter were available for the participants'' residences. We calculated the association between the pollutants and impaired glucose metabolism by multiple regression models.

Results

The study participants had a mean age of 74.1 (SD 2.6) years and 48% showed impaired glucose metabolism based on impaired fasting glucose or previously diagnosed type 2 diabetes. Only long-term exposure NO₂ and NO_x concentrations showed positive associations (NO₂: OR 1.465, 95% CI 1.049-2.046, NO_x: OR 1.409, 95% CI 1.010-1.967) per increased interquartile range of NO₂ (14.65 µg/m³) or NO_x (43.16 µg/m³), respectively, but statistical significance was lost after correction for multiple comparisons. Additional adjustment for circulating immune mediators or the use of anti-inflammatory medication had hardly any impact on the observed ORs.

Conclusions

Our results suggest that exposure to nitrogen oxides may contribute to impaired glucose metabolism, but the associations did not reach statistical significance so that further studies with larger sample sizes are required to substantiate our findings. Our data do not preclude a role of inflammatory mechanisms in adipose or other tissues which may not be reflected by immune mediators in plasma.     

Evaluation of the Shape Symmetry of Bilateral Normal Corneas in a Chinese Population

Purpose

To investigate the bilateral symmetry of the global corneal topography in normal corneas with a wide range of curvature, astigmatism and thickness values

Design

Cross-Sectional Study

Methods

Topography images were recorded for the anterior and posterior surfaces of 342 participants using a Pentacam. Elevation data were fitted to a general quadratic model that considered both translational and rotational displacements. Comparisons between fellow corneas of estimates of corneal shape parameters (elevation, radius in two main directions, R_x and R_y, and corresponding shape factors, Q_x and Q_y) and corneal position parameters (translational displacements: x₀, y₀ and z₀, and rotational displacements: α, β and γ) were statistically analyzed.

Results

The general quadratic model provided average RMS of fit errors with the topography data of 1.7±0.6 µm and 5.7±1.3 µm in anterior and posterior corneal surfaces. The comparisons showed highly significant bilateral correlations with the differences between fellow corneas in R_x, R_y, Q_x and Q_y of anterior and posterior surfaces remaining insignificantly different from zero. Bilateral differences in elevation measurements at randomly-selected points in both corneal central and peripheral areas indicated strong mirror symmetry between fellow corneas. The mean geometric center (x₀, y₀, z₀) of both right and left corneas was located on the temporal side and inferior-temporal side of the apex in anterior and posterior topography map, respectively. Rotational displacement angle α along X axis had similar distributions in bilateral corneas, while rotation angle β along Y axis showed both eyes tilting towards the nasal side. Further, rotation angle γ along Z axis, which is related to corneal astigmatism, showed clear mirror symmetry.

Conclusions

Analysis of corneal topography demonstrated strong and statistically-significant mirror symmetry between bilateral corneas. This characteristic could help in detection of pathological abnormalities, disease diagnosis, measurement validation and surgery planning.     

The Single-Breath Diffusing Capacity of CO and NO in Healthy Children of European Descent

Rationale

The diffusing capacity (D_L) of the lung can be divided into two components: the diffusing capacity of the alveolar membrane (Dm) and the pulmonary capillary volume (Vc). D_L is traditionally measured using a single-breath method, involving inhalation of carbon monoxide, and a breath hold of 8–10 seconds (D_L,CO). This method does not easily allow calculation of Dm and Vc. An alternative single-breath method (D_L,CO,NO), involving simultaneous inhalation of carbon monoxide and nitric oxide, and traditionally a shorter breath hold, allows calculation of Dm and Vc and the D_L,NO/D_L,CO ratio in a single respiratory maneuver. The clinical utility of Dm, Vc, and D_L,NO/D_L,CO in the pediatric age range is currently unknown but also restricted by lack of reference values.

Objectives

The aim of this study was to establish reference ranges for the outcomes of D_L,CO,NO with a 5 second breath hold, including the calculated outcomes Dm, Vc, and the D_L,NO/D_L,CO ratio, as well as to establish reference values for the outcomes of the traditional D_L,CO method, with a 10 second breath hold in children.

Methods

D_L,CO,NO and D_L,CO were measured in healthy children, of European descent, aged 5–17 years using a Jaeger Masterscreen PFT. The data were analyzed using the Generalized Additive Models for Location Scale and Shape (GAMLSS) statistical method.

Measurements and Main Results

A total of 326 children were eligible for diffusing capacity measurements, resulting in 312 measurements of D_L,CO,NO and 297 of D_L,CO, respectively. Reference equations were established for the outcomes of D_L,CO,NO and D_L,CO, including the calculated values: Vc, Dm, and the D_L,NO/D_L,CO ratio.

Conclusion

These reference values are based on the largest sample of children to date and may provide a basis for future studies of their clinical utility in differentiating between alterations in the pulmonary circulation and changes in the alveolar membrane in pediatric patients.     

Vascular Relaxation Induced by C-Type Natriuretic Peptide Involves the Ca2+/NO-Synthase/NO Pathway

Aims

C-type natriuretic peptide (CNP) and nitric oxide (NO) are endothelium-derived factors that play important roles in the regulation of vascular tone and arterial blood pressure. We hypothesized that NO produced by the endothelial NO-synthase (NOS-3) contributes to the relaxation induced by CNP in isolated rat aorta via activation of endothelial NPR-C receptor. Therefore, the aim of this study was to investigate the putative contribution of NO through NPR-C activation in the CNP induced relaxation in isolated conductance artery.

Main Methods

Concentration-effect curves for CNP were constructed in aortic rings isolated from rats. Confocal microscopy was used to analyze the cytosolic calcium mobilization induced by CNP. The phosphorylation of the residue Ser¹¹⁷⁷ of NOS was analyzed by Western blot and the expression and localization of NPR-C receptors was analyzed by immunohistochemistry.

Key Findings

CNP was less potent in inducing relaxation in denuded endothelium aortic rings than in intact ones. L-NAME attenuated the potency of CNP and similar results were obtained in the presence of hydroxocobalamin, an intracellular NO⁰ scavenger. CNP did not change the phosphorylation of Ser¹¹⁷⁷, the activation site of NOS-3, when compared with control. The addition of CNP produced an increase in [Ca²⁺]_c in endothelial cells and a decrease in [Ca²⁺]_c in vascular smooth muscle cells. The NPR-C-receptors are expressed in endothelial and adventitial rat aortas.

Significance

These results suggest that CNP-induced relaxation in intact aorta isolated from rats involves NO production due to [Ca²⁺]_c increase in endothelial cells possibly through NPR-C activation expressed in these cells. The present study provides a breakthrough in the understanding of the close relationship between the vascular actions of nitric oxide and CNP.     

Clinical patterns in asthma based on proximal and distal airway nitric oxide categories

Background

The exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J''aw_NO (nl/s), maximum airway flux] and distal contributions [CA_NO (ppb), distal airway/alveolar NO concentration]. We hypothesized that J''aw_NO and CA_NO are selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features.

Methods

In 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J''aw_NO and CA_NO.

Results

J''aw_NO was not correlated with CA_NO, and thus asthmatic subjects were grouped into four eNO categories based on upper limit thresholds of non-asthmatics for J''aw_NO (≥ 1.5 nl/s) and CA_NO (≥ 2.3 ppb): Type I (normal J''aw_NO and CA_NO), Type II (elevated J''aw_NO and normal CA_NO), Type III (elevated J''aw_NO and CA_NO) and Type IV (normal J''aw_NO and elevated CA_NO). The rate of inhaled corticosteroid use (lowest in Type III) and atopy (highest in Type II) varied significantly amongst the categories influencing J''aw_NO, but was not related to CA_NO, asthma control or morbidity. All categories demonstrated normal to near-normal baseline spirometry; however, only eNO categories with increased CA_NO (III and IV) had significantly worse asthma control and morbidity when compared to categories I and II.

Conclusions

J''aw_NO and CA_NO reveal inflammatory categories in children with asthma that have distinct clinical features including sensitivity to inhaled corticosteroids and atopy. Only categories with increase CA_NO were related to poor asthma control and morbidity independent of baseline spirometry, bronchodilator response, atopic status, or use of inhaled corticosteroids.     

Aerosol Chemistry over a High Altitude Station at Northeastern Himalayas,India

Background

There is an urgent need for an improved understanding of the sources, distributions and properties of atmospheric aerosol in order to control the atmospheric pollution over northeastern Himalayas where rising anthropogenic interferences from rapid urbanization and development is becoming an increasing concern.

Methodology/Principal Findings

An extensive aerosol sampling program was conducted in Darjeeling (altitude ∼2200 meter above sea level (masl), latitude 27°01′N and longitude 88°15′E), a high altitude station in northeastern Himalayas, during January–December 2005. Samples were collected using a respirable dust sampler and a fine dust sampler simultaneously. Ion chromatograph was used to analyze the water soluble ionic species of aerosol. The average concentrations of fine and coarse mode aerosol were found to be 29.5±20.8 µg m⁻³ and 19.6±11.1 µg m⁻³ respectively. Fine mode aerosol dominated during dry seasons and coarse mode aerosol dominated during monsoon. Nitrate existed as NH₄NO₃ in fine mode aerosol during winter and as NaNO₃ in coarse mode aerosol during monsoon. Gas phase photochemical oxidation of SO₂ during premonsoon and aqueous phase oxidation during winter and postmonsoon were the major pathways for the formation of SO₄ ²⁻ in the atmosphere. Long range transport of dust aerosol from arid regions of western India was observed during premonsoon. The acidity of fine mode aerosol was higher in dry seasons compared to monsoon whereas the coarse mode acidity was higher in monsoon compared to dry seasons. Biomass burning, vehicular emissions and dust particles were the major types of aerosol from local and continental regions whereas sea salt particles were the major types of aerosol from marine source regions.

Conclusions/Significance

The year-long data presented in this paper provide substantial improvements to the heretofore poor knowledge regarding aerosol chemistry over northeastern Himalayas, and should be useful to policy makers in making control strategies.     

Influence of acid rain and liming on fluxes of NO and NO2 from forest soil

Flux measurements of nitric oxide (NO) and nitrogen dioxide (NO₂) were performed in a coniferous forest (Höglwald) in southern Germany using a fully automated measuring system based on the dynamic chamber method. The forest soil was predominately a source of NO, but mean flux rates of NO ranged from –26.3 (deposition) to 55 g N m^-2 h_-1 (emission). NO₂ was deposited on the forest soil with mean flux rates ranging from –4 to –72 g N m^-2 h_-1 . Removal of forest floor vegetation did not influence NO or NO₂ fluxes. Apparently, forest floor vegetation was neither a source of NO nor a significant sink of NO₂. When the organic layer of the forest soil was removed, net NO flux changed from emission to deposition. Thus NO emitted to the atmosphere was produced almost exclusively in the organic layer of the forest soil. Liming caused a significant decrease in the rate of NO emission by 43 to 100%, whereas irrigation with simulated acid rain increased the emission of NO by a factor of 3.1. Irrigation with simulated normal rain decreased the emission of NO by 35 to 100%. No such effects could be detected for the deposition of NO₂.     

Distinct Kinin-Induced Functions Are Altered in Circulating Cells of Young Type 1 Diabetic Patients

Aims/Hypothesis

We aimed to understand early alterations in kinin-mediated migration of circulating angio-supportive cells and dysfunction of kinin-sensitive cells in type-1 diabetic (T1D) patients before the onset of cardiovascular disease.

Methods

Total mononuclear cells (MNC) were isolated from peripheral blood of 28 T1D patients free from cardiovascular complications except mild background retinopathy (age: 34.8±1.6 years, HbA_1C: 7.9±0.2%) and 28 age- and sex-matched non-diabetic controls (H). We tested expression of kinin receptors by flow cytometry and migratory capacity of circulating monocytes and progenitor cells towards bradykinin (BK) in transwell migration assays. MNC migrating towards BK (BK^mig) were assessed for capacity to support endothelial cell function in a matrigel assay, as well as generation of nitric oxide (NO) and superoxide (O₂ ⁻*) by using the fluorescent probes diaminofluorescein and dihydroethidium.

Results

CD14^hiCD16^neg, CD14^hiCD16^pos and CD14^loCD16^pos monocytes and circulating CD34^pos progenitor cells did not differ between T1D and H subjects in their kinin receptor expression and migration towards BK. T1D BK^mig failed to generate NO upon BK stimulation and supported endothelial cell network formation less efficiently than H BK^mig. In contrast, O₂ ⁻* production was similar between groups. High glucose disturbed BK-induced NO generation by MNC-derived cultured angiogenic cells.

Conclusions/Interpretation

Our data point out alterations in kinin-mediated functions of circulating MNC from T1D patients, occurring before manifest macrovascular damage or progressed microvascular disease. Functional defects of MNC recruited to the vessel wall might compromise endothelial maintenance, initially without actively promoting endothelial damage, but rather by lacking supportive contribution to endothelial regeneration and healing.     

Association between Air Pollution and General Outpatient Clinic Consultations for Upper Respiratory Tract Infections in Hong Kong

Background and Objectives

Many studies have shown the adverse effects of air pollution on respiratory health, but few have examined the effects of air pollution on service utilisation in the primary care setting. The aim of this study was to examine the association between air pollution and the daily number of consultations due to upper respiratory tract infections (URTIs) in general outpatient clinics (GOPCs) in Hong Kong.

Methods

Daily data on the numbers of consultations due to URTIs in GOPCs, the concentrations of major air pollutants, and the mean values of metrological variables were retrospectively collected over a 3-year period (2008–2010, inclusive). Generalised additive models were constructed to examine the association between air pollution and the daily number of consultations, and to derive the relative risks and 95% confidence intervals (95% CI) of GOPC consultations for a unit increase in the concentrations of air pollutants.

Results

The mean daily consultations due to URTIs in GOPCs ranged from 68.4 to 253.0 over the study period. The summary relative risks (and 95% CI) of daily consultations in all GOPCs for the air pollutants PM₁₀, NO₂, O₃, and SO₂ were 1.005 (1.002, 1.009), 1.010 (1.006, 1.013), 1.009 (1.006, 1.012), and 1.004 (1.000, 1.008) respectively, per 10 µg/m³ increase in the concentration of each pollutant.

Conclusion

Significant associations were found between the daily number of consultations due to URTIs in GOPCs and the concentrations of air pollutants, implying that air pollution incurs a substantial morbidity and increases the burden of primary health care services.     

Increased Risk of Dementia in Patients Exposed to Nitrogen Dioxide and Carbon Monoxide: A Population-Based Retrospective Cohort Study

Background

The air pollution caused by vehicular emissions is associated with cognitive decline. However, the associations between the levels of nitrogen dioxide (NO₂) and carbon monoxide (CO) exposure and dementia remain poorly defined and have been addressed in only a few previous studies.

Materials and Methods

In this study, we obtained data on 29547 people from the National Health Insurance Research Database (NHIRD) of Taiwan, including data on 1720 patients diagnosed with dementia between 2000 and 2010, and we evaluated the risk of dementia among four levels of air pollutant. Detailed data on daily air pollution were available from January 1, 1998 to December 31, 2010. Yearly average concentrations of pollutants were calculated from the baseline to the date of dementia occurrence, withdrawal of patients, or the end of the study, and these data were categorized into quartiles, with Q1 being the lowest level and Q4 being the highest.

Results

In the case of NO₂, the adjusted hazard ratios (HRs) of dementia for all participants in Q2, Q3, and Q4 compared to Q1 were 1.10 (95% confidence interval (CI), 0.96–1.26), 1.01 (95% CI, 0.87–1.17), and 1.54 (95% CI, 1.34–1.77), and in the case of CO, the adjusted HRs were 1.07 (95% CI, 0.92–1.25), 1.37 (95% CI, 1.19–1.58), and 1.61 (95% CI, 1.39–1.85).

Conclusion

The results of this large retrospective, population-based study indicate that exposure to NO₂ and CO is associated with an increased risk of dementia in the Taiwanese population.     

Increase of nitrosative stress in patients with eosinophilic pneumonia

Background

Exhaled nitric oxide (NO) production is increased in asthma and reflects the degree of airway inflammation. The alveolar NO concentration (Calv) in interstitial pneumonia is reported to be increased. However, it remains unknown whether NO production is increased and nitrosative stress occurs in eosinophilic pneumonia (EP). We hypothesized that nitrosative stress markers including Calv, inducible type of NO synthase (iNOS), and 3-nitrotyrosine (3-NT), are upregulated in EP.

Methods

Exhaled NO including fractional exhaled NO (FE_NO) and Calv was measured in ten healthy subjects, 13 patients with idiopathic pulmonary fibrosis (IPF), and 13 patients with EP. iNOS expression and 3-NT formation were assessed by immunocytochemistory in BALf cells. The exhaled NO, lung function, and systemic inflammatory markers of the EP patients were investigated after corticosteroid treatment for 4 weeks.

Results

The Calv levels in the EP group (14.4 ± 2.0 ppb) were significantly higher than those in the healthy subjects (5.1 ± 0.6 ppb, p < 0.01) and the IPF groups (6.3 ± 0.6 ppb, p < 0.01) as well as the FE_NO and the corrected Calv levels (all p < 0.01). More iNOS and 3-NT positive cells were observed in the EP group compared to the healthy subject and IPF patient. The Calv levels had significant positive correlations with both iNOS (r = 0.858, p < 0.05) and 3-NT positive cells (r = 0.924, p < 0.01). Corticosteroid treatment significantly reduced both the FE_NO (p < 0.05) and the Calv levels (p < 0.01). The magnitude of reduction in the Calv levels had a significant positive correlation with the peripheral blood eosinophil counts (r = 0.802, p < 0.05).

Conclusions

These results suggested that excessive nitrosative stress occurred in EP and that Calv could be a marker of the disease activity.     

The Health Effects of a Forest Environment on Subclinical Cardiovascular Disease and Heath-Related Quality of Life

Background

Assessment of health effects of a forest environment is an important emerging area of public health and environmental sciences.

Purpose

To demonstrate the long-term health effects of living in a forest environment on subclinical cardiovascular diseases (CVDs) and health-related quality of life (HRQOL) compared with that in an urban environment.

Materials and Methods

This study included the detailed health examination and questionnaire assessment of 107 forest staff members (FSM) and 114 urban staff members (USM) to investigate the long-term health effects of a forest environment. Air quality monitoring between the forest and urban environments was compared. In addition, work-related factors and HRQOL were evaluated.

Results

Levels of total cholesterol, low-density lipoprotein cholesterol, and fasting glucose in the USM group were significantly higher than those in the FSM group. Furthermore, a significantly higher intima-media thickness of the internal carotid artery was found in the USM group compared with that in the FSM group. Concentrations of air pollutants, such as NO, NO₂, NO_x, SO₂, CO, PM_2.5, and PM₁₀ in the forest environment were significantly lower compared with those in the outdoor urban environment. Working hours were longer in the FSM group; however, the work stress evaluation as assessed by the job content questionnaire revealed no significant differences between FSM and USM. HRQOL evaluated by the World Health Organization Quality of Life-BREF questionnaire showed FSM had better HRQOL scores in the physical health domain.

Conclusions

This study provides evidence of the potential beneficial effects of forest environments on CVDs and HRQOL.     

Nitric oxide compounds have different effects profiles on human articular chondrocyte metabolism

Introduction

The pathogenesis of osteoarthritis (OA) is characterized by the production of high amounts of nitric oxide (NO), as a consequence of up-regulation of chondrocyte-inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines. NO donors represent a powerful tool for studying the role of NO in the cartilage in vitro. There is no consensus about NO effects on articular cartilage in part because the differences between the NO donors available. The aim of this work is to compare the metabolic profile of traditional and new generation NO donors to see which one points out the osteoarthritic process in the best way.

Methods

Human healthy and OA chondrocytes were isolated from patients undergoing joint replacement surgery, and primary cultured. Cells were stimulated with NO donors (NOC-12 or SNP). NO production was evaluated by the Griess method, and apoptosis was quantified by flow cytometry. Mitochondrial function was evaluated by analysing respiratory chain enzyme complexes, citrate synthase (CS) activities by enzymatic assay, mitochondrial membrane potential (Δψm) by JC-1 using flow cytometry, and ATP levels were measured by luminescence assays. Glucose transport was measured as the uptake of 2-deoxy-[³H]glucose (2-[³H]DG). Statistical analysis was performed using the Mann-Whitney U test.

Results

NOC-12 liberates approximately ten times more NO₂^- than SNP, but the level of cell death induced was not as profound as that produced by SNP. Normal articular chondrocytes stimulated with NOC-12 had reduced activity from complexes I, III y IV, and the mitochondrial mass was increased in these cells. Deleterious effects on ΔΨm and ATP levels were more profound with SNP, and this NO donor was able to reduce 2-[³H]DG levels. Both NO donors had opposite effects on lactate release, SNP diminished the levels and NOC-12 lead to lactate accumulation. OA chondrocytes incorporate significantly more 2-[³H]DG than healthy cells.

Conclusions

These findings suggest that the new generation donors, specifically NOC-12, mimic the OA metabolic process much better than SNP. Previous results using SNP have to be considered prudently since most of the effects observed can be induced by the interactions of secondary products of NO.