BackgroundFine particulate matter (FPM) in ambient air causes premature mortality due to cardiac disease in susceptible populations.ObjectiveOur objective in this study was to determine the most influential FPM components.MethodsA mouse model of atherosclerosis (ApoE−/−) was exposed to either filtered air or concentrated FPM (CAPs) in Tuxedo, New York (85 μg/m3 average, 6 hr/day, 5 days/week, for 6 months), and the FPM elemental composition was determined for each day. We also examined associations between PM components and mortality for two population studies: National Mortality and Morbidity Air Pollution Study (NMMAPS) and Hong Kong.ResultsFor the CAPs-exposed mice, the average of nickel was 43 ng/m3, but on 14 days, there were Ni peaks at ~ 175 ng/m3 and unusually low FPM and vanadium. For those days, back-trajectory analyses identified a remote Ni point source. Electrocardiographic measurements on CAPs-exposed and sham-exposed mice showed Ni to be significantly associated with acute changes in heart rate and its variability. In NMMAPS, daily mortality rates in the 60 cities with recent speciation data were significantly associated with average Ni and V, but not with other measured species. Also, the Hong Kong sulfur intervention produced sharp drops in sulfur dioxide, Ni, and V, but not other components, corresponding to the intervention-related reduction in cardiovascular and pulmonary mortality.ConclusionsKnown biological mechanisms cannot account for the significant associations between Ni with the acute cardiac function changes in the mice or with cardiovascular mortality in people at low ambient air concentrations; therefore, further research is needed.

Objective-Fine particulate matter Ͻ2.5 m (PM 2.5 ) has been implicated in vasoconstriction and potentiation of hypertension in humans. We investigated the effects of short-term exposure to PM 2.5 in the angiotensin II (AII) infusion model. Methods and Results-Sprague-Dawley rats were exposed to PM 2.5 or filtered air (FA) for 10 weeks. At week 9, minipumps containing AII were implanted and the responses studied over a week. Mean concentration of PM 2.5 inside the chamber was 79.1Ϯ7.4 g/m 3 . After AII infusion, mean arterial pressure was significantly higher in PM 2.5 -AII versus FA-AII group. Aortic vasoconstriction to phenylephrine was potentiated with exaggerated relaxation to the Rho-kinase (ROCK) inhibitor Y-27632 and increase in ROCK-1 mRNA levels in the PM 2.5 -AII group. Superoxide (O 2 ⅐ Ϫ ) production in aorta was increased in the PM 2.5 -AII compared to the FA group, inhibitable by apocynin and L-NAME with coordinate upregulation of NAD(P)H oxidase subunits p22 phox and p47 phox and depletion of tetrahydrobiopterin. In vitro exposure to ultrafine particles (UFP) and PM 2.5 was associated with an increase in ROCK activity, phosphorylation of myosin light chain, and myosin phosphatase target subunit (MYPT1). Pretreatment with the nonspecific antioxidant N-Acetylcysteine and the Rho kinase inhibitors (Fasudil and Y-27632) prevented MLC and MYPT-1 phosphorylation by UFP suggesting a O 2 ⅐Ϫ -mediated mechanism for PM 2.5 and UFP effects. Conclusions-Short-term air pollution exaggerates hypertension through O 2⅐Ϫ -mediated upregulation of the Rho/ROCK pathway. Key Words: air pollution Ⅲ NADPH oxidase Ⅲ hypertension Ⅲ free radicals Ⅲ Rho/ROCK F ine particulate matter (aerodynamic diameter Ͻ2.5 m, PM 2.5 ) in ambient air has been implicated in the pathogenesis of cardiovascular disease. [1][2][3] Recent studies have suggested that this risk is rapid and occurs within hours to days of exposure to high levels of PM 2.5 . 4 -6 Increases in blood pressure may represent an important mechanism through which PM 2.5 may modulate its effects. Data from recent epidemiological studies from North America and Europe are indeed consistent with this hypothesis and have associated short-term exposure to PM 2.5 with elevations in blood pressure (BP). 7,8 This effect seems to be exaggerated in predisposed individuals, 9 an observation that has also been noted in relation to the association of PM 2.5 with other chronic conditions such as atherosclerosis. 3,6,10 Although the precise mechanisms through which PM 2.5 gains access to the systemic vasculature is still hotly debated, there is increasing evidence that particles in the fine and ultrafine range transgress into the systemic circulation and modulate vascular tone acutely, presumably through reactive oxygen species (ROS)-dependent pathways. 11,12 We hypothesized that short-term (weeks) increases in PM 2.5 levels is associated with an increases in BP and that these responses are exaggerated in a model of angiotensin II (AII)-dependent hypertension through upregulation ...

ABSTRACT:The miscibility and crystallization behavior of two binary blends, poly(L-lactide) (PLLA)/poly(ethylene glycol) (PEG) and PLLA/poly(e-caprolactone) (PCL), with PLLA as the main component (PLLA composition was not lower than 50wt%) have been investigated by differential scanning calorimetry (DSC) and optical microscopy. PEG and PCL with moderate molecular weight (MW"" 10000) were used as the blending components for PLLA. PLLA and PEG were miscible in the melt over the composition range investigated. The variation of the bulk crystallization rate of PLLA with PEG composition displayed a maximum at IO wt% PEG. On the other hand, a monotonic increase in spherulite growth rate with increasing PEG composition was observed. Since the bulk crystallization rate is determined by both the nucleation density and the growth rate, the depression of nucleation density coupled with the increase of growth rate with increasing PEG composition may give rise to the observed maximum in the composition variation of the bulk crystallization rate. The crystallizability of PLLA and PEG in the blends was also evaluated. The crystallizability of PEG was reduced by blending with PLLA, while that of PLLA was essentially unaffected by blending with PEG. For the PLLA/PCL system, a phase-separated morphology was identified in the melt. However, the crystallization rate of PLLA could be enhanced upon blending with PCL. Since no preferential nucleation at the domain interface was observed, the promotion of PLLA crystallization rate was attributed to its partial miscibility with PCL.KEY WORDS Poly(L-lactide) / Poly(ethylene glycol) / Poly(e-caprolactone) / Blends / Miscibility / Crystallization Behavior / Biodegradable polymers have attracted increasing attention due to their potential applications as biomedical and environment-friendly materials. In addition to mechanical and thermal properties, the rate and extent of degradation are the essential considerations for biodegradable polymers. The degradation behavior of biodegradable polymers has been frequently controlled by modifying the chemical or stereochemical compositions of the polymers. 1 -5 Copolymerization, for example, is a popular method for such a modification, 1 • 2 • 5 Besides the chemical nature, the morphology of a biodegradable polymer may also be an influential factor on its degradation behavior. For example, when a semicrystalline biodegradable polymer is subjected to a degradation medium such as water and enzyme, the molecules of the medium would enter into the amorphous regions more easily than into the crystalline regions. The degradation rate will then depend on the degree of crystallinity and the chain packing in the amorphous regions, which are determined by the thermal history and the molecular weight. Therefore, morphological controls through thermal history and molecular weight variations, physical aging, and chain orientation may also be useful for controlling the degradation behavior of a biodegradable polymer. crystallizability and the morphology of biodegr...

Poly(ε-caprolactone) (PCL) with a wide range of molecular weight (MW) has been prepared via fractionation by either precipitating PCL/chloroform solutions into different amounts of methanol or adding methanol into PCL/tetrahydrofuran (THF) solutions. The samples with M n ranging from 1900 to 64 700 were used to investigate the MW effects on the spherulite growth rate, nucleation density, and equilibrium melting point (T m 0) of PCL. The variation of spherulite growth rate with MW exhibited a maximum rather than a conventional monotonic drop. The existence of such a maximum was rationalized by considering the interplay between the effects of MW on T m 0 and segmental mobility. A growth kinetic formula proposed by Hoffman was employed to extract the crystal surface free energy product (σσe). In contrast to the conventional Lauritzen−Hoffman analysis which was based on the growth rates measured at different crystallization temperatures (T c) for a given MW, the present analysis was based on the growth rates measured for different MW at a given T c. The spherulite nucleation density was found to be higher for the sample with larger MW, and this observation was interpreted based on the individual effects of MW on the primary nucleation rate and spherulite growth rate. An increase in MW promoted the nucleation rate much more significantly compared with its effect on the growth rate, and this in turn led to a higher nucleation density. An unusual morphology due to the segregation of uncrystallizable short chains into the interfibrillar regions of the spherulites was also observed for PCL with M n = 1900.

Radiation effects on cancer risks in a cohort of Taiwanese residents who received protracted low-dose-rate gamma-radiation exposures from (60)Co-contaminated reinforcing steel used to build their apartments were studied, and risks were compared to those in other radiation-exposed cohorts. Analyses were based on a more extended follow-up of the cohort population in which 117 cancer cases diagnosed between 1983 and 2005 among 6,242 people with an average excess cumulative exposure estimate of about 48 mGy. Cases were identified from Taiwan's National Cancer Registry. Radiation effects on cancer risk were estimated using proportional hazards models and were summarized in terms of the hazard ratio associated with a 100-mGy increase in dose (HR(100mGy)). A significant radiation risk was observed for leukemia excluding chronic lymphocytic leukemia (HR(100mGy) 1.19, 90% CI 1.01-1.31). Breast cancer exhibited a marginally significant dose response (HR(100mGy) 1.12, 90% CI 0.99-1.21). The results further strengthen the association between protracted low-dose radiation and cancer risks, especially for breast cancers and leukemia, in this unique cohort population.

Long-term exposure to fine particulate air pollution (PM2.5) has been associated increased risk of death from cardiopulmonary diseases. Cardiac function parameters have also been affected by ambient particulate matter (PM) exposure, including heart-rate variability (HRV), a measure of autonomic function that has been recognized as a well-defined, quantitative indicator of autonomic dysfunction. However, the role of HRV in ambient PM-induced cardiovascular effect is not fully understood. In an accompanying article, we report significant decreasing patterns of heart rate (HR), body temperature, and physical activity for mice lacking apoliproprotein (ApoE-/-) over 5 mo of exposure to concentrated ambient PM (CAPs), with smaller and nonsignificant change for C57 mice. In this article, we report the effects of subchronic CAPs exposure on HRV parameters that are sensitive to cardiac sympathetic and parasympathetic nerve activity. The standard deviation of normal to normal beat intervals (SDNN) and the square root of the mean squared differences of successive RR intervals (RMSSD) in the late afternoon and overnight for the ApoE-/- mice showed a gradual increase for the first 6 wk, a decline for about 12 more wk, and a slight turn upward at the end of the study period. For C57 mice, there were no chronic effect changes of SDNN or RMSSD in the late afternoon, an a slight increase after 6 wk for the overnight period. The response patterns of ApoE-/- mice indicated a perturbation of the homeostatic function in the cardiovascular system (initial enhancement and late depression of the HRV parameters). Our results complement the findings in human panel and controlled CAPs exposure studies in demonstrating that increased levels of particle pollution are able to perturb cardiac autonomic function, which may lead to adverse cardiovascular outcomes.

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