Corticosteroid suppression of lipoxin A4 and leukotriene B4from alveolar macrophages in severe asthma

<p>Abstract</p> <p>Background</p> <p>An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B₄(LTB₄), and lipoxin A₄(LXA₄) production by alveolar macrophages (AMs) and studied the impact of corticosteroids.</p> <p>Methods</p> <p>AMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 μg/ml) with or without dexamethasone (10^-6M). LTB₄and LXA₄were measured by enzyme immunoassay.</p> <p>Results</p> <p>LXA₄biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA₄induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB₄were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB₄was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB₄and LXA₄, with lesser suppression of LTB₄in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA₄and FEV₁(% predicted) (r_s= 0.60; p < 0.01).</p> <p>Conclusions</p> <p>Decreased LXA₄and increased LTB₄generation plus impaired corticosteroid sensitivity of LPS-induced LTB₄but not of LXA₄support a role for AMs in establishing a pro-inflammatory balance in severe asthma.</p

Fermi Large Area Telescope observations of PSR J1836+5925

The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8 million years, a spindown luminosity of 1.1$\times10^{34}$ erg s$^{-1}$, and a large off-peak emission component, making it quite unusual among the known gamma-ray pulsar population. We present an analysis of one year of LAT data, including an updated timing solution, detailed spectral results and a long-term light curve showing no indication of variability. No evidence for a surrounding pulsar wind nebula is seen and the spectral characteristics of the off-peak emission indicate it is likely magnetospheric. Analysis of recent XMM observations of the X-ray counterpart yields a detailed characterization of its spectrum, which, like Geminga, is consistent with that of a neutron star showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa

TEST-RETEST RELIABILITY OF TETRAX® STATIC POSTUROGRAPHY SYSTEM IN YOUNG ADULTS WITH LOW PHYSICAL ACTIVITY LEVEL.

PURPOSE/BACKGROUND: Assessment of postural sway with force plates can be affected by type of measurement and various clinical parameters such as age and activity level of the individual person. For this reason, variability is detected in postural reactions of healthy subjects without balance impairment. Test-retest reliability of postural sway in adolescent athletes has been measured using a force plate and additional test-retest studies have been suggested for subjects of different age groups with different activity levels. Therefore, the purpose of this research was to assess test-retest reliability of Tetrax® Static Posturography in young adults with low physical activity level, and examine the relationship between posturography results and low activity level. METHODS: Young adults older than 18 years of age were included in the study. Demographic characteristics of the cases were recorded including age, weight, height, body mass index (BMI, kg/m2) and dominant extremity. Number of falls in the previous six months, lower body endurance (sit to stand test) and single-leg eyes closed stance test were recorded. Activity level of participants was determined according to the International Physical Activity Questionnaire (IPAQ). Posturographic evaluation of all volunteers was completed using the Tetrax® Interactive Postural Balance System (Sunlight Medical Ltd, Israel). Fall risk and general stability index (SI) calculated by the Tetrax® were recorded. Following the first test, measurements were repeated 24 to 48 hours later for reliability purposes. RESULTS: Sixty-five subjects (28 male, 37 female; mean age 22.2 ± 1.1 years, mean BMI 22.6 ± 3.3 kg/m(2)) were evaluated. All participants were classified as minimally active according to mean IPAQ score (1042.1 ± 517.7 [231 - 2826] MET- minutes per week). ICC scores between the first and second tests for fall index and total stability index were excellent (ICC2,1=0.858, 0.850, respectively). Fall risk determined by using the Tetrax® device was negatively correlated with lower body endurance (p=0.001, r=-0.446), vigorous activity score (p=0.011, -0.312) and total activity score (p=0.029, r=-0.271), and positively correlated with single leg stance score (p=0.001, r=0.606). There was a weak correlation between fall risk history and the fall risk determined by using Tetrax® device (p=0.04, r=0.255). There were no correlations between fall risk and height, weight, and BMI (p>0.05). CONCLUSIONS: The results demonstrated the high test-retest reliability of Tetrax® interactive balance system in young healthy adults with low physical activity level. Future studies are needed to determine the effectiveness of increasing physical activity level on postural control. LEVEL OF EVIDENCE: III