Hepcidin-25 in chronic hemodialysis patients is related to residual kidney function and not to treatment with erythropoiesis stimulating agents

Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory- and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7 ± 13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory- and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p<0.001), hsCRP (p<0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p<0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance.     

Role of multi-drug resistance-associated protein-1 transporter in statin-induced myopathy

This study investigated the effects of probenecid to inhibit the multi-drug resistance-associated protein-1 (MRP-1) in mediating the efflux and myotoxicity in rat skeletal muscles, with administration of rosuvastatin. Male Sprague-Dawley rats were administered daily, for 15 days, with either rosuvastatin (50, 100 or 200 mg/kg) or probenecid (100 mg/kg) alone, or with a combination of rosuvastatin (50, 100 or 200 mg/kg) and probenecid (100 mg/kg). Skeletal muscle toxicity was elevated with probenecid administered with 200 mg/kg/day of rosuvastatin, with the elevation of creatine kinase by 12-fold, alanine aminotrasferase by 10-fold and creatinine by 9-fold at day 15, with no adverse effects observed when probenecid was given alone. Mitochondria ultrastructural damage with enlargement, disruption, cristolysis and vaculation was seen in the soleus and plantaris of animals administered with probenecid and high dosages of statin. These muscles were also expressing more succinic dehydrogenase (SDH)-positive and cytochrome oxidase (CyOX)-positive fibers. Although generally well-tolerated, statins produce a variety of adverse skeletal muscle events. Hydrophilic statins, with reduced levels of non-specific passive diffusion rates into extra-hepatic tissues, are still seen to produce myopathy. This highlights the important roles of transport mechanisms in statin transport at the skeletal muscles. Excessive influx, reduced efflux or the combination of the two could result in elevated cellular levels of statins at the skeletal muscles, resulting in toxicity. This study provides preliminary evidence that the MRP-1 transporter and efflux at skeletal muscles possibly play significant roles in statin-induced myopathy.     

Functional properties of the carboxy-terminal host cell-binding domains of the two toxins, TcdA and TcdB, expressed by Clostridium difficile

The biological and ligand-binding properties of recombinant C-terminal cell-binding domains (CBDs) and subdomains of the two large exotoxins, Toxin A (TcdA) and Toxin B (TcdB) expressed by Clostridium difficile were examined in the hemagglutination and Verocytotoxicity neutralization assays and by qualitative affinity chromatography using Sepharose-linked alpha Gal(1,3)betaGal(1,4)beta Glc as well as the direct electrospray ionization mass spectrometry (ES-MS) assay. These studies revealed that, whereas the full-length TcdA CBD agglutinated rabbit erythrocytes, neutralized TcdA-mediated Vero cell death and bound to alpha Gal(1,3)betaGal(1,4)beta Glc-derivatized Sepharose, the TcdB CBD was inactive in these functional assays. Moreover, retention by alpha Gal(1,3)betaGal(1,4)beta Glc-derivatized Sepharose corresponded to the number of available TcdA subdomain ligand-binding sites. By contrast, the ES-MS assays revealed that both the TcdA and TcdB CBD bind to 8-methoxycarbonyloctyl-alpha Gal(1,3)betaGal(1,4)beta Glc sequences with similar avidities. Additional ES-MS experiments using chemically altered alpha Gal(1,3)betaGal(1,4)beta Glc sequences also revealed that the TcdA and TcdB CBD will tolerate a fair amount of structural variation in their complementary glycan ligands. Although the studies are consistent with the known ligand-binding properties of the TcdA and TcdB holotoxins, they also revealed subtle heretofore unrecognized functional differences in their receptor recognition properties.     

40 Phytoplankton biomass and community dynamics in the lake pont-chartrain estuary of southeast louisiana, usa: effects of light and nutrients upon seasonal and spatial patterns

A yearlong study (2002–2003) was conducted in the Lake Pontchartrain Estuary (LPE) of Southeast Louisiana in order to examine the temporal and spatial variability of phytoplankton biomass and community dynamics in relation to nutrients, light climate and other abiotic parameters. Variability was assessed through a north-south transect across the estuary and at five of the major tributaries of the LPE at bi-weekly intervals. Phytoplankton pigmentation was analyzed by HPLC and used to calculate biomass (as chlorophyll a) and to determine the relative abundances of phylogenetic groups and taxa (via CHEMTAX). Microscopic analyses of select samples were used to verify the efficacy of the CHEMTAX method in the waters of the LPE. Water-column up-/down-welling irradiance (PAR) and colored dissolved organic matter (CDOM) measurements were used to characterize the light climate. Results indicate that LPE phytoplankton biomass and community composition are: 1) highly variable at the spatial and temporal scales of this study, 2) can significantly impact the light field of the LPE, and 3) are influenced by macro-nutrient ratios.     

Modulatory Effects of the Piccolo Genotype on Emotional Memory in Health and Depression

Major depressive disorder (MDD) has been associated with biased memory formation for mood-congruent information, which may be related to altered monoamine levels. The piccolo (PCLO) gene, involved in monoaminergic neurotransmission, has previously been linked to depression in a genome-wide association study. Here, we investigated the role of the PCLO risk allele on functional magnetic resonance imaging (MRI) correlates of emotional memory in a sample of 89 MDD patients (64 PCLO risk allele carriers) and 29 healthy controls (18 PCLO risk allele carriers). During negative word encoding, risk allele carriers showed significant lower activity relative to non-risk allele carriers in the insula, and trend-wise in the anterior cingulate cortex and inferior frontal gyrus. Moreover, depressed risk allele carriers showed significant lower activity relative to non-risk allele carriers in the striatum, an effect which was absent in healthy controls. Finally, amygdalar response during processing new positive words vs. known words was blunted in healthy PCLO+ carriers and in MDD patients irrespective of genotype, which may indicate that signalling of salient novel information does not occur to the same extent in PCLO+ carriers and MDD patients. The PCLO risk allele may increase vulnerability for MDD by modulating local brain function with regard to responsiveness to salient stimuli (i.e. insula) and processing novel negative information. Also, depression-specific effects of PCLO on dorsal striatal activation during negative word encoding and the absence of amygdalar salience signalling for novel positive information further suggest a role of PCLO in symptom maintenance in MDD.     

A method of DNA isolation from epiphytic CAM ferns for use in random amplified polymorphic DNA analysis

A method for DNA extraction from Pyrrosia piloselloides (L.) Price and Pyrrosia longifolia (Burm.) Morton utilising hexadecyltrimethylammonium bromide is described. The genomic DNA isolated was found to be relatively pure and shown to be suitable for RAPD analysis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Harmonizing Energy and Power Density toward 2.7 V Asymmetric Aqueous Supercapacitor

Tremendous research efforts are devoted to developing wide potential window aqueous supercapacitors to resolve their low energy density concern. While the operational potential window is dictated by the intrinsic electrochemical stability of water (1.23 V), such a bottleneck may be surpassed by leveraging the additional overpotential of the oxygen evolution reaction and the hydrogen evolution reaction (HER). Herein, by employing an electroreduction technique, Na⁺ is adsorbed onto the carbon negative electrode which effectively acts as a physical barrier to hinder intermediate HER product formation, thereby reducing HER activity. To complement the wide potential carbon electrode, Na_0.25MnO₂ is employed as the positive electrode to take advantage of the extra energy (i.e., increased overpotential) required for Na⁺ insertion process into the structure. The asymmetric supercapacitor exhibits high energy density of 61.1 W h kg^?1 at a power density of 982 W kg^?1, and even at an ultrahigh power density of 42.9 kW kg^?1, a respectable energy density of 16.3 W h kg^?1 is attained. In addition, 93.7% capacitance retention is recorded after cycling for 10 000 cycles which further demonstrates its suitability as supercapacitor. The present success in fabricating a 2.7 V asymmetric supercapacitor will open a promising research route toward achieving high energy density and high power density.     

<Emphasis Type="Italic">Brevibacterium anseongense</Emphasis> sp. nov., isolated from soil of ginseng field

Gram-positive, aerobic, non-motile, pale-yellow, and rodshaped bacterium, designated as Gsoil 188^T, was isolated from the soil of a ginseng field in Pocheon, South Korea. A phylogenetic analysis based on 16S rRNA gene sequence comparison revealed that the strain formed a distinct lineage within the genus Brevibacterium and was most closely related to B. epidermidis NBRC 14811^T (98.4%), B. sediminis FXJ8.269^T (98.2%), B. avium NCFB 3055^T (98.1%), and B. oceani BBH7^T (98.1%), while it shared less than 98.1% identity with the other species of this genus. The DNA G + C content was 68.1 mol%. The predominant quinone was MK-8(H₂). The major fatty acids were anteiso-C_15:0 and anteiso-C_17:0. The cell wall peptidoglycan of strain Gsoil 188^T contained meso-diaminopimelic acid. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, and an unidentified aminolipid. The physiological and biochemical characteristics, low DNA-DNA relatedness values, and taxonomic analysis allowed the differentiation of strain Gsoil 188^T from the other recognized species of the genus Brevibacterium. Therefore, strain Gsoil 188^T represents a novel species of the genus Brevibacterium, for which the name Brevibacterium anseongense sp. nov. is proposed, with the type strain Gsoil 188^T (= KACC 19439^T = LMG 30331^T).