Susan A. Jansen

Cyclooxygenase-2-specific Inhibitor Improves Functional Outcomes, Provides Neuroprotection, and Reduces Inflammation in a Rat Model of Traumatic Brain Injury

OBJECTIVE:Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. METHODS:DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model. RESULTS:DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3–immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3–immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuroprotective endocannabinoid, in the injured brain. CONCLUSION:These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials.

Vanadia Catalysts on Anatase, Rutile, and TiO2(B) for the Ammoxidation of Toluene: An ESR and High-Resolution Electron Microscopy Characterization

Three titania polymorphs, anatase, rutile, and TiO2(B), were used as supports for vanadia. Catalysts with nominal loadings corresponding to 1.5 and 5 theoretical layers were prepared. True monolayer samples were obtained by NH3(aq)-treatment of the samples with 5 nominal vanadia layers. Prepared catalysts were characterized by chemical analysis, ESR, and high-resolution electron microscopy. It was observed that an almost complete monolayer of vanadia can be formed on anatase and TiO2(B). The monolayer on TiO2(B) consists of V4+ species. A magnetic species attributable to tetrahedral states of vanadium was found to dominate the ESR resonance. Chemical analysis of the monolayer on anatase showed the presence of both V4+ and V4+ species. The ESR spectrum indicated a high degree of V4+-V4+ interaction. From the characterizations of rutile-supported samples it seems that the support interface is a solid solution of V4+. On all supports, vanadium on top of the monolayer is present as V5+. High-resolution micrographs of the samples with the highest loading revealed the formation of amorphous vanadia on both anatase and rutile. On TiO2(B), vanadia was found to grow coherently at the titania interface. The catalysts were used in the oxidation and ammoxidation of toluene to benzaldehyde and benzonitrile, respectively. Considering both activity and selectivity, multilayers of vanadia supported on TiO2(B) show a good performance for both reactions.

Development and validation of a high-performance liquid chromatography–electrospray mass spectrometry method for the simultaneous determination of 23 eicosanoids

Inflammation is implicated in the pathogenesis of a number of diseases, including cardiovascular disease. Current research is focused on developing assays to search for biomarkers for inflammation. Eicosanoids are the oxidative metabolites of arachidonic acid (eicosatetraenoic acid, AA), a long chain polyunsaturated fatty acid common in Western diets. AA can be oxidized by one of three pathways to form prostaglandins (PGs), leukotrienes (LTs), or a number of hydroxyl and epoxy compounds. These eicosanoids have a variety of physiological functions, including regulating inflammation. We have developed a method utilizing LC-MS to separate and quantitate 23 different eicosanoids from all the three oxidative pathways. The eicosanoids were separated using a gradient elution of acetonitrile with 0.1% formic acid (v/v) and water with 0.1% formic acid (v/v) at a flow rate of 1 mL/min with a Symmetry C18 column (250 mm x 4.6 mm). Deuterated eicosanoids were used as internal standards for quantitation. Mass spectrometric detection was carried out using an Agilent 1100-series LC-MSD with an electrospray ionization interface. Electrospray ionisation (ESI) mass spectra were acquired using negative ionization and selective ion monitoring. The method was validated and shown to be sensitive (LOQ at pg levels for most compounds), accurate (recovery values 75-120%) and precise (R.S.D.<20 for all compounds) with a linear range over several orders of magnitude. The method was applied to rat kidney tissue and shown to be indicative of the eicosanoid levels within a specific organ. The analysis of eicosanoids can provide insight into the inflammatory mechanisms associated with cardiovascular disease.

The reduction of dissolved iron species by humic acid and subsequent production of reactive oxygen species

Abstract Humic acid (HA) is distributed throughout the environment. Many of its properties are known, but its exact structure and function are still in question. To understand the chemistry and biochemical implications of HA on living systems we have focused on understanding radical chemistries of HA in the presence of molecular oxygen and hydrogen peroxide. The work presented here uses EPR spectroscopy to demonstrate that Fe(III) is reduced to Fe(II) by peat derived HA (PHA), and that Fe(III) is reduced by PHA more efficiently when bound to chelators. However, desferroxamine (DFOM) sequesters Fe(III) from being reduced by PHA and inhibits the Fenton reaction. The reduction of molecular oxygen by Fe(II) gives H 2 O 2 as a significant product. The hydroxyl radical is also produced in this reduction process and is trapped by 5-Diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO). In addition to the formation of H 2 O 2 and OH, another oxidant also appears to be present. Although not isolated, this species displays the characteristics of the ferryl ion.

Structural modeling in humic acids

Abstract Humic acids are important biological and environmental materials; however, to date there are no significant reports confirming the primary or secondary structure of the building blocks of humic substances. In this work, we report a complementary experimental and computational study that utilizes molecular mechanical applications and spectroscopic tools to evaluate both the primary and secondary structural features of humic acids. The identification of an amide and pronounced CD response suggests a significant secondary structure for humic acids.

Evolution of the electronic states of polyaniline : an ab initio analysis of the orbital states of PAni synthons

Abstract In this work, ab initio computations performed using the B3LYP hybrid density functional are applied to describe the full electronic character of polyaniline (PAni) in terms of its logical structural subunits and/or its synthons. A complete description of bonding, redox states, and spectroscopic terms is obtained from this analysis, suggesting that structural and electronic properties of PAni are attributable to its synthons; aniline, p -phenylene diamine, and N , N ′-bis(4′-aminophenyl)-1,4-quinonediimine. Though previous modeling attempts with semi-empirical or simple Hartree–Fock methods have provided useful qualitative data, the ab initio/DFT approach used here has been shown to be quantitatively accurate. The general approach to understanding properties of complex materials in terms of its smaller structural units and synthons will be generally useful for polymers and complex clusters.

A review of analytical methods for eicosanoids in brain tissue

Eicosanoids are potent lipid mediators of inflammation and are known to play an important role in numerous pathophysiological processes. Furthermore, inflammation has been proven to be a mediator of diseases such as hypertension, atherosclerosis, Alzheimers disease, cancer and rheumatoid arthritis. Hence, these lipid mediators have gained significant attention in recent years. This review focuses on chromatographic and mass spectrometric methods that have been used to analyze arachidonic acid and its metabolites in brain tissue. Recently published analytical methods such as LC-MS/MS and GC-MS/MS are discussed and compared in terms of limit of quantitation and sample preparation procedures, including solid phase extraction and derivatization. Analytical challenges are also highlighted.

The role of adsorption of aniline trimers on the corrosion inhibition process: a ZINDO/1 study

Abstract The semi-empirical ZINDO/1 method is used to calculate the electronic structure and thermodynamic properties of aniline trimers adsorbed onto cluster models of the Al(100) and Fe(100) surfaces. The effects of progressive oxidation and protonation of the trimers on corrosion inhibition are interpreted in terms of these calculations.

Trimeric anilines as both donors and acceptors: an experimental and computational study

A series of donor/acceptor complexes are formed using the TTF, TCNE, and TCNQ with substituted aniline trimers in dilute acetonitrile solutions to investigate the relative success of the trimers as either electron donors or acceptors. Likewise, the effect of protonation by hydrochloric acid on the aniline trimers is investigated. Experimental results are harmonized with the results of high level density functional calculations, which reveal that trimer anilines are fascinatingly useful reagents in their own right.

Isolation of humic acid from the brown algaeAscophyllum nodosum, Fucus vesiculosus, Laminaria saccharina and the marine angiospermZostera marina

Recent discovery of humic acid (HA) in the free-living, brown algaPilayella littoralis has prompted a search for HA in other live plants. Marine algaeCodium fragile andMonostoma oxyspermum (greens),Chondrus crispus,Palmaria palmata andPolysiphonia lanosa (reds),Ascophyllum nodosum, Fucus vesiculosus andLaminaria saccharina (browns) andZostera marina (marine angiosperm) were investigated for their HA content. Only the brown algae and the marine angiosperm contained HA, which was extracted by a standard procedure augmented with necessary removal of alginic acid (where applicable). The isolated products were identified as HA by comparison of their analytical data, uv-visible, FTIR,1H NMR spectra and morphologies with those of authentic HA isolated from municipal compost.