Effect of Nonsteroid Anti-Inflammatory and Antipyretic Drugs on Prostaglandin Biosynthesis by Human Skin

There is increasing evidence that prostaglandins are mediators of inflammation in skin and that prostaglandins are synthesised locally in response to the inflammatory stimulus. The effect of four nonsteroid anti-inflammatory or antipyretic drugs on prostaglandin biosynthesis by human skin has therefore been studied. Aspirin (0.56 mM) and indomethacin (0.28 mM) produced a small but significant inhibition of synthesis of prostaglandin E2. Indomethacin and chloroquine, but not aspirin, inhibited synthesis of prostaglandin F2a. Acetaminophen inhibited synthesis of prostaglandin F2, but did not inhibit prostaglandin E2 synthesis. None of the drugs studied are therapeutically effective anti-inflammatory agents in human skin and it may be significant that the inhibitory effects of aspirin and indomethacin on prostaglandin synthesis by skin are small compared with the effects of the same drugs on prostaglandin synthesis in other tissues

Impacts of Co-Solvent Flushing on Microbial Populations Capable of Degrading Trichloroethylene

With increased application of co-solvent flushing technologies for removal of nonaqueous phase liquids from groundwater aquifers, concern over the effects of the solvent on native microorganisms and their ability to degrade residual contaminant has also arisen. This study assessed the impact of ethanol flushing on the numbers and activity potentials of trichloroethylene (TCE)-degrading microbial populations present in aquifer soils taken immediately after and 2 years after ethanol flushing of a former dry cleaners site. Polymerase chain reaction analysis revealed soluble methane monooxygenase genes in methanotrophic enrichments, and 16S rRNA analysis identified Methylocystis parvus with 98% similarity, further indicating the presence of a type II methanotroph. Dissimilatory sulfite reductase genes in sulfate-reducing enrichments prepared were also observed. Ethanol flushing was simulated in columns packed with uncontaminated soils from the dry cleaners site that were dosed with TCE at concentrations observed in the field; after flushing, the columns were subjected to a continuous flow of 500 pore volumes of groundwater per week. Total acridine orange direct cell counts of the flushed and nonflushed soils decreased over the 15-week testing period, but after 5 weeks, the flushed soils maintained higher cell counts than the nonflushed soils. Inhibition of methanogenesis by sulfate reduction was observed in all column soils, as was increasing removal of total methane by soils incubated under methanotrophic conditions. These results showed that impacts of ethanol were not as severe as anticipated and imply that ethanol may mitigate the toxicity of TCE to the microorganisms

The Iowa Homemaker vol.39, no.3

Dean LeBaron, Diane Rasmussen, page 5 Your Faculty’s Favorite Home-Work, Jill Gaylord, page 6 Why the Slouch?, Jane Gibson, page 8 My Trip Around the World, Jane Gibson, page 9 Off-Campus Commentary, Elizabeth McDonald, page 10 How Do You Rate As A Roomie?, Gail Devens, page 11 What’s Going On, page 1

An AI Approach to Identifying Novel Therapeutics for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that has a significant impact on quality of life and work capacity. Treatment of RA aims to control inflammation and alleviate pain; however, achieving remission with minimal toxicity is frequently not possible with the current suite of drugs. This review aims to summarise current treatment practices and highlight the urgent need for alternative pharmacogenomic approaches for novel drug discovery. These approaches can elucidate new relationships between drugs, genes, and diseases to identify additional effective and safe therapeutic options. This review discusses how computational approaches such as connectivity mapping offer the ability to repurpose FDA-approved drugs beyond their original treatment indication. This review also explores the concept of drug sensitisation to predict co-prescribed drugs with synergistic effects that produce enhanced anti-disease efficacy by involving multiple disease pathways. Challenges of this computational approach are discussed, including the availability of suitable high-quality datasets for comprehensive analysis and other data curation issues. The potential benefits include accelerated identification of novel drug combinations and the ability to trial and implement established treatments in a new index disease. This review underlines the huge opportunity to incorporate disease-related data and drug-related data to develop methods and algorithms that have strong potential to determine novel and effective treatment regimens

Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD.

INTRODUCTION: Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments. Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results. Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management. This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils. It also examined the repeatability of blood eosinophil counts. METHODS: Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts. Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia. Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts. RESULTS: Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×10(9)/L vs 0.15×10(9)/L; P<0.0001). Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001). Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001). At a threshold of ≥0.3×10(9)/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases. A threshold of ≥0.4×10(9)/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7). In contrast, ≥0.2×10(9)/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia. There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001). CONCLUSION: Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy

Influence of age, past smoking, and disease severity on tlr2, neutrophilic inflammation, and MMP-9 Levels in COPD

Chronic obstructive pulmonary disease (COPD) is a common and serious respiratory disease, particularly in older individuals, characterised by fixed airway obstruction and persistent airway neutrophilia. The mechanisms that lead to these features are not well established. We investigated the contribution of age, prior smoking, and fixed airflow obstruction on sputum neutrophils, TLR2 expression, and markers of neutrophilic inflammation. Induced sputum from adults with COPD (n = 69) and healthy controls (n = 51) was examined. A sputum portion was dispersed, total, differential cell count and viability recorded, and supernatant assayed for CXCL8, matrix metalloproteinase- (MMP-) 9, neutrophil elastase, and soluble TLR2. Peripheral blood cells (n = 7) were stimulated and TLR2 activation examined. TLR2 levels were increased with ageing, while sputum neutrophils and total sputum MMP-9 levels increased with age, previous smoking, and COPD. In multivariate regression, TLR2 gene expression and MMP-9 levels were significant independent contributors to the proportion of sputum neutrophils after adjustment for age, prior smoking, and the presence of airflow obstruction. TLR2 stimulation led to enhanced release of MMP-9 from peripheral blood granulocytes. TLR2 stimulation activates neutrophils for MMP-9 release. Efforts to understand the mechanisms of TLR2 signalling and subsequent MMP-9 production in COPD may assist in understanding neutrophilic inflammation in COPD. © 2013 Jodie L. Simpson et al

A Search for Oxygen in the Low-Density Lyman-alpha Forest Using the Sloan Digital Sky Survey

We use 2167 Sloan Digital Sky Survey (SDSS) quasar spectra to search for low-density oxygen in the Intergalactic Medium (IGM). Oxygen absorption is detected on a pixel-by-pixel basis by its correlation with Lyman-alpha forest absorption. We have developed a novel Locally Calibrated Pixel (LCP) search method that uses adjacent regions of the spectrum to calibrate interlopers and spectral artifacts, which would otherwise limit the measurement of OVI absorption. Despite the challenges presented by searching for weak OVI within the Lyman-alpha forest in spectra of moderate resolution and signal-to-noise, we find a highly significant detection of absorption by oxygen at 2.7 < z < 3.2 (the null hypothesis has a chi^2=80 for 9 data points). We interpret our results using synthetic spectra generated from a lognormal density field assuming a mixed quasar-galaxy photoionizing background (Haardt & Madau 2001) and that it dominates the ionization fraction of detected OVI. The LCP search data can be fit by a constant metallicity model with [O/H] = -2.15_(-0.09)^(+0.07), but also by models in which low-density regions are unenriched and higher density regions have a higher metallicity. The density-dependent enrichment model by Aguirre et al. (2008) is also an acceptable fit. All our successful models have similar mass-weighted oxygen abundance, corresponding to [_MW] = -2.45+-0.06. This result can be used to find the cosmic oxygen density in the Lyman-alpha forest, Omega_(Oxy, IGM) = 1.4(+-0.2)x10^(-6) = 3x10^(-4) Omega_b. This is the tightest constraint on the mass-weighted mean oxygen abundance and the cosmic oxygen density in the Lyman-alpha forest to date and indicates that it contains approximately 16% of metals produced by star formation (Bouch\'e et al. 2008) up to z = 3.Comment: 12 pages, 9 figures. Accepted by ApJ (minor changes

Environmental Regulation Can Arise Under Minimal Assumptions

Models that demonstrate environmental regulation as a consequence of organism and environment coupling all require a number of core assumptions. Many previous models, such as Daisyworld, require that certain environment-altering traits have a selective advantage when those traits also contribute towards global regulation. We present a model that results in the regulation of a global environmental resource through niche construction without employing this and other common assumptions. There is no predetermined environmental optimum towards which regulation should proceed assumed or coded into the model. Nevertheless, polymorphic stable states that resist perturbation emerge from the simulated co-evolution of organisms and environment. In any single simulation a series of different stable states are realised, punctuated by rapid transitions. Regulation is achieved through two main subpopulations that are adapted to slightly different resource values, which force the environmental resource in opposing directions. This maintains the resource within a comparatively narrow band over a wide range of external perturbations. Population driven oscillations in the resource appear to be instrumental in protecting the regulation against mutations that would otherwise destroy it. Sensitivity analysis shows that the regulation is robust to mutation and to a wide range of parameter settings. Given the minimal assumptions employed, the results could reveal a mechanism capable of environmental regulation through the by-products of organisms