Changes of coronary plaque composition correlate with C-reactive protein levels in patients with ST-elevation myocardial infarction following high-intensity statin therapy.

OBJECTIVES Levels of inflammatory biomarkers associate with changes of coronary atheroma burden in statin-treated patients with stable coronary artery disease. This study sought to determine changes of plaque composition in vivo in relation to high-sensitivity C-reactive protein (hs-CRP) levels in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin therapy. METHODS The IBIS-4 study performed serial (baseline and 13-month), 2-vessel intravascular ultrasound (IVUS) and radiofrequency-IVUS of the non-infarct-related arteries in patients with STEMI treated with high-intensity statin therapy. The present analysis included 44 patients (80 arteries) with serial measurements of hs-CRP. RESULTS At follow-up, median low-density lipoprotein cholesterol (LDL-C) levels decreased from 126 to 77 mg/dl, HDL-C increased from 44 to 47 mg/dl, and hs-CRP decreased from 1.6 to 0.7 mg/L. Regression of percent atheroma volume (-0.99%, 95% CI -1.84 to -0.14, p = 0.024) was accompanied by reduction of percent fibro-fatty (p = 0.04) and fibrous tissue (p < 0.001), and increase in percent necrotic core (p = 0.006) and dense calcium (p < 0.001). Follow-up levels of hs-CRP, but not LDL-C, correlated with changes in percent necrotic core (p = 0.001) and inversely with percent fibrous tissue volume (p = 0.008). Similarly, baseline-to-follow-up change of hs-CRP correlated with the change in percent necrotic core volume (p = 0.02). CONCLUSIONS In STEMI patients receiving high-intensity statin therapy, stabilization of VH-IVUS-defined necrotic core was confined to patients with lowest on-treatment levels and greatest reduction of hs-CRP. Elevated CRP levels at follow-up may identify progression of high-risk coronary plaque composition despite intensive statin therapy and overall regression of atheroma volume.

Mechanism of N-(4-hydroxyphenyl)retinamide (4HPR)-induced apoptosis in head and neck squamous cell carcinoma cells

4HPR is a synthetic retinoid that has shown chemopreventive and therapeutic efficacy against premalignant and malignant lesions including oral leukoplakia, ovarian and breast cancer and neuroblastoma in clinical trials. 4HPR induces growth inhibition and apoptosis in various cancer cells including head and neck squamous cell carcinoma (HNSCC) cells. 4HPR induces apoptosis by several mechanisms including increasing reactive oxygen species (ROS), or inducing mitochondrial permeability transition (MPT). 4HPR has also been shown to modulate the level of different proteins by transcriptional activation or posttranslational modification in various cellular contexts. However, the mechanism of its action is not fully elucidated. In this study, we explored the mechanism of 4HPR-induced apoptosis in HNSCC cells. ^ First, we identified proteins modulated by 4HPR by using proteomics approaches including: Powerblot western array and 2-dimensional polyacrylamide gel electrophoresis. We found that 4HPR modulated the levels of several proteins including c-Jun. Further analysis has shown that 4HPR induced activation of Activator Protein 1 (AP-1) components, c-Jun and ATF-2. We also found that 4HPR increased the level of Heat shock protein (Hsp) 70 and phosphorylation of Hsp27. ^ Second, we found that 4HPR induced prolonged activation of JNK, p38/MAPK and extracellular signal-regulated kinase (ERK). We also demonstrated that the activation of these kinases is required for 4HPR-induced apoptosis. JNK inhibitor SP600125 and siRNA against JNK1 and JNK2 suppressed, while overexpression of JNK1 enhanced 4HPR-induced apoptosis. p38/MAPK inhibitor PD169316 and MEK1/2 inhibitor PD98059 also suppressed 4HPR-induced apoptosis. We also demonstrated that activation of JNK, p38/MAPK and ERK is triggered by ROS generation induced by 4HPR. We also found that translation inhibitor, cycloheximide, suppressed 4HPR-induced apoptosis through inhibition of 4HPR-induced events (e.g. ROS generation, cytochrome c release, JNK activation and suppression of Akt). We also demonstrated that MPT is involved in 4HPR-induced apoptosis. ^ Third, we demonstrated the presence of NADPH oxidase in HNSCC 2B cells. We also found that 4HPR increased the level of the p67phox, a subunit of NADPH oxidase which participates in ROS production and apoptosis induced by 4HPR. ^ The novel insight into the mechanism by which 4HPR induces apoptosis can be used to improve design of future clinical studies with this synthetic retinoid in combination with specific MAPK modulators. ^

Tab. 1: Results of the movement measurements on the blue ice-field Blåisen

In January/February 1985 a German-South African expedition had the opportunity to repeat measurements made by means of stakes planted in 1951 (Norwegian-British-Swedish Antarctic Expedition 1949-52) and 1966 (SANAE VII). Although the rediscovery of the old stakes had not been expected, the stakes could be identified and it was possible to derive movement vectors on the basis of old and heterogenic measurement data. The long-term movement rates established basically confirm and complement the values determined in 1951. The flow rates of 9,1 cm/a to 66.4 cm/a proved to be extremly low. Observations of the stake lengths showed very little accumulation in the fringe areas of the blue ice-field (ca. 0.7 to 2.6 cm/a snow/firn); on bare ice an ablation of 2.6 cm/a water equivalent (2.9 cm/a ice) was measured. The paper begins with a description of the essential conditions for the formation of the blue ice-field. Subsequently the measurements are explained in detail and their results are discussed.

Spatially explicit estimates of length and biomass of Micromesistius poutassou (Blue Whiting) and Clupea harengus (Norwegian spring spawning herring) from acoustic and trawl surveys in the North-East Atlantic (2004-2012)

Acoustic estimates of herring and blue whiting abundance were obtained during the surveys using the Simrad ER60 scientific echosounder. The allocation of NASC-values to herring, blue whiting and other acoustic targets were based on the composition of the trawl catches and the appearance of echo recordings. To estimate the abundance, the allocated NASC -values were averaged for ICES-squares (0.5° latitude by 1° longitude). For each statistical square, the unit area density of fish (rA) in number per square nautical mile (N*nm-2) was calculated using standard equations (Foote et al., 1987; Toresen et al., 1998). To estimate the total abundance of fish, the unit area abundance for each statistical square was multiplied by the number of square nautical miles in each statistical square and then summed for all the statistical squares within defined subareas and over the total area. Biomass estimation was calculated by multiplying abundance in numbers by the average weight of the fish in each statistical square then summing all squares within defined subareas and over the total area. The Norwegian BEAM soft-ware (Totland and Godø 2001) was used to make estimates of total biomass.

Spatially explicit estimates of length and biomass of Micromesistius poutassou (Blue Whiting) from acoustic and trawl surveys in the North-East Atlantic in May 2005

Acoustic estimates of herring and blue whiting abundance were obtained during the surveys using the Simrad ER60 scientific echosounder. The allocation of NASC-values to herring, blue whiting and other acoustic targets were based on the composition of the trawl catches and the appearance of echo recordings. To estimate the abundance, the allocated NASC -values were averaged for ICES-squares (0.5° latitude by 1° longitude). For each statistical square, the unit area density of fish (rA) in number per square nautical mile (N*nm-2) was calculated using standard equations (Foote et al., 1987; Toresen et al., 1998). To estimate the total abundance of fish, the unit area abundance for each statistical square was multiplied by the number of square nautical miles in each statistical square and then summed for all the statistical squares within defined subareas and over the total area. Biomass estimation was calculated by multiplying abundance in numbers by the average weight of the fish in each statistical square then summing all squares within defined subareas and over the total area. The Norwegian BEAM soft-ware (Totland and Godø 2001) was used to make estimates of total biomass.

Collection of data on particulate and dissolved soil phosphorus in the Jena Experiment (Main Experiment, time series since 2002)

This data set contains two time series of measurements of dissolved phosphorus (organic, inorganic and total with a biweekly resolution) and dissolved inorganic phosphorus with a seasonal resolution. In addition, data on phosphorus from soil samples measured in 2007 and fractionated by different acid-extrations (Hedley fractions) are provided. All data measured at the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. 1. Dissolved phosphorus in soil solution: Suction plates installed on the field site in 10, 20, 30 and 60 cm depth were used to sample soil pore water. Cumulatively extracted soil solution was collected every two weeks from October 2002 to May 2006. The biweekly samples from 2002, 2003 and 2004 were analyzed for dissolved organic phosphorus (DOP), dissolved inorganic phosphorus (PO4P) and dissolved total phosphorus (TDP) by Continuous Flow Analyzer (CFA SAN ++, SKALAR [Breda, The Netherlands]). 2. Seasonal values of dissolved inorganic phosphorus in soil solution were calculated as volume-weighted mean values of the biweekly measurements (spring = March to May, summer = June to August, fall = September to November, winter = December to February). 3. Phosphorus fractions in soil: Five independent soil samples per plot were taken in a depth of 0-15 cm using a soil corer with an inner diameter of 1 cm. The five samples per plot were combined to one composite sample per plot. A four-step sequential P fractionation (Hedley fractions) was applied and concentrations of P fractions in soil were measured photometrically (molybdenum blue-reactive P) with a Continuous Flow Analyzer (Bran&Luebbe, Germany).

Phosphorus fractions in soil of the Jena Experiment (Main Experiment, year 2007)

This data set contains measurements of phosphorus fractions (Hedley fractions) in soil collected 2007 from the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. Soil sampling and analysis: Five independent soil samples per plot were taken in a depth of 0-15 cm using a soil corer with an inner diameter of 1 cm. The five samples per plot were combined to one composite sample per plot. A four-step sequential P fractionation (Hedley fractions) was applied. Sequentially, 20 ml NaHCO3 (adjusted to pH 8.5), 30 ml NaOH, and 35 ml HCl were used as extraction solutions for 0.5 g soil. The last step comprised the combustion (550 °C) of the remaining soil to destroy all organic material followed by shaking with 20 ml H2SO4. Organic P concentrations of the respective fractions were calculated as the difference between total dissolved P and inorganic P. Duplicate phosphate concentrations of P fractions in soil were measured photometrically (molybdenum blue-reactive P) with a Continuous Flow Analyzer (Bran&Luebbe, Germany).

Spatially explicit estimates of length and biomass of Micromesistius poutassou (Blue Whiting) from acoustic and trawl surveys in the North-East Atlantic in May 2009

Acoustic estimates of herring and blue whiting abundance were obtained during the surveys using the Simrad ER60 scientific echosounder. The allocation of NASC-values to herring, blue whiting and other acoustic targets were based on the composition of the trawl catches and the appearance of echo recordings. To estimate the abundance, the allocated NASC -values were averaged for ICES-squares (0.5° latitude by 1° longitude). For each statistical square, the unit area density of fish (rA) in number per square nautical mile (N*nm-2) was calculated using standard equations (Foote et al., 1987; Toresen et al., 1998). To estimate the total abundance of fish, the unit area abundance for each statistical square was multiplied by the number of square nautical miles in each statistical square and then summed for all the statistical squares within defined subareas and over the total area. Biomass estimation was calculated by multiplying abundance in numbers by the average weight of the fish in each statistical square then summing all squares within defined subareas and over the total area. The Norwegian BEAM soft-ware (Totland and Godø 2001) was used to make estimates of total biomass.

Phosphate d18O pore-water profiles of sediment core GeoB11807-2 and GeoB11804-4

Phosphorus cycling in the ocean is influenced by biological and geochemical processes that are reflected in the oxygen isotope signature of dissolved inorganic phosphate (Pi). Extending the Pi oxygen isotope record from the water column into the seabed is difficult due to low Pi concentrations and small amounts of marine porewaters available for analysis. We obtained porewater profiles of Pi oxygen isotopes using a refined protocol based on the original micro-extraction designed by Colman (2002). This refined and customized method allows the conversion of ultra-low quantities (0.5 - 1 µmol) of porewater Pi to silver phosphate (Ag3PO4) for routine analysis by mass spectrometry. A combination of magnesium hydroxide co-precipitation with ion exchange resin treatment steps is used to remove dissolved organic matter, anions, and cations from the sample before precipitating Ag3PO4. Samples as low as 200 µg were analyzed in a continuous flow isotope ratio mass spectrometer setup. Tests with external and laboratory internal standards validated the preservation of the original phosphate oxygen isotope signature (d18OP) during micro extraction. Porewater data on d18OP has been obtained from two sediment cores of the Moroccan margin. The d18OP values are in a range of +19.49 to +27.30 per mill. We apply a simple isotope mass balance model to disentangle processes contributing to benthic P cycling and find evidence for Pi regeneration outbalancing microbial demand in the upper sediment layers. This highlights the great potential of using d18OP to study microbial processes in the subseafloor and at the sediment water interface.