Impact of agglomeration state of nano- and submicron sized gold particles on pulmonary inflammation

Background

Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.

Objectives

To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.

Methods

In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 μg/m³) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.

Measurements and Main Results

Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).

Conclusion

Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.     

Beneficial cardiovascular effects of reducing exposure to particulate air pollution with a simple facemask

Background

Exposure to air pollution is an important risk factor for cardiovascular morbidity and mortality, and is associated with increased blood pressure, reduced heart rate variability, endothelial dysfunction and myocardial ischaemia. Our objectives were to assess the cardiovascular effects of reducing air pollution exposure by wearing a facemask.

Methods

In an open-label cross-over randomised controlled trial, 15 healthy volunteers (median age 28 years) walked on a predefined city centre route in Beijing in the presence and absence of a highly efficient facemask. Personal exposure to ambient air pollution and exercise was assessed continuously using portable real-time monitors and global positional system tracking respectively. Cardiovascular effects were assessed by continuous 12-lead electrocardiographic and ambulatory blood pressure monitoring.

Results

Ambient exposure (PM_2.5 86 ± 61 vs 140 ± 113 μg/m³; particle number 2.4 ± 0.4 vs 2.3 ± 0.4 × 10⁴ particles/cm³), temperature (29 ± 1 vs 28 ± 3°C) and relative humidity (63 ± 10 vs 64 ± 19%) were similar (P > 0.05 for all) on both study days. During the 2-hour city walk, systolic blood pressure was lower (114 ± 10 vs 121 ± 11 mmHg, P < 0.01) when subjects wore a facemask, although heart rate was similar (91 ± 11 vs 88 ± 11/min; P > 0.05). Over the 24-hour period heart rate variability increased (SDNN 65.6 ± 11.5 vs 61.2 ± 11.4 ms, P < 0.05; LF-power 919 ± 352 vs 816 ± 340 ms², P < 0.05) when subjects wore the facemask.

Conclusion

Wearing a facemask appears to abrogate the adverse effects of air pollution on blood pressure and heart rate variability. This simple intervention has the potential to protect susceptible individuals and prevent cardiovascular events in cities with high concentrations of ambient air pollution.     

Sustained Increase in Serum Glial Fibrillary Acidic Protein after First ST-Elevation Myocardial Infarction

Acute ischemic cardiac injury predisposes one to cognitive impairment, dementia, and depression. Pathophysiologically, recent positron emission tomography data suggest astroglial activation after experimental myocardial infarction (MI). We analyzed peripheral surrogate markers of glial (and neuronal) damage serially within 12 months after the first ST-elevation MI (STEMI). Serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were quantified using ultra-sensitive molecular immunoassays. Sufficient biomaterial was available from 45 STEMI patients (aged 28 to 78 years, median 56 years, 11% female). The median (quartiles) of GFAP was 63.8 (47.0, 89.9) pg/mL and of NfL 10.6 (7.2, 14.8) pg/mL at study entry 0–4 days after STEMI. GFAP after STEMI increased in the first 3 months, with a median change of +7.8 (0.4, 19.4) pg/mL (p = 0.007). It remained elevated without further relevant increases after 6 months (+11.7 (0.6, 23.5) pg/mL; p = 0.015), and 12 months (+10.3 (1.5, 22.7) pg/mL; p = 0.010) compared to the baseline. Larger relative infarction size was associated with a higher increase in GFAP (ρ = 0.41; p = 0.009). In contrast, NfL remained unaltered in the course of one year. Our findings support the idea of central nervous system involvement after MI, with GFAP as a potential peripheral biomarker of chronic glial damage as one pathophysiologic pathway.     

Experimental determination of the respiratory tract deposition of diesel combustion particles in patients with chronic obstructive pulmonary disease

Background

Air pollution, mainly from combustion, is one of the leading global health risk factors. A susceptible group is the more than 200 million people worldwide suffering from chronic obstructive pulmonary disease (COPD). There are few data on lung deposition of airborne particles in patients with COPD and none for combustion particles.

Objectives

To determine respiratory tract deposition of diesel combustion particles in patients with COPD during spontaneous breathing.

Methods

Ten COPD patients and seven healthy subjects inhaled diesel exhaust particles generated during idling and transient driving in an exposure chamber. The respiratory tract deposition of the particles was measured in the size range 10?C500?nm during spontaneous breathing.

Results

The deposited dose rate increased with increasing severity of the disease. However, the deposition probability of the ultrafine combustion particles (< 100?nm) was decreased in COPD patients. The deposition probability was associated with both breathing parameters and lung function, but could be predicted only based on lung function.

Conclusions

The higher deposited dose rate of inhaled air pollution particles in COPD patients may be one of the factors contributing to their increased vulnerability. The strong correlations between lung function and particle deposition, especially in the size range of 20?C30?nm, suggest that altered particle deposition could be used as an indicator respiratory disease.     

Myocardial Infarction Changes Sphingolipid Metabolism in the Uninfarcted Ventricular Wall of the Rat

It is known that the ratio, the level of sphingosine-1-phosphate (S1P)/the level of ceramide (CER) determines survival of the cells. The aim of the present study was to examine the effect of myocardial infarction on the level of different sphingolipids in the uninfarcted area. The experiments were carried out on male Wistar rats: 1, control; 2, after ligation of the left coronary artery (infarct) and 3, sham operated. Samples of the uninfarcted area of the left ventricle were taken in 1, 6 and 24 h after the surgery. The level of sphingolipids, S1P, CER, sphingosine (SPH), sphinganine-1-phosphate (SPA1P) and sphinganine (SPA) was determined. The control values were (ng/mg), S1P-0.33 ± 0.03, SPH-1.02 ± 0.13, SPA1P-0.11 ± 0.01, SPA-0.28 ± 0.04, total CER-20.3 ± 1.8. In infarct, the level of S1P in the uninfarcted area was reduced by ~3 times in 1 and 6 h and decreased further in 24 h. The level of SPH decreased in 1 h and returned to the control thereafter. The total level of CER decreased in 6 h after the infarction. Sham surgery also produced changes in the level of certain sphingolipids. The ratio, the level of S1P/the level of CER was markedly reduced at each time point after the infarction. It is concluded that the reduction in the S1P/CER ratio could be responsible for increased apoptosis in the uninfarcted area after the myocardial infarction in the rat.     

Effects of particulate matter on inflammatory markers in the general adult population

Background

Particulate air pollution is associated with increased risk of cardiovascular disease and stroke. Although the precise mechanisms underlying this association are still unclear, the induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway.

Methods

We used baseline data from the CoLaus Study including 6183 adult participants residing in Lausanne, Switzerland. We analyzed the association of short-term exposure to PM₁₀ (on the day of examination visit) with continuous circulating serum levels of high-sensitive C-reactive protein (hs-CRP), interleukin 1-beta (IL-1??), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-??) by robust linear regressions, controlling for potential confounding factors and assessing effect modification.

Results

In adjusted analyses, for every 10???g/m³ elevation in PM₁₀, IL-1? increased by 0.034 (95?% confidence interval, 0.007-0.060) pg/mL, IL-6 by 0.036 (0.015-0.057) pg/mL, and TNF-?? by 0.024 (0.013-0.035) pg/mL, whereas no significant association was found with hs-CRP levels.

Conclusions

Short-term exposure to PM₁₀ was positively associated with higher levels of circulating IL-1?, IL-6 and TNF-?? in the adult general population. This positive association suggests a link between air pollution and cardiovascular risk, although further studies are needed to clarify the mechanistic pathway linking PM₁₀ to cardiovascular risk.     

Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: Results of GISSI-prevenzione trial

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarctions conducted in the framework of the Italian public health system. In GISSI-Prevenzione, patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA (1 g daily) but not vitamin E (300 mg daily), was beneficial for death and for combined death, nonfatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death.At variance with the orientation of a scientific scenario largely dominated by the “cholesterol-heart hypothesis”, GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction.As to the relevance and comparability of GISSI-Prevenzione results, up to 5.7 lives could be saved every 1000 patients with previous myocardial infarction treated with n-3 PUFA (1 g daily) per year. Such a result is comparable to that observed in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial, where 5.2 lives could be saved per 1000 hypercholesterolemic, coronary heart disease patients treated with pravastatin for 1 yr.The choice of a relatively low-dose regimen (1-g capsule daily) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits, and the pattern of effects seen in GISSI-Prevenzione (namely, reduction of overall mortality with no decrease in the rate of nonfatal myocardial infarction) all strongly suggest that n-3 PUFA treatment should be considered a recommended new component of secondary prevention. The importance of this combined/additive effect is further suggested by the analyses of the interplay between diet and n-3 PUFA: There is an interesting direct correlation between size of the effect and “correctness” of background diets. It can be anticipated that a conceptual barrier must be overcome: A “dietary drug” should be added to “dietary advice”, which remains fundamental to allow this statement to become true in clinical practice.     

Higher Alcohol Synthesis Using K-Doped CoRhMoS2/MWCNT Catalysts: Influence of Pelletization,Particle Size and Incorporation of Binders

In this study, alkalinized MWCNT supported MoS₂ catalysts have been doubly-promoted with Co and Rh. Catalysts were prepared by the conventional co-impregnation method and stabilized under argon atmosphere. Characterization of the oxidic samples by BET revealed that the mesoporosity of the pristine MWCNT support was not compromised after loading a combined total of 30 wt% metals (9 wt% K, 4.5 wt% Co, 1.5 wt% Rh, and 15 wt% Mo) on the support; however, a significant decrease in specific surface area was observed. Broad angle XRD analysis confirmed the homogenous dispersion of catalyst metals on the support. Two catalyst grain sizes were first investigated to elucidate the effect of particle size: a finely ground powder (88 μm) and a pelletized form (1,780 μm). Despite the total alcohol yield of 0.261 g/(g_cat h) observed by conducting higher alcohol synthesis reaction at T = 330 °C, P = 8.3 MPa, H₂/CO = 1.25, and GHSV = 3.6 m _STP ³ /(kg_cat h) for the fine powdered sample, the relatively higher pressure drop could be minimized by using the pelletized form of the catalyst. Finally, a systematic study of variety of selected binders was conducted to gain insight of catalyst’s applicability for industrial purposes. Three selected binders namely: bentonite clay, coal tar, and humic acid were thus investigated; taking into consideration significant factors such as melting point and binder requirement per catalyst support. The CO conversions evaluated for the two binder-free catalysts (88 and 1,700 μm) showed that the catalyst with fine particle sizes (88 μm) performed better than that in the pelletized form (binder-free, 1,700 μm); yielding a maximum ethanol selectivity of 38.5 % at steady-state reaction conditions.     

CLA Supplementation and Aerobic Exercise Lower Blood Triacylglycerol,but Have No Effect on Peak Oxygen Uptake or Cardiorespiratory Fatigue Thresholds

This study examined the effects of 6 weeks of conjugated linoleic acid (CLA) supplementation and moderate aerobic exercise on peak oxygen uptake ( \(\dot{V}{\text{O}}_{ 2}\) peak), the gas exchange threshold (GET), the respiratory compensation point (RCP), and serum concentrations of cholesterol, triacylglycerol, and glucose in humans. Thirty-four untrained to moderately trained men (mean ± SD; age = 21.5 ± 2.8 years; mass = 77.2 ± 9.5 kg) completed this double-blind, placebo controlled study and were randomly assigned to either a CLA (Clarinol A-80; n = 18) or placebo (PLA; sunflower oil; n = 16) group. Prior to and following 6 weeks of aerobic training (50 % \(\dot{V}{\text{O}}_{ 2}\) peak for 30 min, twice per week) and supplementation (5.63 g of total CLA isomers [of which 2.67 g was c9, t11 and 2.67 g was t10, c12] or 7.35 g high oleic sunflower oil per day), each participant completed an incremental cycle ergometer test to exhaustion to determine their \(\dot{V}{\text{O}}_{ 2}\) peak, GET, and RCP and fasted blood draws were performed to measure serum concentrations of cholesterol, triacylglycerol, and glucose. Serum triacylglycerol concentrations were lower (p < 0.05) in the CLA than the PLA group. For \(\dot{V}{\text{O}}_{ 2}\) peak and glucose, there were group × time interactions (p < 0.05), however, post hoc statistical tests did not reveal any differences (p > 0.05) between the CLA and PLA groups. GET and RCP increased (p < 0.05) from pre- to post-training for both the CLA and PLA groups. Overall, these data suggested that CLA and aerobic exercise may have synergistic, blood triacylglycerol lowering effects, although CLA may be ineffective for enhancing aerobic exercise performance in conjunction with a 6-week aerobic exercise training program in college-age men.     

A novel method to detect unlabeled inorganic nanoparticles and submicron particles in tissue by sedimentation field-flow fractionation

 

A novel methodology to detect unlabeled inorganic nanoparticles was experimentally demonstrated using a mixture of nano-sized (70 nm) and submicron (250 nm) silicon dioxide particles added to mammalian tissue. The size and concentration of environmentally relevant inorganic particles in a tissue sample can be determined by a procedure consisting of matrix digestion, particle recovery by centrifugation, size separation by sedimentation field-flow fractionation (SdFFF), and detection by light scattering.

Background

Laboratory nanoparticles that have been labeled by fluorescence, radioactivity, or rare elements have provided important information regarding nanoparticle uptake and translocation, but most nanomaterials that are commercially produced for industrial and consumer applications do not contain a specific label.

Methods

Both nitric acid digestion and enzyme digestion were tested with liver and lung tissue as well as with cultured cells. Tissue processing with a mixture of protease enzymes is preferred because it is applicable to a wide range of particle compositions. Samples were visualized via fluorescence microscopy and transmission electron microscopy to validate the SdFFF results. We describe in detail the tissue preparation procedures and discuss method sensitivity compared to reported levels of nanoparticles in vivo.

Conclusion

Tissue digestion and SdFFF complement existing techniques by precisely identifying unlabeled metal oxide nanoparticles and unambiguously distinguishing nanoparticles (diameter<100 nm) from both soluble compounds and from larger particles of the same nominal elemental composition. This is an exciting capability that can facilitate epidemiological and toxicological research on natural and manufactured nanomaterials.     

Preparation of highly flexible chitin nanofiber-graft-poly(γ-l-glutamic acid) network film

In the previous study, we successfully prepared a chitin nanofiber film by regeneration from a chitin ion gel with an ionic liquid using methanol. In this study, we performed surface-initiated graft polymerization of γ-benzyl l-glutamate N-carboxyanhydride (BLG-NCA) from amino groups on a partially deacetylated chitin nanofiber (PDA-CNF) film. First, the chitin nanofiber film was immersed in 40 % NaOH aq. at 80 °C for 7 h for partial deacetylation. Then, the PDA-CNF film was immersed in a solution of BLG-NCA in ethyl acetate at 0 °C for 24 h for graft polymerization from amino groups on nanofibers to give a chitin nanofiber-graft-poly(γ-benzyl l-glutamate) (CNF-g-PBLG) film. The analytical results of the film indicated that graft polymerization of BLG-NCA occur on surface of nanofibers. Furthermore, the film was treated with 1.0 mol/L NaOH aq. to convert PBLG on nanofibers into poly(γ-l-glutamic acid sodium salt) (PLGA). Then, condensation of the resulting carboxylates with amino groups at the terminal ends of PLGAs or the remaining amino groups on nanofibers was performed using the condensing agent to produce a CNF-g-PLGA network film. The resulting film showed the good mechanical properties with high flexibility, which has potentials as promising materials for practical applications.     

Intake of up to 3 Eggs/Day Increases HDL Cholesterol and Plasma Choline While Plasma Trimethylamine-<Emphasis Type="Italic">N</Emphasis>-oxide is Unchanged in a Healthy Population

Eggs are a source of cholesterol and choline and may impact plasma lipids and trimethylamine-N-oxide (TMAO) concentrations, which are biomarkers for cardiovascular disease (CVD) risk. Therefore, the effects of increasing egg intake (0, 1, 2, and 3 eggs/day) on these and other CVD risk biomarkers were evaluated in a young, healthy population. Thirty-eight subjects [19 men/19 women, 24.1 ± 2.2 years, body mass index (BMI) 24.3 ± 2.5 kg/m²] participated in this 14-week crossover intervention. Participants underwent a 2-week washout with no egg consumption, followed by intake of 1, 2, and 3 eggs/day for 4 weeks each. Anthropometric data, blood pressure (BP), dietary records, and plasma biomarkers (lipids, glucose, choline, and TMAO) were measured during each intervention phase. BMI, waist circumference, systolic BP, plasma glucose, and plasma triacylglycerol did not change throughout the intervention. Diastolic BP decreased with egg intake (P < 0.05). Compared to 0 eggs/day, intake of 1 egg/day increased HDL cholesterol (HDL-c) (P < 0.05), and decreased LDL cholesterol (LDL-c) (P < 0.05) and the LDL-c/HDL-c ratio (P < 0.01). With intake of 2–3 eggs/day, these changes were maintained. Plasma choline increased dose-dependently with egg intake (P < 0.0001) while fasting plasma TMAO was unchanged. These results indicate that in a healthy population, consuming up to 3 eggs/day results in an overall beneficial effect on biomarkers associated with CVD risk, as documented by increased HDL-c, a reduced LDL-c/HDL-c ratio, and increased plasma choline in combination with no change in plasma LDL-c or TMAO concentrations.     

Maternal fruit and vegetable or vitamin C consumption during pregnancy is associated with fetal growth and infant growth up to 6 months: results from the Korean Mothers and Children’s Environmental Health (MOCEH) cohort study

Background

Based on data obtained from pregnant women who participated in the Mothers and Children’s Environmental Health (MOCEH) study in South Korea, we aimed to determine whether maternal intake of fruits and vegetables or vitamin C is associated with fetal and infant growth.

Methods

A total of 1138 Korean pregnant women at 12–28 weeks gestation with their infants were recruited as study participants for the MOCEH. Intake of fruits and vegetables or vitamin C during pregnancy was assessed by a 1-day 24-h recall method. Fetal biometry was determined by ultrasonography at late pregnancy. Infant weight and length were measured at birth and 6 months.

Results

A multiple regression analysis after adjusting for covariates showed that maternal intake of fruits and vegetables was positively associated with the biparietal diameter of the fetus and infant’s weight from birth to 6 months. Also, maternal vitamin C intake was positively associated with the abdominal circumference of the fetus and infant birth length. In addition, there was a significant inverse relationship between consumption of fruits and vegetables (below the median compared to above the median of ≥519 g/d) and the risk of low growth (<25th percentile) of biparietal diameter (odds ratio (OR): 2.220; 95% confidence interval (CI): 1.153–4.274) and birth weight (OR: 1.434; 95% CI: 1.001–2.056). A significant inverse relationship also existed between vitamin C consumption (below vs above the estimated average requirement (EAR) of ≥85 mg/d) and the risk of low growth (<25th percentile) of birth weight (OR: 1.470; 95% CI: 1.011–2.139), weight from birth to 6 months (OR: 1.520; 95% CI: 1.066–2.165), and length at birth (OR: 1.579; 95% CI: 1.104–2.258).

Conclusions

An increased intake of fruits and vegetables or vitamin C at mid-pregnancy is associated with increased fetal growth and infant growth up to 6 months of age.

     

Effect of New Zealand blueberry consumption on recovery from eccentric exercise-induced muscle damage

Background

Exercise-induced muscle damage (EIMD) is accompanied by localized oxidative stress / inflammation which, in the short-term at least, is associated with impaired muscular performance. Dietary antioxidants have been shown to reduce excessive oxidative stress; however, their effectiveness in facilitating recovery following EIMD is not clear. Blueberries demonstrate antioxidant and anti-inflammatory properties. In this study we examine the effect of New Zealand blueberries on EIMD after strenuous eccentric exercise.

Methods

In a randomized cross-over design, 10 females consumed a blueberry smoothie or placebo of a similar antioxidant capacity 5 and 10 hours prior to and then immediately, 12 and 36 hours after EIMD induced by 300 strenuous eccentric contractions of the quadriceps. Absolute peak and average peak torque across the knee, during concentric, isometric, and eccentric actions were measured. Blood biomarkers of oxidative stress, antioxidant capacity, and inflammation were assessed at 12, 36 and 60 hours post exercise. Data were analyzed using a two-way ANOVA.

Results

A significant (p?p?=?0.047) interaction effect was seen for peak isometric tension suggesting a faster rate of recovery in the blueberry intervention group. A similar trend was observed for concentric and eccentric strength. An increase in oxidative stress and inflammatory biomarkers was also observed in both treatment groups following EIMD. Although a faster rate of decrease in oxidative stress was observed in the blueberry group, it was not significant (p?Conclusions This study demonstrates that the ingestion of a blueberry smoothie prior to and after EIMD accelerates recovery of muscle peak isometric strength. This effect, although independent of the beverage??s inherent antioxidant capacity, appears to involve an up-regulation of adaptive processes, i.e. endogenous antioxidant processes, activated by the combined actions of the eccentric exercise and blueberry consumption. These findings may benefit the sporting community who should consider dietary interventions that specifically target health and performance adaptation.     

Salivary Secretory Immunoglobulin a secretion increases after 4-weeks ingestion of chlorella-derived multicomponent supplement in humans: a randomized cross over study

Background

The relationship between fish intake and stroke incidence has been inconsistent in previous Swedish studies. Here, we report the risk of stroke and fish intake in a cohort from southern Sweden.

Findings

Data were obtained from an already available population based case-control study where the cases were defined as incident first-time ischemic stroke patients. Complete data on all relevant variables were obtained for 2722 controls and 2469 cases. The data were analyzed with logistic regression analysis. Stroke risk decreased with fat fish intake ([greater than or equal to] 1/week versus <1/month) in both men and women; adjusted pooled Odds Ratio (OR) 0.69, 95% Confidence Interval (CI): 0.54-0.89. However, stroke risk for women increased with intake of lean fish; adjusted OR 1.63 (95% CI: 1.17-2.28), whereas there was no association with men's lean fish intake; adjusted OR 0.97(95% CI: 0.73-1.27). Fish intake was self-reported retrospectively, yielding uncertain exposure assessment and potential recall bias. The findings regarding lean fish could be explained by recall bias if an individual's inclination to report lean fish consumption depended on both disease status and sex. The fact that the association between fat fish intake and stroke was similar in men and women does not support such a differential in recall.

Conclusions

The results suggest fat fish intake to decrease ischemic stroke risk and lean fish intake to increase women's stroke risk. The inconsistent relationship between fish intake and stroke risk reported in previous studies is further stressed by the results of this study.     

Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes

Background

Engineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNT (5 mg/m³, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation.

Results

Twenty-three percent of the filtered air controls, 26.5% of the MWCNT-exposed, and 51.9% of the MCA-exposed mice, had lung bronchiolo-alveolar adenomas and lung adenocarcinomas. The average number of tumors per mouse was 0.25, 0.81 and 0.38 respectively. By contrast, 90.5% of the mice which received MCA followed by MWCNT had bronchiolo-alveolar adenomas and adenocarcinomas with an average of 2.9 tumors per mouse 17months after exposure. Indeed, 62% of the mice exposed to MCA followed by MWCNT had bronchiolo-alveolar adenocarcinomas compared to 13% of the mice that received filtered air, 22% of the MCA-exposed, or 14% of the MWCNT-exposed. Mice with early morbidity resulting in euthanasia had the highest rate of metastatic disease. Three mice exposed to both MCA and MWCNT that were euthanized early had lung adenocarcinoma with evidence of metastasis (5.5%). Five mice (9%) exposed to MCA and MWCNT and 1 (1.6%) exposed to MCA developed serosal tumors morphologically consistent with sarcomatous mesotheliomas, whereas mice administered MWCNT or air alone did not develop similar neoplasms.

Conclusions

These data demonstrate that some MWCNT exposures promote the growth and neoplastic progression of initiated lung cells in B6C3F1 mice. In this study, the mouse MWCNT lung burden of 31.2 μg/mouse approximates feasible human occupational exposures. Therefore, the results of this study indicate that caution should be used to limit human exposures to MWCNT.     

Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways

Background

Exposure to fine ambient particulate matter (PM) has consistently been associated with increased morbidity and mortality. The relationship between exposure to ultrafine particles (UFP) and health effects is less firmly established. If UFP cause health effects independently from coarser fractions, this could affect health impact assessment of air pollution, which would possibly lead to alternative policy options to be considered to reduce the disease burden of PM. Therefore, we organized an expert elicitation workshop to assess the evidence for a causal relationship between exposure to UFP and health endpoints.

Methods

An expert elicitation on the health effects of ambient ultrafine particle exposure was carried out, focusing on: 1) the likelihood of causal relationships with key health endpoints, and 2) the likelihood of potential causal pathways for cardiac events. Based on a systematic peer-nomination procedure, fourteen European experts (epidemiologists, toxicologists and clinicians) were selected, of whom twelve attended. They were provided with a briefing book containing key literature. After a group discussion, individual expert judgments in the form of ratings of the likelihood of causal relationships and pathways were obtained using a confidence scheme adapted from the one used by the Intergovernmental Panel on Climate Change.

Results

The likelihood of an independent causal relationship between increased short-term UFP exposure and increased all-cause mortality, hospital admissions for cardiovascular and respiratory diseases, aggravation of asthma symptoms and lung function decrements was rated medium to high by most experts. The likelihood for long-term UFP exposure to be causally related to all cause mortality, cardiovascular and respiratory morbidity and lung cancer was rated slightly lower, mostly medium. The experts rated the likelihood of each of the six identified possible causal pathways separately. Out of these six, the highest likelihood was rated for the pathway involving respiratory inflammation and subsequent thrombotic effects.

Conclusion

The overall medium to high likelihood rating of causality of health effects of UFP exposure and the high likelihood rating of at least one of the proposed causal mechanisms explaining associations between UFP and cardiac events, stresses the importance of considering UFP in future health impact assessments of (transport-related) air pollution, and the need for further research on UFP exposure and health effects.     

A Strategy for Preparing Star Polymers Containing Metal–Metal Bonds Along the Polymeric Arms Using Click Chemistry

The [(η⁵-C₅H₄(CH₂)₃N₃)Mo(CO)₃]₂ dimer (3) was prepared and used to determine if the Huisgen cycloaddition reaction could be used to synthesize high molecular weight star polymers with metal–metal bonds in the arms. Several different click catalysts were examined. Cp*Ru(PPh₃)₂Cl (Cp* = η⁵-C₅(CH₃)₅) was previously shown to catalyze the formation of metal–metal bond-containing polymers using click chemistry; however, this catalyst underwent a Staudinger reaction with dimer 3 when a model coupling reaction was attempted with phenylacetylene. In order to avoid the Staudinger reaction, Cp*Ru(COD)Cl was used as the catalyst in the reaction of 3 with phenylacetylene, and coupling was observed after 14 h. Synthesis of a star polymer was attempted with 3 and 1,3,5-triethynylbenzene. Instead of coupling, Cp*Ru(COD)Cl reacted with the 1,3,5-triethynylbenzene. A third catalyst, Cu(IMes)Cl (IMes = 1,3-dimesityl-imidazol-2-ylidene) was used to couple 3 with 1,3,5-triethynylbenzene in 48 h. Both a high molecular weight polymer (M _n  = 77,000 g mol^?1) and a tripodal star core (M _n  = 1,800 g mol^?1) were successfully prepared with this catalyst.     

A living cell quartz crystal microbalance biosensor for continuous monitoring of cytotoxic responses of macrophages to single-walled carbon nanotubes

Background

There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease.

Methods

We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE ^-/-) mice exposed to TiO₂. ApoE ^-/- mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO₂ (fTiO₂, 288 nm), photocatalytic 92/8 anatase/rutile TiO₂ (pTiO₂, 12 nm), or rutile nano TiO₂ (nTiO₂, 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO₂ (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO₂-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs).

Results

The exposure to nTiO₂ was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE ^-/- mice exposed to fine and photocatalytic TiO₂ had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO₂.

Conclusion

Repeated exposure to nanosized TiO₂ particles was associated with modest plaque progression in ApoE ^-/- mice. There were no associations between the pulmonary TiO₂ exposure and inflammation or vasodilatory dysfunction.     

A Micro-manipulation Technique for the Purification of Diatoms for Isotope and Geochemical Analysis

A method is described for the purification and extraction of diatom samples for isotope and geochemical analysis. The technique involves a micro-manipulator attached to an inverted microscope with a cellular micro-injector system used to remove contaminants or separate assemblages into single-species samples. Whilst time consuming, the advances associated with this technique, eliminating issues related to contamination and the impact of species-dependent fractionation factor/isotopic effect, allows ultra-clean as well as species and/or size specific diatom samples to be analysed in palaeoenvironmental research down to seasonal timescale resolution. By further altering the inner dimensions of the commercially available capillary tubes, (3.5–150  $\upmu $ m) this technique can be extended for use with other microfossils including radiolaria (30  $\upmu $ m to 1 mm), pollen (6–100  $\upmu $ m) and phytolith samples (1–200  $\upmu $ m).