bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the Src kinase inhibitor saracatinib (AZD0530) on bone turnover in healthy men: A randomized, double-blind, placebo-controlled, multiple-ascending-dose phase I trial
Authors: Hannon Rosemary A , Clack Glen , Rimmer Martin , Swaisland Alan , Lockton J Andrew , Finkelman Richard D , Eastell Richard
Published: September 2009

Src is a nonreceptor tyrosine kinase thought to be essential for osteoclast function and bone resorption. We investigated the effect of the orally available Src inhibitor saracatinib (AZD0530) on bone turnover in healthy men. The study was part of a randomized, double-blind, placebo-controlled multiple-ascending-dose phase I trial of saracatinib. Fifty-nine healthy men (mean age 34.6 years) were divided into five cohorts; four with 12 subjects and one with 11 subjects, and randomized within each cohort in the ratio 3:1 to receive a single dose of saracatinib or placebo, respectively, followed 7 to 10 days later with daily doses for a further 10 to 14 days. Dosing levels of saracatinib ascended by cohort (60 to 250 mg). Markers of bone turnover were measured predose and 24 and 48 hours after the initial single dose and immediately before and 24 and 48 hours and 10 to 14 days after the final dose. Data from 44 subjects were included in the analysis. There was a dose-dependent decrease in bone resorption markers [serum cross-linked C-telopeptide of type I collagen (sCTX) and urinary cross-linked N-telopeptide of type I collagen normalized to creatinine (uNTX/Cr)]. At a dose of 250 mg (maximum tolerated dose), sCTX decreased by 88% [95% confidence interval (CI) 84–91%] and uNTX/Cr decreased by 67% (95% CI 53–77%) from baseline 24 hours after the final dose. There was no significant effect on bone formation markers. There were no significant adverse events. We conclude that inhibition of Src reduces osteoclastic bone resorption in humans. Saracatinib is a potentially useful treatment for diseases characterized by increased bone resorption, such as metastatic bone disease and osteoporosis. © 2010 American Society for Bone and Mineral Research
Phosphorylation-dependent inhibition of mineralization by osteopontin ASARM peptides is regulated by PHEX cleavage
Authors: Addison William N , Masica David L , Gray Jeffrey J , McKee Marc D
Published: September 2009

The SIBLING family (small integrin-binding ligand N-linked glycoproteins) of mineral-regulating proteins, which includes matrix extracellular phosphoglycoprotein (MEPE) and osteopontin (OPN), contains an acidic serine- and aspartate-rich motif (ASARM). X-linked hypophosphatemia caused by inactivating mutations of the PHEX gene results in elevated mineralization-inhibiting MEPE-derived ASARM peptides. Although the OPN ASARM motif shares 60% homology with MEPE ASARM, it is still unknown whether OPN ASARM similarly inhibits mineralization. In this study we have examined the role of OPN ASARM and its interaction with PHEX enzyme using an osteoblast cell culture model, mass spectrometry, mineral-binding assays, and computational modeling. MC3T3-E1 osteoblast cultures were treated with differently phosphorylated OPN ASARM peptides [with 5 phosphoserines (OpnAs5) or 3 phosphoserines (OpnAs3)] or with control nonphosphorylated peptide (OpnAs0). Phosphorylated peptides dose-dependently inhibited mineralization, and binding of phosphorylated peptides to mineral was confirmed by a hydroxyapatite-binding assay. OpnAs0 showed no binding to hydroxyapatite and did not inhibit culture mineralization. Computational modeling of peptide-mineral interactions indicated a favorable change in binding energy with increasing phosphorylation consistent with hydroxyapatite-binding experiments and inhibition of culture mineralization. Addition of PHEX rescued inhibition of mineralization by OpnAs3. Mass spectrometry of cleaved peptides after ASARM-PHEX incubations identified OpnAs3 as a PHEX substrate. We conclude that OPN ASARM inhibits mineralization by binding to hydroxyapatite in a phosphorylation-dependent manner and that this inhibitor can be cleaved by PHEX, thus providing a mechanistic explanation for how loss of PHEX activity in X-linked hyposphosphatemia can lead to extracellular matrix accumulation of ASARM resulting in the osteomalacia. © 2010 American Society for Bone and Mineral Research
Heterogeneity in Subcortical Brain Development: A Structural Magnetic Resonance Imaging Study of Brain Maturation from 8 to 30 Years
Authors: Østby Ylva , Tamnes Christian K. , Fjell Anders M. , Westlye Lars T. , Due-Tønnessen Paulina , Walhovd Kristine B.
Published: September 2009

Brain development during late childhood and adolescence is characterized by decreases in gray matter (GM) and increases in white matter (WM) and ventricular volume. The dynamic nature of development across different structures is, however, not well understood, and the present magnetic resonance imaging study took advantage of a whole-brain segmentation approach to describe the developmental trajectories of 16 neuroanatomical volumes in the same sample of children, adolescents, and young adults (n= 171; range, 8–30 years). The cerebral cortex, cerebral WM, caudate, putamen, pallidum, accumbens area, hippocampus, amygdala, thalamus, brainstem, cerebellar GM, cerebellar WM, lateral ventricles, inferior lateral ventricles, third ventricle, and fourth ventricle were studied. The cerebral cortex was further analyzed in terms of lobar thickness and surface area. The results revealed substantial heterogeneity in developmental trajectories. GM decreased nonlinearly in the cerebral cortex and linearly in the caudate, putamen, pallidum, accumbens, and cerebellar GM, whereas the amygdala and hippocampus showed slight, nonlinear increases in GM volume. WM increased nonlinearly in both the cerebrum and cerebellum, with an earlier maturation in cerebellar WM. In addition to similarities in developmental trajectories within subcortical regions, our results also point to differences between structures within the same regions: among the basal ganglia, the caudate showed a weaker relationship with age than the putamen and pallidum, and in the cerebellum, differences were found between GM and WM development. These results emphasize the importance of studying a wide range of structural variables in the same sample, for a broader understanding of brain developmental principles.
Regulation of Gonadotropin-Releasing Hormone Secretion by Kisspeptin/Dynorphin/Neurokinin B Neurons in the Arcuate Nucleus of the Mouse
Authors: Navarro Victor M. , Gottsch Michelle L. , Chavkin Charles , Okamura Hiroaki , Clifton Donald K. , Steiner Robert A.
Published: September 2009

Kisspeptin is encoded by theKiss1gene, and kisspeptin signaling plays a critical role in reproduction. In rodents, kisspeptin neurons in the arcuate nucleus (Arc) provide tonic drive to gonadotropin-releasing hormone (GnRH) neurons, which in turn supports basal luteinizing hormone (LH) secretion. Our objectives were to determine whetherpreprodynorphin(Dyn) andneurokinin B(NKB) are coexpressed inKiss1neurons in the mouse and to evaluate its physiological significance. Usingin situhybridization, we found thatKiss1neurons in the Arc of female mice not only express theDynandNKBgenes but also theNKB receptorgene (NK3) and theDyn receptor[the κ opioid receptor (KOR)] gene. We also found that expression of theDyn,NKB,KOR, andNK3in the Arc are inhibited by estradiol, as has been established forKiss1, and confirmed that Dyn and NKB inhibit LH secretion. Moreover, usingDynandKORknock-out mice, we found that long-term disruption ofDyn/KORsignaling compromises the rise of LH after ovariectomy. We propose a model whereby NKB and dynorphin act autosynaptically on kisspeptin neurons in the Arc to synchronize and shape the pulsatile secretion of kisspeptin and drive the release of GnRH from fibers in the median eminence.
A Chimera Analysis ofPrestinKnock-Out Mice
Authors: Cheatham Mary Ann , Low-Zeddies Sharon , Naik Khurram , Edge Roxanne , Zheng Jing , Anderson Charles T. , Dallos Peter
Published: September 2009

A chimera is a genetic composite containing a unique mix of cells derived from more than one zygote. This mouse model allows one to learn how cells of contrasting genotype functionally interactin vivo. Here, we investigate the effect that different proportions of prestin-containing outer hair cells (OHC) have on cochlear amplification. To address this issue, we developed a prestin chimeric mouse in which both ROSA26 wild-type (WT) andprestinknock-out (KO) genotypes are present in a single cochlea. The WT ROSA26 mice express a cell marker, allowing one to identify cells originating from the WT genome. Examination of cochlear tissue indicated that prestin chimeric mice demonstrate a mosaic in which mutant and normal OHCs interleave along the cochlear partition, similar to all other chimeric mouse models. The anatomical distribution of prestin-containing OHCs was compared with physiological data including thresholds and tuning curves for the compound action potential (CAP) recorded in anesthetized mice. Analysis of these measures did not reveal mixed phenotypes in which the distribution of prestin-containing OHCs impacted sensitivity and frequency selectivity to different degrees. However, by reducing the number of prestin-containing OHCs, phenotypes intermediate between WT and KO response patterns were obtained. Accordingly, we demonstrate a proportional reduction in sensitivity and in the tip length of CAP tuning curves as the number of OHCs derived from the KO genome increases; i.e., genotype ratio and phenotype are closely related.
Glutamate Controls Growth Rate and Branching of Dopaminergic Axons
Authors: Schmitz Yvonne , Luccarelli James , Kim Minji , Wang Mi , Sulzer David
Published: September 2009

Dopamine-releasing neurons of the substantia nigra pars compacta produce an extraordinarily dense and expansive plexus of innervation in the striatum converging with glutamatergic corticostriatal and thalamostriatal axon terminals at dendritic spines of medium spiny neurons. Here, we investigated whether glutamatergic signaling promotes arborization and growth of dopaminergic axons. In postnatal ventral midbrain cultures, dopaminergic axons rapidly responded to glutamate stimulation with accelerated growth and growth cone splitting when NMDA and AMPA/kainate receptors were activated. In contrast, when AMPA/kainate receptors were selectively activated, axon growth rate was decreased. To address whether this switch in axonal growth response was mediated by distinct calcium signals, we used calcium imaging. Combined NMDA and AMPA/kainate receptor activation elicited calcium signals in axonal growth cones that were mediated by calcium influx through L-type voltage-gated calcium channels and ryanodine receptor-induced calcium release from intracellular stores. AMPA/kainate receptor activation alone elicited calcium signals that were solely attributable to calcium influx through L-type calcium channels. We found that inhibitors of calcium/calmodulin-dependent protein kinases prevented the NMDA receptor-dependent axonal growth acceleration, whereas AMPA/kainate-induced axonal growth decrease was blocked by inhibitors of calcineurin and by increased cAMP levels. Our data suggest that the balance between NMDA and AMPA/kainate receptor activation regulates the axonal arborization pattern of dopamine axons through the activation of competing calcium-dependent signaling pathways. Understanding the mechanisms of dopaminergic axonal arborization is essential to the development of treatments that aim to restore dopaminergic innervation in Parkinson's disease.
Coding of Visual Space during Motor Preparation: Approaching Objects Rapidly Modulate Corticospinal Excitability in Hand-Centered Coordinates
Authors: Makin Tamar R. , Holmes Nicholas P. , Brozzoli Claudio , Rossetti Yves , Farnè Alessandro
Published: September 2009

Defensive behaviors, such as withdrawing your hand to avoid potentially harmful approaching objects, rely on rapid sensorimotor transformations between visual and motor coordinates. We examined the reference frame for coding visual information about objects approaching the hand during motor preparation. Subjects performed a simple visuomanual task while a task-irrelevant distractor ball rapidly approached a location either near to or far from their hand. After the distractor ball appearance, single pulses of transcranial magnetic stimulation were delivered over the subject's primary motor cortex, eliciting motor evoked potentials (MEPs) in their responding hand. MEP amplitude was reduced when the ball approached near the responding hand, both when the hand was on the left and the right of the midline. Strikingly, this suppression occurred very early, at 70–80 ms after ball appearance, and was not modified by visual fixation location. Furthermore, it was selective for approaching balls, since static visual distractors did not modulate MEP amplitude. Together with additional behavioral measurements, we provide converging evidence for automatic hand-centered coding of visual space in the human brain.
AMPA Receptor Ligand Binding Domain Mobility Revealed by Functional Cross Linking
Authors: Plested Andrew J. R. , Mayer Mark L.
Published: September 2009

Glutamate receptors mediate the majority of excitatory synaptic transmission in the CNS. The AMPA-subtype has rapid kinetics, with activation, deactivation and desensitization proceeding on the millisecond timescale or faster. Crystallographic, biochemical, and functional studies suggest that GluR2 Cys mutants which form intermolecular disulfide cross-links between the lower D2 lobes of the ligand binding cores can be trapped in a conformation that represents the desensitized state. We used multi-channel rapid perfusion techniques to examine the state dependence of cross-linking in these mutants. Under reducing conditions, both wild-type GluR2 and the G725C and S729C mutants have normal activation and desensitization kinetics, but the Cys mutants can be efficiently trapped in nonconducting states when oxidized. In contrast the I664C mutant is only partially inactivated under oxidizing conditions. For S729C, disulfide cross-links form rapidly when receptors are desensitized in the presence of glutamate, but receptors also become trapped at rest, in the absence of agonist. We assessed such spontaneous trapping in various conditions, including CNQX, a competitive antagonist; kainate, a weak partial agonist; or when desensitization was blocked by the L483Y mutation that stabilizes the D1 dimer interface. These experiments suggest that trapping in the absence of glutamate is due to two motions: Spontaneous breaking of the D1 dimer interface and hyperextension of the lower lobes of the ligand binding core. These data show that the glutamate binding domains are surprisingly mobile in the absence of ligand, which could influence receptor activity in the brain.
Description of anisotropically microstrain-broadened line profiles by Edgeworth series
Authors: Leineweber Andreas
Published: September 2009

The diffraction effects within the Stokes-Wilson approximation of a non-Gaussian microstrain distribution in a macroscopically isotropic specimen are described by anisotropic Edgeworth series. This Edgeworth series can for each reflection hkl be quantified by the 3rd, 4th ... N
th cumulants of the microstrain distribution projected on the reflection´s diffraction vector. The diffraction-vector (hkl) dependence of these N
th cumulants can be described by 2N
th-rank tensors which characterise the microstrain distribution in the crystal´s frame of reference. The situation considerably simplifies in the special case of univariateness of the microstrain distribution, leading to equal (or inverted) shapes of the line-broadening contribution due to microstrain for all different hkl reflections. The Edgeworth description of microstrain was applied to X-ray powder diffraction data of two slightly inhomogeneous hexagonal ε-iron-nitride powders, ε-FeN0.433 and ε-FeN0.407. The microstrain-like line-broadening data was evaluated in terms of the probability-density functions described by Edgeworth series for the composition of these two powders.
Structure determinations of three fluorescent organic pigments by powder diffraction and micro-crystal structure analysis
Authors: Brüning Jürgen , Alig Edith , Meents Alke , van de Streek Jacco , Schmidt Martin U.
Published: September 2009

Bisazomethine compounds with 2-hydroxynaphthalene moieties belong to the few organic pigments which show fluorescence in the solid state. The condensation products of hydrazine with 4-formyl-3-hydroxy-2-naphthoic acid-4′-methoxyanilide (C38H30N4O6), as well as the corresponding 4′-chloro and 2′,5′-dichloro derivatives (C36H24Cl2N4O4 and C36H22Cl4N4O4) are almost insoluble in all common solvents, even at temperatures of 200 °C. The 4′-methoxy derivative exists in at least two polymorphs. Small crystals of the a-phase could be obtained from N-methylpyrrolidone at 150 °C. A crystal with a size of just 1 × 2 × 10 μm3 was sufficient to determine the crystal structure by micro-focus synchrotron-X-ray diffraction. The phenyl groups are disordered.

The crystal structure of the β-phase of the 4′-methoxy derivative, as well as the structures of the two other derivatives were determined from X-ray powder diffraction data. The crystal structures were solved by real-space methods using the program DASH, the Rietveld refinement was done with the program TOPAS. The 2′,5′-dichloro derivative crystallises in P-1, Z = 1, all other phases in P21/c with Z = 2. All compounds form intramolecular hydrogen bonds, which explain the solid state fluorescence.
Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome
Authors: Pacifico Lucia , Poggiogalle Eleonora , Costantino Francesco , Anania Caterina , Ferraro Flavia , Chiarelli Francesco , Chiesa Claudio
Published: September 2009

Background

Ghrelin, a peptide mainly derived from the stomach, plays a pivotal role in the regulation of food intake, energy metabolism, and storage, as well as in insulin sensitivity. Ghrelin circulates in acylated (A-Ghr) and nonacylated (NA-Ghr) forms, and their potential differential associations with insulin resistance (IR) in childhood obesity remain undefined.

Objective

We investigated the associations of ghrelin forms with IR in normal weight and obese children and the impact of metabolic syndrome (MS) on their plasma values.

Design

A total of 210 children in four subgroups of normal weight/obese children with and without components of MS were studied. Fasting blood glucose, insulin, lipid profile, and acylated and total ghrelin were examined. IR was determined by a homeostasis model assessment (HOMA) of IR.

Results

In the entire population, plasma insulin and HOMA-IR were associated negatively with T-Ghr and NA-Ghr, but positively with the ratio of A/NA-Ghr after adjustment for age, gender, and Tanner stage. Obese metabolically abnormal children had lower T-Ghr and NA-Ghr, but comparable A-Ghr and a higher A/NA-Ghr ratio than obese metabolically normal subjects. Compared with lean healthy children, lean metabolically abnormal subjects had higher A-Ghr and the A/NA-Ghr ratio, but comparable T-Ghr and NA-Ghr. A multiple regression analysis showed that A-Ghr and the A/NA-Ghr ratios were positively associated with HOMA-IR, independent of age, gender, Tanner stage, and body mass index (or waist circumference) and other components of MS.

Conclusions

A-Ghr excess may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of IR and MS.
Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma
Authors: Hoftijzer Hendrieke , Heemstra Karen A , Morreau Hans , Stokkel Marcel P , Corssmit Eleonora P , Gelderblom Hans , Weijers Karin , Pereira Alberto M , Huijberts Maya , Kapiteijn Ellen , Romijn Johannes A , Smit Johannes W
Published: September 2009

Objective

Treatment options for patients with radioactive iodine (RaI) refractory metastases of differentiated thyroid carcinoma (DTC) are limited. We studied the effects of the multitarget tyrosine kinase inhibitor sorafenib on the reinduction of RaI uptake and tumor progression.

Design

Open, single center, single arm 26-week prospective phase II study with open-ended extension.

Methods

We treated 31 patients with progressive metastatic or locally advanced RaI refractory DTC with sorafenib 400 mg b.i.d. The primary endpoint was reinduction of RaI uptake at 26 weeks. Additional endpoints were the radiological response and the influence of bone metastases.

Results

At 26 weeks of sorafenib therapy, no reinduction of RaI uptake at metastatic sites was observed, but 19 patients (59%) had a clinical beneficial response, eight of whom had a partial response (25%) and 11 had stable disease (34%). Seven patients had progressive disease (22%). Sorafenib was significantly less effective in patients with bone metastases. The estimated median progression free survival was 58 weeks (95% confidence interval, CI, 47–68). In general, thyroglobulin (Tg) response (both unstimulated and TSH stimulated) reflected radiological responses. The median time of the nadir of Tg levels was 3 months. Responses were not influenced by histological subtype, mutational status or other variables. No unusual side effects were observed.

Conclusions

Sorafenib has a beneficial effect on tumor progression in patients with metastatic DTC, but was less effective in patients with bone metastases. Diagnostic whole body scintigraphy did not reveal an effect of sorafenib on the reinduction of RaI uptake.
Effects of Flaxseed Gum Addition and Drying Conditions on Creep-Recovery Properties and Water Vapour Transmission Rate of Starch-Based Films
Authors: Li Xin-yu , Wang Yong , Li Dong
Published: September 2009

This study investigated the effect of different concentrations of flaxseed gum (0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%) and various drying conditions (40 °C, 60 °C, 80 °C) on creep-recovery property and water vapor transmission rate (WVTR) of a starch-based films composed of cornstarch, flaxseed gum and glycerol. In creep-recovery tests, the data were modeled by Berger model. Results showed that E2 and ?1 of different flaxseed gum concentrations all decreased with an increase of flaxseed gum concentration first and then increased in both creep and recovery tests. Increasing drying temperature decreased E2 and ?1 in both creep and recovery tests. The addition of flaxseed gum increased WVTR compared with the flaxseed gum free sample. Films under different drying conditions displayed similar WVTR.
The effect of cholic acid treatment on the oxidative status of soybean plants
Authors: Kevresan Slavko , Malencic Djordje , Popovic Milan , Kuhajda Ksenija , Kandrac Julijan
Published: September 2009

The objective of this work was to study the effect of treatment of young soybean plants with cholic acid of different concentrations on their oxidative status. Young soybean plants, grown hydroponically for two weeks, were treated by adding cholic acid to the nutrient solution at the concentrations 20, 40, 60 and 80 mg/L, the control being without cholic acid. After one week, several parameters of the oxidative status were determined in the leaves and roots of the plants: contents of superoxide (-O?2 ), hydroxyl radicals (?OH) and glutathione (GSH), lipid peroxidation (LP), the superoxide dismutase (SOD) activity and the soluble protein accumulation, as well as the contents of chlorophylls and carotenoids. Treatments with cholic acid increased - O?2, LP, ?OH and GSH in the leaves of the treated plants, while only the OH content increased in the roots at higher cholic acid concentrations. The obtained results support the idea that cholic acid, as an elicitor of defense responses in plants, might act through the generation of an oxidative burst.
Studies on chromium(III) removal from aqueous solutions by sorption on Sphagnum moss peat
Authors: Balan Catalin , Bilba Doina , Macoveanu Matei
Published: September 2009

Batch sorption experiments were performed for the removal of chromium(III) ions from aqueous solutions using Romanian Sphagnum moss peat (untreated and treated with NaCl solution) as sorbent. In order to establish the best conditions for the sorption of chromium(III), the influence of initial pH, contact time, peat dose and metal ion concentration was investigated. The Freundlich, Langmuir and Dubinin-Radushkevich models were applied to describe the sorption isotherms and to calculate its constants. The experimental data fitted well to the Langmuir model with a maximum sorption capacity of 18.6 mg Cr(III)/g of peat. The mean free energy of sorption suggests that the binding of Cr(III) on peat occurred through an ion exchange mechanism. The kinetic data evaluated by pseudo-first order and pseudo-second order kinetic models showed that the sorption of chromium onto the peat followed a pseudo-second order rate equation. The chromium(III) could be easily eluted from the loaded peat using 0.10 M HCl and the peat may be reused in several sorption/ desorption cycles. The experimental results indicated the potential of Sphagnum moss peat for removal of Cr(III) from wastewaters.
Microstructure and properties of boronizing layer of Fe-based powder metallurgy compacts prepared by boronizing and sintering simultaneously
Authors: Dong X. , Hu J. , Huang Z. , Wang H. , Gao R. , Guo Z.
Published: September 2009

In this study, the boronized layers were formed on the surfaces of specimens with a composition of Fe-2 wt. % Cu-0.4 wt. % C by sintering and boronizing simultaneously, using a pack boronizing method. The processes were performed in the temperature range of 1050 - 1150 oC at a holding time of 4 hours in 97 % N2 and 3 % H2 atmosphere. Scanning electron microscopy examinations showed that the boronized layers formed on the surface of boronized and sintered specimens have a denticular morphology. The thicknesses of the boronized layers varied from 63 to 208 ?m depending on the processing temperature. The structures of the boronized layers were Fe2B and FeB confirmed by X-ray diffraction analysis. The microhardness values of boronized layers ranged from 1360 to 2066 HV0.3 much higher than that of substrate hardness which was about 186 HV0.3. Wear testing results showed that the wear resistance of the boronized and sintered specimens was significantly improved, resulting from increased surface microhardness.
The Use of Alteplase for Treatment of Occluded Central Venous Catheters in Home Care
Authors: Moureau Nancy , Mlodzik Lisa , Pool Susan Markel
Published: September 2009

Purpose. The purpose of this trial was to confirm safety and efficacy with thrombolytic use on complete and partially occluded central catheters using alteplase for the home care population. This trial attempts to provide additional evidence for the safe and effective use of a thrombolytic agent for catheter clearance, specifically with home care patients. Method. Patients were eligible for inclusion if (1) blood could not be withdrawn for partial occlusion or (2) blood could not be withdrawn and inability to flush presented with complete occlusion. Through an established Protocol, using the negative-pressure technique, nurses administered alteplase, 1mg/1 cc concentration, to home care patients who met inclusion criteria. Instillations were repeated at 20-minute intervals for up to three repetitions, if needed, with the third instillation remaining overnight. Results. Instillation of alteplase was successful in clearing catheter thrombotic occlusions in 66. 7% of patients studied in this outpatient population without thrombolytic events or drug related adverse effects. Conclusions. The authors confirm that catheter occlusions can be safely resolved in the alternate care/home care setting using established negative-pressure protocols. Although overnight dwell was used successfully and unsuccessfully in this trial without adverse effects, the small sample size does not Provide adequate definitive conclusions.
The Effect of Nursing Interventions on Catheter-related Bloodstream Infections in Patients Receiving Total Parenteral Nutrition Through Peripherally Inserted Central Catheter Lines
Authors: Sucy Sandra C. , Hupka Dennis , Curchoe Ruth
Published: September 2009

Background: Catheter-related blood-stream infection (CRBSI) is a serious and costly complication associated with central venous catheters. Nursing interventions that focus on decreasing bacterial colonization at the insertion site could decrease infection rates. Method: This retrospective study examined CRBSI in patients requiring peripherally inserted central catheters (PICCs) for total parenteral nutrition. One hundred and ninety-two patients with 235 catheters and an average dwell time of 11.5 days participated. Nursing interventions included a chlorhexidine-impregnated sponge dressing and a double skin scrub prior to insertion. Conclusion: The results of the study show that the interventions did not reduce CRBSI in the target population but the double skin scrub did decrease CRBSI in the general PICC population.
Reduction of Malposition in Peripherally Inserted Central Catheters With Tip Location System
Authors: Naylor Christine L.
Published: September 2009

Catheter malposition is a common occurrence with the insertion of peripherally inserted central catheters (PICCs). Santa Rosa Memorial Hospital (SRMH) in Santa Rosa, California, trialed and implemented a new tip location device to evaluate whether malposition rates could be reduced. This article compares 6 months of data. Three of these months were compiled before using the tip locator device. The right atrial malposition rate remained consistent at 18% with or without the use of the tip locator device. All other malpositions were 13.4% without use of the tip locator. The overall malposition rate was 2.5% with the use of the tip locator device. By using this technology, supply and labor costs were reduced, as were referrals to interventional radiology and delays in treatment. Overall staff satisfaction improved.
Practice, Standards of Care, and Strategies to Prevent Infection: A Review of Flushing Solutions and Injection Caps (Part 3 of a 3-Part Series)
Authors: Richardson Deborah K.
Published: September 2009

This is Part 3 of a 3-part series and will review flushing solutions and injection caps in addition to practice issues, standards, guidelines, and preventive strategies developed to prevent or decrease infections of central venous catheters.
Taking the Leap From PICC Placement to Tip Placement
Authors: Royer Timothy , Earhart Ann
Published: September 2009

Nurses who place peripherally inserted central catheters (PICCs) obtain x-rays after placement to determine tip placement. Radiologists read and interpret the x-ray to verify tip placement. It is then the primary physician or the radiologist who releases the PICC line for use. Until 2002, there were few institutions across the United States that empowered the vascular access nurse to take on this responsibility. This article discusses how to advance practice at the state-board-of-nursing level and discusses strategies to implement the change in scope of practice.
In Vitro Antimicrobial Effectiveness of 5 Catheter Insertion-Site Dressings
Authors: Bhende Shubhangi , Rothenburger Stephen
Published: September 2009

Polyurethane foam dressing impregnated with chlorhexidine gluconate was compared with 4 silver dressings for antimicrobial efficacy. Efficacy of antimicrobial dressings was evaluated using zone of inhibition assay against 7 clinically relevant bacteria and yeast. The test was carried out for up to 7 consecutive days by transferring the dressings daily. Microbiocidal activity exhibited by different dressings within the zone of inhibition was also evaluated as a part of the study. Three silver dressings were similar to each other in performance and had different patterns of efficacy varying from days 1 to 6 than the chlorhexidine dressing. A hydrogel dressing containing silver performed poorly compared to all other dressings. The study results indicated that the antimicrobial dressing impregnated with chlorhexidine gluconate had excellent antimicrobial activity and showed sustained efficacy for a period of 7 days.
Achieving Zero Catheter Related Blood Stream Infections: 15 Months Success in a Community Based Medical Center
Authors: Harnage Sophie A.
Published: September 2009

Achieving Zero Catheter Related Blood Stream Infections: 15 Month Success In A Community Based Medical Center. Background and Purpose: Catheter related blood stream infection (CRBSI) is a major cause of patient morbidity, mortality, and cost. Lower CRBSI rates would decrease inpatient length of stay. Project: An innovative central line bundle was developed to reduce CRBSI. An innovative combination of focused nursing practice and product technologies were selected for the bundle and implemented through a defined educational program. Data was collected from thirty-two critical care beds: 16 medical/surgical ICU and 16 Trauma-Neuro ICU beds. Results: From January 2006 thru March 2007 there were Zero occurrences of CRBSI. Over this 15 month period our PICC insertions increased by 103%, and our interventional radiology referral rate decreased to less than 2%. Implications/Conclusions: A multimodality bundle, combining nursing practice interventions and technology can successfully decrease the incidence of CRBSI. While some of the bundle components have not been widely researched and instead are based on theory or accepted clinical practice, the early outcome provides a basis for additional study and refinement. It also invites research into the various components of the bundle to evaluate the effect each separate practice and product lends to its success.
The Right Mediastinal Border and Central Venous Anatomy on Frontal Chest Radiograph—Direct CT Correlation
Authors: Verhey Peter T. , Gosselin Marc V. , Primack Steven L. , Blackburn Paul L. , Kraemer Alexander C.
Published: September 2009

We describe a direct and accurate method for defining chest radiographic anatomy and use this method to delineate the anatomic composition of the right mediastinal border in an adult population. Intravenous contrast-enhanced computed tomographic scans of the chest and accompanying scout tomograms from 99 adults without previously known or detected cardiopulmonary disease that could potentially distort mediastinal, cardiac, or pulmonary anatomy were retrospectively evaluated. Transverse CT images through the mediastinum were directly referenced to the respective acquisition location on the scout tomogram via the acquisition reference line. The anatomic composition of the right mediastinal border on the scout tomogram was determined by drawing a vertical line tangential to the most lateral right mediastinal structure in each transverse CT image. The lengths and relationships of these structures were tabulated. These results will help to create a consensus among radiologists and other clinicians regarding radiographic anatomy, allowing improved localization of mediastinal pathology and enabling more optimal positioning of vascular and cardiac support devices.
Low-End Videoconferencing for Vascular Access Device Site Assessment in Homecare
Authors: Astapova Elena V. , Stachura Max E. , Chernecky Cynthia , Rosenkoetter Marlene M.
Published: September 2009

Vascular access devices (VAD) represent high technology and are used frequently in infant, pediatric, adult, and geriatric populations for vascular infusion of chemotherapy, immunotherapy, blood products, biologic response modifiers, nutrition support, analgesics, ionotropics, antibiotics, and other medications, as well as for extraction of pleural fluid from patients with chronic effusions and for treatment with dialysis. Increasingly, these devices are migrating to the home setting as they are used in chronic care and as insurance requirements reduce access to prolonged hospital stays.

Surveillance of infections in high risk patients such as those with cancer, cardiac conditions, or post-trauma convalescence is essential to avoid adverse events and to offer early treatment. VAD site and blood stream infections are common VAD complications, occurring in up to 50% of home care patients, usually during days 4–25 after hospital discharge. Our literature search for reports of remote home monitoring for support of VAD patients and their caregivers found none.

The use of videoconferencing technology to assess VAD sites in the post-discharge environment would significantly enhance patient safety, facilitate continuity of care, and meet the Communicable Disease Center's stated need for the development of surveillance systems to monitor infections in home care settings. Low-cost Internet- or telephone-based videoconferencing technology that could be deployed easily and used during risk periods would be highly beneficial to patients and increase the cost-effective use of homecare nursing personnel.

We report criteria-based protocols for remote assessment of VAD status, for monitoring VAD care procedures employed in the home, and for conducting VAD-care teaching of patients and their caregivers. In addition, we report an initial evaluation of the ability to assess VAD status using low-end videoconferencing technologies.
Improving Safety for Nurses Providing IV Therapy
Authors: Baker Brenda
Published: September 2009

Objectives: The risk nurses face related to exposure to blood borne pathogens associated with IV therapy are daily challenges. Providing a product with the least risk of exposure is the responsibility of the healthcare organization. Where the two meet creates an environment that fosters a safe work environment and raises the awareness that safety is everyone's job.

Project: Following identification of exposure rates from IV catheter stylets the Carilion Clinic undertook a project to improve the practices and provide a higher level of safety for its staff.

Results: Following staff evaluation and selection of a new IV catheter, the exposure rate related to contaminated IV catheter stylets dropped from 13 in 2005 to 2 in 2007. Numerous other practices and products related to IV therapy were reviewed and improved upon following the catheter conversion as well.

Conclusion and Implications for Practice: A higher level of safety can be achieved when nurses are involved in the selection of a product, staff education, and support from leadership.
Difficult Peripheral Venous Access: Recognizing and Managing the Patient at Risk
Authors: Walsh Gabrielle
Published: September 2009

Nurses commonly face challenges placing peripheral intravenous (IV) lines in adults and children, a situation described as difficult venous access (DVA). Multiple venipuncture attempts can heighten patient anxiety and suffering, delay vital treatment, and increase costs. Numerous factors such as small, fragile or hidden veins can predispose patients to DVA, and collapsed veins due to dehydration are especially problematic. Several techniques can improve venous prominence, but when IV access cannot be achieved promptly, other routes of administration can be valuable. For rehydration fluids and certain drugs, subcutaneous administration may be a safe and effective alternative, providing cost and ease-of-use advantages.
Teaching Students about Intravenous Therapy: Increased Competence and Confidence
Authors: Jensen Rebecca
Published: September 2009

Aim/Purpose: Graduate nurses require competency in IV therapy. Associate Degree in Nursing (ADN) programs offer elective IV education to provide additional information for interested students. After instituting such a course, students' perceived comfort and knowledge of IV therapy were evaluated.

Review of Relevant Literature: Studies demonstrated that IV education for nurses in practice helped reduce complication rates. Dated research also indicated that nursing programs were reluctant to provide IV instruction that included advanced skills, such as catheter insertions. More recent literature involved teaching methodology.

Methods: A researcher-designed survey was distributed at the completion of an ADN program to evaluate perceived knowledge and comfort related to IV therapy, as well as information about IV education throughout the program.

Results: Students who participated in the workshop perceived having a higher level of comfort and knowledge of several IV content areas than those who participated in the course or had no elective IV education. Conversely, participants in the workshop and course felt more comfortable with central line dressing changes and IV insertions than students who did not take either IV educational offering.

Conclusions: The standard IV education appeared to provide adequate knowledge and comfort with IV therapy. However, optional IV education benefited students who wanted more in depth IV knowledge and skills.

Implications for Practice: The best methods for teaching ADN students about IV therapy remains unknown. However, offering an elective course provides opportunities for interested students to increase their knowledge and comfort related to IV therapy prior to graduation.
A Clinical Trial of a New All-in-One Peripheral Short Catheter
Authors: McNeill Elizabeth E. , Hines Nicole L , Phariss Regina
Published: September 2009

The objectives of this survey were to: 1) understand current peripheral IV stabilization practices within our hospital and 2) evaluate the use of a new closed IV catheter system with a built-in stabilization platform. All medical-surgical patients within an 851-bed acute care hospital with peripheral-short catheters were evaluated within a 3-day period for catheter securement, dwell time, and signs of complications. Additionally, catheter restart data were collected from a renal telemetry unit for 2 weeks. Catheter and dressing protocols were then standardized to a new catheter system with a built-in stabilization platform (Nexiva™ Closed Catheter System) and an absorbent transparent dressing (SorbaView® 2000). After a 2-week trial of the new protocol, catheters were again evaluated for securement and restart data were again collected from the renal telemetry unit. Staff nurse (N = 42) opinions on the new catheter system and dressing combination were sought, as well as a vote on willingness to change to the new catheter system and dressing. Results demonstrate improvement in catheter stabilization (out to 96 hours of dwell-time), decreased restarts, a high clinical preference for the new catheter/dressing system, and a high willingness to convert to the new system. Results indicate that the new closed IV catheter system with a built-in stabilization platform and the transparent absorbent dressing evaluated in this survey may help to improve catheter securement and increase dwell-time. Research studies utilizing more rigorous randomized, controlled comparisons are warranted.
Structural control of englacial conduits in the temperate Matanuska Glacier, Alaska, USA
Authors: Gulley Jason
Published: September 2009

Fourteen englacial conduits were mapped within 2 km of the terminus of the temperate Matanuska Glacier, Alaska, USA, to ice depths of 65 m using speleological techniques. Detailed three-dimensional maps of the conduits were made over 3 years to characterize conduit relationships with glacier structural features and to track conduit evolution through time. All conduits consisted of single unbranching passages that followed fractures in the ice. All conduits were either too constricted to continue or became water-filled at their deepest explored point and were not able to be followed to the glacier bed. Conduit morphology varied systematically with the orientation of the glacier principal stresses, allowing them to be categorized into two broad classes. The first class of conduits were formed by hydrostatic crevasse penetration where a large supraglacial stream intersected longitudinal crevasses. These conduits plunged toward the glacier bed at angles of 30–40°. The second class of conduits formed where smaller streams sank into the glacier on shear crevasses. Many of these conduits changed direction dramatically where they intersected transverse crevasses at depth. These results suggest that the conduits observed in this study formed along fractures and, over their surveyed length, were not affected by gradients in ice overburden pressure.
Snow replica method for three-dimensional X-ray microtomographic imaging
Authors: Heggli Martin , Frei Esther , Schneebeli Martin
Published: September 2009

Visualization and quantification of snow structures at a scale of a few millimetres is important in understanding the mechanical, thermal and electromagnetic properties of snow. Surface sections and, to an even greater degree, three-dimensional (3-D) reconstructions of cast snow samples are difficult to prepare, and automatic image processing is notoriously difficult and often requires manual evaluation. Here, we present a new method to measure the 3-D structure of cast snow samples. Snow samples cast with diethyl phthalate (DEP) and frozen are cut to a sample size a few centimetres in diameter and up to 10 cm in height. The ice of these samples is then sublimated in high vacuum and the remaining negative structure (replica) is imaged using X-ray microtomography (micro-CT). The accuracy of the method is demonstrated by comparing micro-CT scans of the original snow structure and the replica. The method described here allows easy transportation of samples, requires little manual interaction, has a very high spatial resolution of up to 10 μm and is environmentally friendly.
Effect of Quercetin on Paraoxonase 2 Levels in RAW264.7 Macrophages and in Human Monocytes—Role of Quercetin Metabolism
Authors: Boesch-Saadatmandi Christine , Pospissil Renata Toedter , Graeser Anne-Christin , Canali Raffaella , Boomgaarden Inka , Doering Frank , Wolffram Siegfried , Egert Sarah , Mueller Manfred James , Rimbach Gerald
Published: September 2009

There is increasing evidence that the intracellular antioxidant enzyme paraoxonase 2 (PON2) may have a protective function in the prevention of atherogenesis. An enhancement of PON2 activity by dietary factors including flavonoids is therefore of interest. In the present study we determined the effect of quercetin on paraoxonase 2 levels in cultured murine macrophages in vitro and in overweight subjects with a high cardiovascular risk phenotype supplemented with 150 mg quercetin/day for 42 days in vivo. Supplementation of murine RAW264.7 macrophages in culture with increasing concentrations of quercetin (1, 10, 20 μmol/L) resulted in a significant increase in PON2 mRNA and protein levels, as compared to untreated controls. Unlike quercetin, its glucuronidated metabolite quercetin-3-glucuronide did not affect PON2 gene expression in cultured macrophages. However the methylated quercetin derivative isorhamnetin enhanced PON2 gene expression in RAW264.7 cells to similar extent like quercetin. Although supplementing human volunteers with quercetin was accompanied by a significant increase in plasma quercetin concentration, dietary quercetin supplementation did not change PON2 mRNA levels in human monocytes in vivo. Current data indicate that quercetin supplementation increases PON2 levels in cultured monocytes in vitro but not in human volunteers in vivo.
Excavatoids E and F: Discovery of Two New Briaranes from the Cultured Octocoral Briareum excavatum
Authors: Sung Ping-Jyun , Chen Bo-Yuan , Lin Mei-Ru , Hwang Tsong-Long , Wang Wei-Hsien , Sheu Jyh-Horng , Wu Yang-Chang
Published: September 2009

Two new briarane-related diterpenoids, designated as excavatoids E (1) andF (2), were isolated from the cultured octocoral Briareum excavatum. The structures ofcompounds 1 and 2 were established on the basis of extensive spectral data analysis. Briaranes 1 and 2 were found to exhibit moderate inhibitory effects on elastase release by human neutrophils.