Functional characterization of the water-soluble organic carbon of size-fractionated aerosol in the southern Mississippi Valley

The chemical content of water-soluble organic carbon (WSOC) as a function of particle size was characterized in Little Rock, Arkansas in winter and spring 2013. The objectives of this study were to (i) compare the functional characteristics of coarse, fine and ultrafine WSOC and (ii) reconcile the sources of WSOC for periods when carbonaceous aerosol was the most abundant particulate component. The WSOC accounted for 5% of particle mass for particles with <i>d</i>_p > 0.96 μm and 10% of particle mass for particles with <i>d</i>_p < 0.96 μm. Non-exchangeable aliphatic (H–C), unsaturated aliphatic (H–C–C=), oxygenated saturated aliphatic (H–C–O), acetalic (O–CH–O) and aromatic (Ar–H) protons were determined by proton nuclear magnetic resonance (¹H-NMR). The total non-exchangeable organic hydrogen concentrations varied from 4.1 ± 0.1 nmol m⁻³ for particles with 1.5 < <i>d</i>_p < 3.0 μm to 73.9 ± 12.3 nmol m⁻³ for particles with <i>d</i>_p < 0.49 μm. The molar H / C ratios varied from 0.48 ± 0.05 to 0.92 ± 0.09, which were comparable to those observed for combustion-related organic aerosol. The R–H was the most abundant group, representing about 45% of measured total non-exchangeable organic hydrogen concentrations, followed by H–C–O (27%) and H–C–C= (26%). Levoglucosan, amines, ammonium and methanesulfonate were identified in NMR fingerprints of fine particles. Sucrose, fructose, glucose, formate and acetate were associated with coarse particles. These qualitative differences of ¹H-NMR profiles for different particle sizes indicated the possible contribution of biological aerosols and a mixture of aliphatic and oxygenated compounds from biomass burning and traffic exhausts. The concurrent presence of ammonium and amines also suggested the presence of ammonium/aminium nitrate and sulfate secondary aerosol. The size-dependent origin of WSOC was further corroborated by the increasing δ¹³C abundance from −26.81 ± 0.18&permil; for the smallest particles to −25.93 ± 0.31&permil; for the largest particles and the relative distribution of the functional groups as compared to those previously observed for marine, biomass burning and secondary organic aerosol. The latter also allowed for the differentiation of urban combustion-related aerosol and biological particles. The five types of organic hydrogen accounted for the majority of WSOC for particles with <i>d</i>_p > 3.0 μm and <i>d</i>_p < 0.96 μm

Cerebrospinal Fluid Secretory Ca2+-Dependent Phospholipase A2 Activity Is Increased in Alzheimer Disease

BACKGROUND: The phospholipase A(2) (PLA2) family comprises multiple isoenzymes that vary in their physicochemical properties, cellular localizations, calcium sensitivities, and substrate specificities. Despite these differences, PLA2s share the ability to catalyze the synthesis of the precursors of the proinflammatory mediators. To investigate the potential of PLA2 as a biomarker in screening neuroinflammatory disorders in both clinical and research settings, we developed a PLA2 assay and determined the predominant types of PLA2 activity in cerebrospinal fluid (CSF). METHODS: We used liposomes composed of a fluorescent probe (bis-Bodipy(®) FL C11-PC [1,2-bis-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-undecanoyl)-sn-glycero-3-phosphocholine]) and 1,2-dioleoyl-l-α-phosphatidylcholine as a substrate to measure CSF PLA2 activity in a 96-well microtiter plate format. We established the type of CSF PLA2 activity using type-specific inhibitors of PLA2. RESULTS: Using 5 μL CSF per assay, our PLA2 activity assay was reproducible with CVs <15% in 2 CSF samples and for recombinant secretory Ca(2+)-dependent PLA2 (sPLA2) in concentrations ranging from 0.25 to 1 μmol/L. This PLA2 assay allowed identification of sPLA2 activity in lumbar CSF from healthy individuals 20–77 years old that did not depend on either sex or age. Additionally, CSF sPLA2 activity was found to be increased (P = 0.0008) in patients with Alzheimer disease. CONCLUSIONS: Adult human CSF has sPLA2 activity that can be measured reliably with the assay described. This enzyme activity in the CSF is independent of both sex and age and might serve as a valuable biomarker of neuroinflammation, as we demonstrated in Alzheimer disease

Molecular Speciation of Size Fractionated Particulate Water-Soluble Organic Carbon by Two-Dimensional Nuclear Magnetic Resonance (NMR) Spectroscopy

Particulate matter is associated with increased morbidity and mortality; its effects depend on particle size and chemical content. It is important to understand the composition and resultant toxicological profile of particulate organic compounds, the largest and most complex fraction of particulate matter. The objective of the study was to delineate the nuclear magnetic resonance (NMR) spectral fingerprint of the biologically relevant water-soluble organic carbon (WSOC) fraction of size fractionated urban aerosol. A combination of one and two-dimensional NMR spectroscopy methods was used. The size distribution of particle mass, water-soluble extract, non-exchangeable organic hydrogen functional types and specific biomarkers such as levoglucosan, methane sulfonate, ammonium and saccharides indicated the contribution of fresh and aged wood burning emissions, anthropogenic and biogenic secondary aerosol for fine particles as well as primary traffic exhausts and pollen for large particles. Humic-like macromolecules in the fine particle size range included branched carbon structures containing aromatic, olefinic, keto and nitrile groups and terminal carboxylic and hydroxyl groups such as terpenoid-like polycarboxylic acids and polyols. Our study show that 2D-NMR spectroscopy can be applied to study the chemical composition of size fractionated aerosol

Comparative study of atmospheric water-soluble organic aerosols composition in contrasting suburban environments in the Iberian Peninsula Coast

This study investigates the structural composition and major sources of water-soluble organic matter (WSOM) from PM2.5 collected, in parallel, during summer and winter, in two contrasting suburban sites at Iberian Peninsula Coast: Aveiro (Portugal) and Coruña (Spain). PM10 samples were also collected at Coruña for comparison. Ambient concentrations of PM2.5, total nitrogen (TN), and WSOM were higher in Aveiro than in Coruña, with the highest levels found in winter at both locations. In Coruña, concentrations of PM10, TN, and WSOM were higher than those from PM2.5. Regardless of the season, stable isotopic δ13C and δ15N in PM2.5 suggested important contributions of anthropogenic fresh organic aerosols (OAs) at Aveiro. In Coruña, δ13C and δ15N of PM2.5 and PM10 suggests decreased anthropogenic input during summer. Although excitation-emission fluorescence profiles were similar for all WSOM samples, multi-dimensional nuclear magnetic resonance (NMR) spectroscopy confirmed differences in their structural composition, reflecting differences in aging processes and/or local sources between the two locations. In PM2.5 WSOM in Aveiro, the relative distribution of non-exchangeable proton functional groups was in the order: H-C (40-43%) > H-C-C= (31-39%) > H-C-O (12-15%) > Ar-H (5.0-13%). However, in PM2.5 and PM10 WSOM in Coruña, the relative contribution of H-C-O groups (24-30% and 23-29%, respectively) equals and/or surpasses that of H-C-C= (25-26% and 25-29%, respectively), being also higher than those of Aveiro. In both locations, the highest aromatic contents were observed during winter due to biomass burning emissions. The structural composition of PM2.5 and PM10 WSOM in Coruña is dominated by oxygenated aliphatic compounds, reflecting the contribution of secondary OAs from biogenic, soil dust, and minor influence of anthropogenic emissions. In contrast, the composition of PM2.5 WSOM in Aveiro appears to be significantly impacted by fresh and secondary anthropogenic OAs. Marine and biomass burning OAs are important contributors, common to both sites.Xunta de Galicia ( Programa de Consolidación y Estructuración de Unidades de Investigación Competitivas Refs. GRC2013-047 and ED431C 2017/28)publishe

Hexose-6-phosphate Dehydrogenase Modulates 11β-Hydroxysteroid Dehydrogenase Type 1-Dependent Metabolism of 7-keto- and 7β-hydroxy-neurosteroids

BACKGROUND: The role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in the regulation of energy metabolism and immune system by locally reactivating glucocorticoids has been extensively studied. Experiments determining initial rates of enzyme activity revealed that 11beta-HSD1 can catalyze both the reductase and the dehydrogenase reaction in cell lysates, whereas it predominantly catalyzes the reduction of cortisone to cortisol in intact cells that also express hexose-6-phosphate dehydrogenase (H6PDH), which provides cofactor NADPH. Besides its role in glucocorticoid metabolism, there is evidence that 11beta-HSD1 is involved in the metabolism of 7-keto- and 7-hydroxy-steroids; however the impact of H6PDH on this alternative function of 11beta-HSD1 has not been assessed. METHODOLOGY: We investigated the 11beta-HSD1-dependent metabolism of the neurosteroids 7-keto-, 7alpha-hydroxy- and 7beta-hydroxy-dehydroepiandrosterone (DHEA) and 7-keto- and 7beta-hydroxy-pregnenolone, respectively, in the absence or presence of H6PDH in intact cells. 3D-structural modeling was applied to study the binding of ligands in 11beta-HSD1. PRINCIPAL FINDINGS: We demonstrated that 11beta-HSD1 functions in a reversible way and efficiently catalyzed the interconversion of these 7-keto- and 7-hydroxy-neurosteroids in intact cells. In the presence of H6PDH, 11beta-HSD1 predominantly converted 7-keto-DHEA and 7-ketopregnenolone into their corresponding 7beta-hydroxy metabolites, indicating a role for H6PDH and 11beta-HSD1 in the local generation of 7beta-hydroxy-neurosteroids. 3D-structural modeling offered an explanation for the preferred formation of 7beta-hydroxy-neurosteroids. CONCLUSIONS: Our results from experiments determining the steady state concentrations of glucocorticoids or 7-oxygenated neurosteroids suggested that the equilibrium between cortisone and cortisol and between 7-keto- and 7-hydroxy-neurosteroids is regulated by 11beta-HSD1 and greatly depends on the coexpression with H6PDH. Thus, the impact of H6PDH on 11beta-HSD1 activity has to be considered for understanding both glucocorticoid and neurosteroid action in different tissues

Arachidonic acid pathway alterations in cerebrospinal fluid of dogs with naturally occurring spinal cord injury

BACKGROUND: Canine intervertebral disc πherniation causes a naturally-occurring spinal cord injury (SCI) that bears critical similarities to human SCI with respect to both injury pathomechanisms and treatment. As such, it has tremendous potential to enhance our understanding of injury biology and the preclinical evaluation of novel therapies. Currently, there is limited understanding of the role of arachidonic acid metabolites in canine SCI. RESULTS: The CSF concentrations of PLA2 and PGE2 were higher in SCI dogs compared to control dogs (p = 0.0370 and 0.0273, respectively), but CSF LCT4 concentration in SCI dogs was significantly lower than that in control dogs (p < 0.0001). Prostaglandin E2 concentration in the CSF was significantly and positively associated with increased severity of SCI at the time of sampling (p = 0.041) and recovery 42 days post-injury (p = 0.006), as measured by ordinal behavioral scores. CONCLUSION: Arachidonic acid metabolism is altered in dogs with SCI, and these data suggest that these AA metabolites reflect injury severity and recovery, paralleling data from other model systems

Trends of Non-Accidental, Cardiovascular, Stroke and Lung Cancer Mortality in Arkansas Are Associated with Ambient PM2.5 Reductions

The cardiovascular and stroke mortality rates in Arkansas are among the highest in the USA. The annual trends of stroke and cardiovascular mortality are barely correlated to smoking cessation; while the prevalence of risk factors such as obesity; cholesterol and hypertension increased over the 1979–2007 period. The study determined the effect of chronic exposure to PM2.5 on non-accidental; cardiovascular; stroke and lung cancer mortality in Arkansas over the 2000–2010 period using the World Health Organization’s log-linear health impact model. County chronic exposures to PM2.5 were computed by averaging spatially-resolved gridded concentrations using PM2.5 observations. A spatial uniformity was observed for PM2.5 mass levels indicating that chronic exposures were comparable throughout the state. The reduction of PM2.5 mass levels by 3.0 μg/m3 between 2000 and 2010 explained a significant fraction of the declining mortality. The effect was more pronounced in southern and eastern rural Arkansas as compared to the rest of the state. This study provides evidence that the implementation of air pollution regulations has measurable effects on mortality even in regions with high prevalence of major risk factors such as obesity and smoking. These outcomes are noteworthy as efforts to modify the major risk factors require longer realization times

Molecular Speciation of Size Fractionated Particulate Water-Soluble Organic Carbon by Two-Dimensional Nuclear Magnetic Resonance (NMR) Spectroscopy

Particulate matter is associated with increased morbidity and mortality; its effects depend on particle size and chemical content. It is important to understand the composition and resultant toxicological profile of particulate organic compounds, the largest and most complex fraction of particulate matter. The objective of the study was to delineate the nuclear magnetic resonance (NMR) spectral fingerprint of the biologically relevant water-soluble organic carbon (WSOC) fraction of size fractionated urban aerosol. A combination of one and two-dimensional NMR spectroscopy methods was used. The size distribution of particle mass, water-soluble extract, non-exchangeable organic hydrogen functional types and specific biomarkers such as levoglucosan, methane sulfonate, ammonium and saccharides indicated the contribution of fresh and aged wood burning emissions, anthropogenic and biogenic secondary aerosol for fine particles as well as primary traffic exhausts and pollen for large particles. Humic-like macromolecules in the fine particle size range included branched carbon structures containing aromatic, olefinic, keto and nitrile groups and terminal carboxylic and hydroxyl groups such as terpenoid-like polycarboxylic acids and polyols. Our study show that 2D-NMR spectroscopy can be applied to study the chemical composition of size fractionated aerosols

Cytochrome P450-7B1 and 11β-hydroxysteroid dehydrogenase type 1 distribution in human tissues

AbstractSuccessive action of cytochrome P450-7B1 (CYP7B1) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on 3β-hydroxysteroids such as DHEA and epiandrosterone leads to the production of cytoprotective 7β-hydroxylated derivatives. Investigation of the presence of these enzymes in human tissues could be carried out on commercially available human tissue arrays with use of antibodies specific to CYP7B1 and 11β-HSD1 for immunohistochemistry. Both enzymes were detected mainly in tissues of endodermic and ectodermic origin which are prone to undergo inflammation. As low doses of the 7β-hydroxylated derivatives of DHEA and epiandrosterone trigger the resolution of inflammation and tissue repair, CYP7B1 and 11β-HSD1 tissue contents may reflect the tissue ability for reparation after pathological conditions.</jats:p