bluuebunny/crossref_metadata_2025 huggingface dataset:
MAGNETIC PROPERTIES AND INDUCTION HEATING OF NiZn FERRITE NANOPARTICLES
Authors: JIAO QIGANG , ZHANG YI , ZHAI YA , BAI XIAOJUN , ZHANG WEI , DU JUN , ZHAI HONGRU
Published: June 2008

A series of nanoparticle powders of Ni x Zn 1-x Fe 2 O 4 (x = 0, 0.30, 0.40, 0.50, 0.55, 0.60, 0.70 and 1.0) ferrites was synthesized by the refluxing method at relatively low temperatures. The average size of nanoparticles is about 20 nm. The magnetic properties and induction heating behavior were investigated. On increasing the Ni content, x, from 0 to 0.50, the saturation magnetization and permeability increased, and then decreased with further increasing Ni content with the bulk Ni – Zn ferrite. The maximum value of magnetization was about 50 emu/g near x = 0.50, where the induction heating rate and induction heating final temperature of the ferrite-water suspension also showed maximum values. The specific absorption rate obtained from the initial induction heating rate curve was found to be linearly proportional to the square of the alternating magnetic field, which is roughly consistent with the theoretical power loss of magnetic materials in the alternating field.
Active Rab11 and functional recycling endosome are required for E-cadherin trafficking and lumen formation during epithelial morphogenesis
Authors: Desclozeaux Marion , Venturato Juliana , Wylie Fiona G. , Kay Jason G. , Joseph Shannon R. , Le Huong T. , Stow Jennifer L.
Published: June 2008

The correct targeting and trafficking of the adherens junction protein epithelial cadherin (E-cadherin) is a major determinant for the acquisition of epithelial cell polarity and for the maintenance of epithelial integrity. The compartments and trafficking components required to sort and transport E-cadherin to the basolateral cell surface remain to be fully defined. On the basis of previous data, we know that E-cadherin is trafficked via the recycling endosome (RE) in nonpolarized and newly polarized cells. Here we explore the role of the RE throughout epithelial morphogenesis in MDCK monolayers and cysts. Time-lapse microscopy in live cells, altering RE function biochemically, and expressing a dominant-negative form of Rab11 (DN-Rab11), each showed that the RE is always requisite for E-cadherin sorting and trafficking. The RE remained important for E-cadherin trafficking in MDCK cells from a nonpolarized state through to fully formed, polarized epithelial monolayers. During the development of epithelial cysts, DN-Rab11 disrupted E-cadherin targeting and trafficking, the subapical localization of pERM and actin, and cyst lumen formation. This final effect demonstrated an early and critical interdependence of Rab11 and the RE for E-cadherin targeting, apical membrane formation, and cell polarity in cysts.
Intracellular Mg2+ is a voltage-dependent pore blocker of HCN channels
Authors: Vemana Sriharsha , Pandey Shilpi , Larsson H. Peter
Published: June 2008

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization that creates time-dependent, inward rectifying currents, gated by the movement of the intrinsic voltage sensor S4. However, inward rectification of the HCN currents is not only observed in the time-dependent HCN currents, but also in the instantaneous HCN tail currents. Inward rectification can also be seen in mutant HCN channels that have mainly time-independent currents ( 5 ). In the present study, we show that intracellular Mg2+ functions as a voltage-dependent blocker of HCN channels, acting to reduce the outward currents. The affinity of HCN channels for Mg2+ is in the physiological range, with Mg2+ binding with an IC50 of 0.53 mM in HCN2 channels and 0.82 mM in HCN1 channels at +50 mV. The effective electrical distance for the Mg2+ binding site was found to be 0.19 for HCN1 channels, suggesting that the binding site is in the pore. Removing a cysteine in the selectivity filter of HCN1 channels reduced the affinity for Mg2+, suggesting that this residue forms part of the binding site deep within the pore. Our results suggest that Mg2+ acts as a voltage-dependent pore blocker and, therefore, reduces outward currents through HCN channels. The pore-blocking action of Mg2+ may play an important physiological role, especially for the slowly gating HCN2 and HCN4 channels. Mg2+ could potentially block outward hyperpolarizing HCN currents at the plateau of action potentials, thus preventing a premature termination of the action potential.
Connexin45 is expressed in the juxtaglomerular apparatus and is involved in the regulation of renin secretion and blood pressure
Authors: Hanner Fiona , von Maltzahn Julia , Maxeiner Stephan , Toma Ildiko , Sipos Arnold , Krüger Olaf , Willecke Klaus , Peti-Peterdi János
Published: June 2008

Connexin (Cx) proteins are known to play a role in cell-to-cell communication via intercellular gap junction channels or transiently open hemichannels. Previous studies have identified several connexin isoforms in the juxtaglomerular apparatus (JGA), but the vascular connexin isoform Cx45 has not yet been studied in this region. The present work aimed to identify in detail the localization of Cx45 in the JGA and to suggest a functional role for Cx45 in the kidney using conditions where Cx45 expression or function was altered. Using mice that express lacZ coding DNA under the control of the Cx45 promoter, we observed β-galactosidase staining in cortical vasculature and glomeruli, with specific localization to the JGA region. Renal vascular localization of Cx45 was further confirmed with the use of conditional Cx45-deficient (Cx45fl/fl:Nestin-Cre) mice, which express enhanced green fluorescence protein (EGFP) instead of Cx45 only in cells that, during development, expressed the intermediate filament nestin. EGFP fluorescence was found in the afferent and efferent arteriole smooth muscle cells, in the renin-producing juxtaglomerular cells, and in the extra- and intraglomerular mesangium. Cx45fl/fl:Nestin-Cre mice exhibited increased renin expression and activity, as well as higher systemic blood pressure. The propagation of mechanically induced calcium waves was slower in cultured vascular smooth muscle cells (VSMCs) from Cx45fl/fl:Nestin-Cre mice and in control VSMC treated with a Cx45 gap mimetic peptide that inhibits Cx45 gap junctional communication. VSMCs allowed the cell-to-cell passage of the gap junction permeable dye Lucifer yellow, and calcium wave propagation was not altered by addition of the ATP receptor blocker suramin, suggesting that Cx45 regulates calcium wave propagation via direct gap junction coupling. In conclusion, the localization of Cx45 to the JGA and functional data from Cx45fl/fl:Nestin-Cre mice suggest that Cx45 is involved in the propagation of JGA vascular signals and in the regulation of renin release and blood pressure.
Enhanced amiloride-sensitive superoxide production in renal medullary thick ascending limb of Dahl salt-sensitive rats
Authors: O'Connor Paul M. , Lu Limin , Schreck Carlos , Cowley Allen W.
Published: June 2008

The aims of the present study were to determine whether superoxide (O2−) production is enhanced in medullary thick ascending limb (mTAL) of Dahl salt-sensitive (SS) rats compared with a salt-resistant consomic control strain (SS.13BN) and to elucidate the cellular pathways responsible for augmented O2−production. Studies were carried out in 7- to 10-wk-old male SS and SS.13BNrats fed either a 0.4% NaCl diet or a 4.0% NaCl diet for 3 days before tissue harvest. Tissue strips containing mTAL were isolated from the left kidney, loaded with the O2−-sensitive fluorescent dye dihydroethidium, superfused with modified Hanks’ solution, and imaged at ×60 magnification on a heated microscope stage. O2−production was stimulated in mTAL by incrementing superfusate NaCl concentration from 154 to 254 to 500 mM. O2−production was enhanced in mTAL of SS rats compared with SS.13BNrats in response to incrementing bath NaCl. Addition of N-methyl-amiloride (100 μM) or inhibition of NAD(P)H oxidase reduced O2−production in SS mTAL to levels observed in SS.13BNrats. Both amiloride- and ouabain-sensitive pathways of O2−production were elevated following 3 days of high (4.0%) NaCl feeding in mTAL of SS and SS.13BNrats. We conclude that mTAL from SS rats exhibit enhanced amiloride-sensitive O2−production. The amiloride-sensitive O2−response in mTAL is independent of active Na+transport and appears to be mediated by NAD(P)H oxidase. Amiloride-sensitive O2−production is likely to contribute to augmented outer medullary O2−production observed in SS rats during both normal and high NaCl diets.
Dietary salt induces transcription of the prostaglandin transporter gene in renal collecting ducts
Authors: Chi Yuling , Pucci Michael L. , Schuster Victor L.
Published: June 2008

Prostaglandin E2(PGE2) plays an important role in maintaining body fluid homeostasis by activating its receptors on the renal collecting duct (CD) to stimulate renal Na+and water excretion. The PG carrier prostaglandin transporter (PGT) is expressed on the CD apical membrane, where it mediates PG reuptake as part of the termination of autocrine PG signaling. Here we tested the hypothesis that dietary salt loading regulates PGT gene transcription in renal CDs. We placed green fluorescence protein (GFP) under control of 3.3 kb of the mouse PGT promoter and injected this construct into the pronuclei of fertilized FVB mouse eggs. Four of thirty-eight offspring were GFP positive by genotyping. We extensively characterized one (no. 29) PGT-GFP transgenic mouse line. On microscopic examination, GFP was expressed in CDs as determined by their expression of aquaporin-2. We fed mice a low (0.03% NaCl)-, normal (0.3% NaCl)-, or high-salt (3% NaCl) diet for 2 wk and quantified CD GFP expression. The average number of GFP-positive CD cells per microscopic section varied directly with dietary salt intake. Compared with mice on the control (0.3% sodium) diet, mice on a low-sodium (0.03%) diet had reduced numbers of GFP-positive cells (71% of control, P < 0.001), whereas mice on a high-sodium (3%) diet had increased numbers of GFP-positive cells (139% of control, P < 0.001). This increase in apparent CD PGT transcription resulted in a 51–55% increase ( P < 0.001) in whole kidney PGT mRNA levels as determined by real-time PCR. The regulation of PG signal termination via reuptake represents a new pathway for controlling renal Na+balance.
Renal Na+-K+-Cl−cotransporter activity and vasopressin-induced trafficking are lipid raft-dependent
Authors: Welker Pia , Böhlick Alexandra , Mutig Kerim , Salanova Michele , Kahl Thomas , Schlüter Hartmut , Blottner Dieter , Ponce-Coria Jose , Gamba Gerardo , Bachmann Sebastian
Published: June 2008

Apical bumetanide-sensitive Na+-K+-2Cl−cotransporter (NKCC2), the kidney-specific member of a cation-chloride cotransporter superfamily, is an integral membrane protein responsible for the transepithelial reabsorption of NaCl. The role of NKCC2 is essential for renal volume regulation. Vasopressin (AVP) controls NKCC2 surface expression in cells of the thick ascending limb of the loop of Henle (TAL). We found that 40–70% of Triton X-100-insoluble NKCC2 was present in cholesterol-enriched lipid rafts (LR) in rat kidney and cultured TAL cells. The related Na+-Cl−cotransporter (NCC) from rat kidney was distributed in LR as well. NKCC2-containing LR were detected both intracellularly and in the plasma membrane. Bumetanide-sensitive transport of NKCC2 as analyzed by86Rb+influx in Xenopus laevis oocytes was markedly reduced by methyl-β-cyclodextrin (MβCD)-induced cholesterol depletion. In TAL, short-term AVP application induced apical vesicular trafficking along with a shift of NKCC2 from non-raft to LR fractions. In parallel, increased colocalization of NKCC2 with the LR ganglioside GM1 and their polar translocation were assessed by confocal analysis. Apical biotinylation showed twofold increases in NKCC2 surface expression. These effects were blunted by mevalonate-lovastatin/MβCD-induced cholesterol deprivation. Collectively, these findings demonstrate that a pool of NKCC2 distributes in rafts. Results are consistent with a model in which LR mediate polar insertion, activity, and AVP-induced trafficking of NKCC2 in the control of transepithelial NaCl transport.
α2-Adrenergic agonists protect against radiocontrast-induced nephropathy in mice
Authors: Billings F. T. , Chen Sean W. C. , Kim Mihwa , Park Sang Won , Song Joseph H. , Wang Shuang , Herman Joseph , D'Agati Vivette , Lee H. Thomas
Published: June 2008

Radiocontrast nephropathy (RCN) is a common clinical problem for which there is no effective therapy. Utilizing a murine model, we tested the hypothesis that α2-adrenergic receptor agonists (clonidine and dexmedetomidine) protect against RCN induced with iohexol (a nonionic low-osmolar radiocontrast). C57BL/6 mice were pretreated with saline, clonidine, or dexmedetomidine before induction of RCN. Some mice were pretreated with yohimbine (a selective α2-receptor antagonist) before saline, clonidine, or dexmedetomidine administration. α2-Agonist-treated mice had reduced plasma creatinine, renal tubular necrosis, renal apoptosis, and renal cortical proximal tubule vacuolization 24 h after iohexol injection. Yohimbine reversed the protective effects of clonidine and dexmedetomidine pretreatment. Injection of iohexol resulted in a rapid (∼90 min) fall of renal outer medullary blood flow. Clonidine and dexmedetomidine pretreatment significantly attenuated this perfusion decrease without changing systemic blood pressure. To determine whether proximal tubular α2-adrenergic receptors mediate the cytoprotective effects, we treated cultured human proximal tubule (HK-2) cells and rat pulmonary microvascular endothelial cells with iohexol after vehicle, clonidine, or dexmedetomidine pretreatment. Iohexol caused a direct dose-dependent reduction of HK-2 and rat pulmonary microvascular endothelial cell viability, but α2-agonists failed to preserve the viability of both cell types. We conclude that α2-adrenergic receptor agonists protect mice against RCN by preserving outer medullary renal blood flow. As α2-agonists are widely utilized during the perioperative period, our findings may have significant clinical relevance to improving outcomes following radiocontrast exposure.
Finite element 3D reconstruction of the pulmonary acinus imaged by synchrotron X-ray tomography
Authors: Tsuda A. , Filipovic N. , Haberthür D. , Dickie R. , Matsui Y. , Stampanoni M. , Schittny J. C.
Published: June 2008

The alveolated structure of the pulmonary acinus plays a vital role in gas exchange function. Three-dimensional (3D) analysis of the parenchymal region is fundamental to understanding this structure-function relationship, but only a limited number of attempts have been conducted in the past because of technical limitations. In this study, we developed a new image processing methodology based on finite element (FE) analysis for accurate 3D structural reconstruction of the gas exchange regions of the lung. Stereologically well characterized rat lung samples ( Pediatr Res 53: 72–80, 2003) were imaged using high-resolution synchrotron radiation-based X-ray tomographic microscopy. A stack of 1,024 images (each slice: 1024 × 1024 pixels) with resolution of 1.4 μm3 per voxel were generated. For the development of FE algorithm, regions of interest (ROI), containing ∼7.5 million voxels, were further extracted as a working subunit. 3D FEs were created overlaying the voxel map using a grid-based hexahedral algorithm. A proper threshold value for appropriate segmentation was iteratively determined to match the calculated volume density of tissue to the stereologically determined value ( Pediatr Res 53: 72–80, 2003). The resulting 3D FEs are ready to be used for 3D structural analysis as well as for subsequent FE computational analyses like fluid dynamics and skeletonization.
Substantia Nigra Stimulation Influences Monkey Superior Colliculus Neuronal Activity Bilaterally
Authors: Liu Ping , Basso Michele A.
Published: June 2008

The inhibitory drive arising from the basal ganglia is thought to prevent the occurrence of orienting movements of the eyes, head, and body in monkeys and other mammals. The direct projection from the substantia nigra pars reticulata (SNr) to the superior colliculus (SC) mediates the inhibition. Since the original experiments in the SNr of monkeys the buildup or prelude neuron has been a focus of SC research. However, whether the SNr influences buildup neurons in SC is unknown. Furthermore, a contralateral SNr–SC pathway is evident in many species but remains unexplored in the alert monkey. Here we introduced electrical stimulation of one or both SNr nuclei while recording from SC buildup neurons. Stimulation of the SNr reduced the discharge rate of SC buildup neurons bilaterally. This result is consistent with activation of an inhibitory drive from SNr to SC. The time course of the influence of ipsilateral SNr on the activity of most SC neurons was longer (∼73 ms) than the influence of the contralateral SNr (∼34 ms). We also found that the variability of saccade onset time and saccade direction was altered with electrical stimulation of the SNr. Taken together our results show that electrical stimulation activates the inhibitory output of the SNr that in turn, reduces the activity of SC buildup neurons in both hemispheres. However, rather than acting as a gate for saccade initiation, the results suggest that the influence of SNr inhibition on visually guided saccades is more subtle, shaping the balance of excitation and inhibition across the SC.
Cold Stimuli Evoke Potentials That Can Be Recorded Directly From Parasylvian Cortex in Humans
Authors: Greenspan J. D. , Ohara S. , Franaszczuk P. , Veldhuijzen D. S. , Lenz F. A.
Published: June 2008

Anatomic, imaging, and lesion studies suggest that insular or parietal opercular cortical structures mediate the sensation of nonpainful cold. We have now tested the hypothesis that cold stimuli evoke electrical responses from these cortical structures in humans. We recorded the response to cold stimuli from electrodes implanted directly over parasylvian cortex for the investigation of intractable seizures. The results demonstrate that slow potentials can be evoked consistently over structures adjacent to the sylvian fissure in response to nonpainful cold. The polarity of these cold evoked potentials (EPs) for electrodes above the sylvian fissure is opposite to those below. These results suggest that the generator of cold EPs is close to the sylvian fissure in the parietal operculum or insula.
A comparative study of Rietveld phase analysis of cement clinker using neutron, laboratory X-ray, and synchrotron data
Authors: Peterson Vanessa K. , Ray Abhi S. , Hunter Brett A.
Published: June 2008

Rietveld refinement using neutron, laboratory X-ray, and synchrotron powder diffraction data of NIST SRM clinker 8488 was performed. Quantitative phase analysis (QPA) results were compared between data, and with other studies. QPA results for the main phases in the clinker were found to be in agreement between the different data used here, and in and other studies, although the QPA of the tricalcium silicate polymorphs was shown to be inconsistent. The QPA results for the tricalcium aluminate phase varied between data types, and the neutron data were unable to distinguish this phase.
Combined elastic strain and macroscopic stress characterization in polycrystalline Cu thin films
Authors: Eiper E. , Martinschitz K. J. , Keckes J.
Published: June 2008

This work introduces a new simple approach to determine experimental X-ray elastic constants (XECs) of thin films by coupling the sin2ψ method and the substrate curvature technique. The approach is demonstrated on polycrystalline Cu thin films with the thickness 200, 800, and 2400 nm deposited on Si(100) substrates. Applying synchrotron radiation, the elastic strains in the films are determined using sin2ψ method while the macroscopic stresses are assessed by measuring the substrate curvature. The stresses are calculated using the Stoney formula from the radius of substrate curvature determined by the rocking curve measurement of substrate 400 reflection at different sample positions. Results show that the magnitude of the macroscopic stress in the films is proportional to the magnitude of the slope in the sin2ψ plots. On the basis of this observation, XECs of the films were calculated showing no dependence on the film thickness. The characterization of the samples was performed at the synchrotron source Hasylab.
X-ray powder diffraction data and crystal data of polymorphic form 2 of carnidazole
Authors: de Armas Hector Novoa , Peeters Oswald M. , Blaton Norbert , De Ridder Dirk J. A. , Schenk Henk
Published: June 2008

The indexed powder diffraction pattern and related crystallographic data for polymorphic form 2 of carnidazole (C8H12N4O3S) are reported, as a first step in the structure determination by powder diffraction methods. The unit cell dimensions were determined from high resolution synchrotron powder diffraction data (λ=0.079 998 0 nm) and evaluated by indexing programs. The monoclinic cell found for this polymorph isa=1.3908(2) nm,b=08094(2) nm,c=1.0645(2) nm,β=110.82(2)°,V=1.12015(27)nm3,Z=4,Dx=1.445 Mg∕m3.
Powder X-ray diffraction and Rietveld analysis of La1−xCaxMnO3(0<X<1)
Authors: Sagdeo P. R. , Anwar Shahid , Lalla N. P.
Published: June 2008

Single-phase samples of La1−xCaxMnO3compounds have been synthesized by solid-state reaction. Detailed Rietveld analysis of powder X-ray diffraction data showed that La1−xCaxMnO3undergoes a structural phase transformation fromR-3ctoPnmaatX=0.05–0.075. There is a linear variation of lattice parameters as a function of calcium concentration. The slope of this linear variation changes atX=0.6. A correlation between observed Mn-O bond lengths, corresponding to different compositions, and possible magnetic phases is discussed.
Refined ettringite (Ca6Al2(SO4)3(OH)12∙26H2O) structure for quantitative X-ray diffraction analysis
Authors: Goetz-Neunhoeffer F. , Neubauer J.
Published: June 2008

A revised structure model of ettringite is presented, in order to provide quantitative X-ray diffraction (QXRD) of this mineral in cement pastes. The model is derived from two different existing structure models, both of which are suitable for restricted use but are inferior to the refined ettringite structure presented. In the first published ettringite structure proposed by Moore and Taylor [Acta Crystallogr. B 26, 386–393 (1970)], none of the 128 positions for H are given in the unit cell, which results in reduced scattering power for use of this model for quantification purposes. For the precise quantification of ettringite in samples together with anhydrous phases, the scattering factors of all atoms including the H positions are indispensable. The revised structure model is based on the data of Moore and Taylor, supplemented by the H positions determined by Berliner (Material Science of Concrete Special Volume, The Sydney Diamond Symposium, American Ceramic, Society, 1998, pp. 127–141) on the basis of a neutron diffraction structural investigation of deuterated ettringite at 20 K. Berliner’s (Material Science of Concrete Special Volume, The Sydney Diamond Symposium, American Ceramic Society, 1998, pp. 127–141) thermal parameter should not, however, be used, since a normal application is at room temperature. In order further to improve the structure model of ettringite, Rietveld refinement with the rigid body approach for OH and H2O molecules and SO4 tetrahedra was employed. The refined and improved ettringite structure model was tested for quantitative phase analysis by the determination of actual ettringite contents in mixtures with an internal standard. Synthesized and orientation-free prepared ettringite powders were investigated by X-ray powder diffraction analysis and quantified in four different blends with zircon. The quantification results with the new structure model demonstrate the superior quality of the revised ettringite structure.
Magnetic structure refinement with neutron powder diffraction data using GSAS: A tutorial
Authors: Cui J. , Huang Q. , Toby B. H.
Published: June 2008

Neutron diffraction provides a direct probe for the ordering of spins from unpaired electrons in materials with magnetic properties. The ordering of the spins can be modeled in many cases by adding spin directions to standard crystallographic models. This requires, however, that crystallographic space groups be extended by addition of a “color” attribute to symmetry operations, which determines if the operation maintains or flips the direction of a magnetic spin. Rietveld analysis provides a mechanism for fitting magnetic structure models to powder diffraction data. The general structure and analysis system (GSAS) software suite is commonly used for Rietveld analysis and includes the ability to compute magnetic scattering. Different approaches are commonly used within GSAS to create models that include magnetism. Three equivalent but different approaches are presented to provide a tutorial on how magnetic scattering data may be modeled using differing treatment of symmetry. Also discussed is how magnetic models may be visualized. The commands used to run the GSAS programs are summarized within, but are shown in great detail in supplementary web pages.
Six Years Follow‐up of the Levels of TNF‐α and IL‐6 in Patients with Complex Regional Pain Syndrome Type 1
Authors: Wesseldijk Feikje , Huygen Frank J. P. M. , Heijmans-Antonissen Claudia , Niehof Sjoerd P. , Zijlstra Freek J.
Published: June 2008

In an earlier study, levels of the proinflammatory cytokines TNF‐α and IL‐6 are higher in blisters fluid from the complex regional pain syndrome type 1 (CRPS1) side obtained at 6 and 30 months (median) after the initial event. The aim of this follow‐up study is to determine the involvement of these cytokines in long lasting CRPS1. Twelve CRPS1 patients, with median disease duration of 72 months, participated. The levels of TNF‐α and IL‐6 were measured in blister fluid; disease activity was reevaluated by measuring pain and differences in temperature, volume, and mobility between both extremities. Differences in levels of IL‐6 and TNF‐α and mobility between both sides were significantly decreased. Pain and differences in temperature and volume were not significantly altered. No correlation was found between the cytokines and the disease characteristics. These results indicate that IL‐6 and TNF‐α are only partially responsible for the signs and symptoms of CRPS1.
Preclinical Evidence for the Benefits of Penile Rehabilitation Therapy following Nerve-Sparing Radical Prostatectomy
Authors: Albersen M. , Joniau S. , Claes H. , Van Poppel H.
Published: June 2008

Erectile dysfunction following radical prostatectomy remains a frequent problem despite the development of nerve-sparing techniques. This erectile dysfunction is believed to be neurogenic, enhanced by hypoxia-induced structural changes which result in additional veno-occlusive dysfunction. Recently, daily use of intracavernous vasoactive substances and oral use of PDE5-inhibitors have been clinically studied for treatment of postprostatectomy erectile dysfunction. Since these studies showed benefits of “penile rehabilitation therapy,” these effects have been studied in a preclinical setting. We reviewed experimental literature on erectile tissue preserving and neuroregenerative treatment strategies, and found that preservation of the erectile tissue by the use of intracavernous nitric oxide donors or vasoactive substances, oral PDE5-inhibitors, and hyperbaric oxygen therapy improved erectile function by antifibrotic effects and preservation of smooth muscle. Furthermore, neuroregenerative strategies using neuroimmunophilin ligands, neurotrophins, growth factors, and stem cell therapy show improved erectile function by preservation of NOS-containing nerve fibers.
Production of L‐Leucine Nanoparticles under Various Conditions Using an Aerosol Flow Reactor Method
Authors: Lähde Anna , Raula Janne , Kauppinen Esko I.
Published: June 2008

We have studied the formation of L‐leucine nanoparticles under various conditions using an aerosol flow reactor method. Temperatures and L‐leucine concentrations for the experiments were selected to vary the saturation conditions for L‐leucine in the reactor. In the two extreme cases, L‐leucine is either in (i) the condensed phase (110 ∘C) or completely in (ii) the vapour phase (200 ∘C) for all concentrations; (iii) at the intermediate temperature (150 ∘C), the extent of evaporation of L‐leucine depends notably on the concentration, and thus partial evaporation and production of residual particles are expected. The size distribution of particles and the particle morphology varied according to formation mechanism with the geometric mean diameter of the particles between 30 nm and 210 nm. Hollow, spherical particles were obtained with the droplet‐to‐particle method without vaporisation of L‐leucine; whereas leafy‐looking particles were produced by homogeneous nucleation of supersaturated L‐leucine vapour and subsequent growth by heterogeneous vapour deposition.
Intratumoral Estrogens and Estrogen Receptors in Human Non–Small Cell Lung Carcinoma
Authors: Niikawa Hiromichi , Suzuki Takashi , Miki Yasuhiro , Suzuki Satoshi , Nagasaki Shuji , Akahira Junichi , Honma Seijiro , Evans Dean B. , Hayashi Shin-ichi , Kondo Takashi , Sasano Hironobu
Published: June 2008

Purpose: The possible involvement of gender-dependent factors has been suggested in human non-small cell lung carcinomas (NSCLC), but their precise roles remain largely unclear. Therefore, we examined intratumoral estradiol concentrations in NSCLC to examine local actions of estrogens in NSCLC.

Experimental Design: Fifty-nine frozen specimens of NSCLC were available for liquid chromatography/electrospray tandem mass spectrometry to study intratumoral estradiol concentrations. In addition, A549 NSCLC cells stably expressing estrogen receptor (ER) α (A549 + ERα) or ERβ (A549 + ERβ) were used in vitro studies.

Results: Forty-three (73%) of 59 NSCLC showed higher concentration of estradiol in carcinoma tissues than the corresponding nonneoplastic lung tissues from the same patient, and intratumoral estradiol concentrations were significantly (P = 0.0002 and 2.2-fold) higher than the corresponding nonneoplastic lungs. The intratumoral concentration of estradiol was positively correlated with aromatase expression, tumor size, and Ki-67 status in ERα- or ERβ-positive cases. In in vitro studies, estradiol significantly increased cell proliferation of A549 + ERα or A549 + ERβ, which was significantly suppressed by selective ER modulators, tamoxifen or raloxifene. Both A549 + ERα and A549 + ERβ cells expressed aromatase. The cell proliferation level in these cells was significantly increased under treatment with testosterone, and it was inhibited by addition of the aromatase inhibitor letrozole.

Conclusions: These results suggest that estradiol is locally produced in NSCLC mainly by aromatase and plays an important role in the growth of ERα- or ERβ-positive NSCLC. Therefore, use of selective ER modulators and/or aromatase inhibitors may be clinically effective in NSCLC that are positive for both ER and aromatase.
Expression of t-DARPP Mediates Trastuzumab Resistance in Breast Cancer Cells
Authors: Belkhiri Abbes , Dar Altaf A. , Peng Dun Fa , Razvi Mohammad H. , Rinehart Cammie , Arteaga Carlos L. , El-Rifai Wael
Published: June 2008

Purpose: We have investigated the role of t-DARPP in trastuzumab resistance in ERBB2-amplified and overexpressed breast cancer cell lines.

Experimental Design: We have used the HR-5 and HR-6 trastuzumab-resistant cells that were established from tumors that recurred in the presence of trastuzumab therapy following xenografts of BT-474 cells in nude mice. In addition, SKBR-3 cells, engineered for stable expression of t-DARPP, and HCC-1569 cells, which have constitutive expression of t-DARPP and are de novo resistant to trastuzumab, were used.

Results: We reported ≥15-fold up-regulation of mRNA and protein levels of t-DARPP in HR-5 and HR-6 cells compared with their progenitor BT-474 trastuzumab-sensitive cells. The t-DARPP expression was not regulated by changes in its promoter DNA methylation levels. The SKBR-3 cells stably expressing t-DARPP developed resistance to trastuzumab compared with their parental cells and empty vector controls (P < 0.01). The trastuzumab-resistant cell lines showed a significant increase in pAKT (Ser473) and BCL2 protein levels. The small interfering RNA knockdown of t-DARPP in all trastuzumab-resistant cells led to a significant reduction in ERBB2, pAKT (Ser473), and BCL2 protein levels with a significant decrease in cell viability (P ≤ 0.001) and an increase in cleaved caspase-3 levels, indicating the progression of these cells toward apoptosis. The t-DARPP protein was associated with both heat shock protein 90 and ERBB2 forming a potential protein complex. This association may play a role in regulating ERBB2 protein in trastuzumab-resistant cells.

Conclusion: We conclude that t-DARPP is a novel molecular target that can mediate the therapeutic resistance to trastuzumab in breast cancer cells.
Atherothrombosis and Plaque Heterology: Different Location or a Unique Disease?
Authors: Slevin M. , Wang Q. , Font M. Angels , Luque A. , Juan-Babot Oriol , Gaffney J. , Kumar P. , Kumar S. , Badimon L. , Krupinski J.
Published: June 2008

Formation of unstable plaques frequently results in atherothrombosis, the major cause for ischaemic stroke, myocardial infarction and peripheral arterial disease. Patients who have symptomatic thrombosis in one vascular bed are at increased risk of disease in other beds. However, the development of the disease in carotid, coronary and peripheral arteries may have different pathophysiology suggesting that more complex treatment protocols may have to be designed to reduce plaque development at different locations. In this review we describe the known risk factors, compare the developmental features of coronary and carotid plaque development and determine their association with end-point ischaemic events. Differences are also seen in the genetic contribution to plaque development as well as in the deregulation of gene and protein expression and cellular signal transduction activity of active cells in regions susceptible to thrombosis. Differences between carotid and coronary artery plaque development might help to explain the differences in anatomopathological appearance and risk of rupture.
Linoleic-Acid-Induced Growth Suppression Induces Quiescent Cancer Cell Nests in Nude Mice
Authors: Ohmori Hitoshi , Sasahira Tomonori , Fujii Kiyomu , Yi Luo , Shimomoto Takasumi , Kuniyasu Hiroki
Published: June 2008

We examined the effect of linoleic acid (LA) on tumor formation. Cell growth was suppressed by LA in a dose-dependent manner in MKN28 and Colo320 cells. Continuous treatment with LA provided growth arrest in both cells at 5–7 weeks after the treatment. LA-pretreated MKN28 and Colo320 cells showed higher tumorigenicity (9/10 and 10/10, respectively) than nontreated cells (2/10 and 3/10, respectively; p < 0.01) in nude mice. In contrast, LA-pretreated MKN28 and Colo320 cells showed more suppressed tumor growth than nontreated cells (p < 0.01). LA-pretreated MKN28 and Colo320 cells with LA administration after the inoculation did not form macroscopic tumors. Histological examination revealed small cancer cell aggregations, which showed no proliferative activity. In LA-treated MKN28 and Colo320 cells, protein production of Bcl-2 was increased, whereas Bak, EGFR and VEGF levels were decreased. These findings suggest that LA might induce quiescence and subsequent dormancy in cancer cells.
Expression of RUNX3 Gene, Methylation Status and Clinicopathological Significance in Breast Cancer and Breast Cancer Cell Lines
Authors: Jiang Ying , Tong Dandan , Lou Ge , Zhang Ying , Geng Jingshu
Published: June 2008

Background: Runt-related transcription factor 3 (RUNX3) is a novel tumor suppressor gene that is frequently silenced by promoter hypermethylation in gastric cancer. In this study, we aimed to analyze the methylation status of the RUNX3 promoter in breast cancer and to evaluate the relationship between RUNX3 expression and breast carcinogenesis and prognosis. Methods: RT-PCR and Western blot were applied on 5 breast cancer cell lines, the human normal breast cell line Hs578Bst and 30 pairs of breast cancer and their matching normal breast tissues to detect mRNA and protein expression of the RUNX3 gene. Methylation-specific PCR was employed to detect the methylation status of the RUNX3 promoter. Immunohistochemical study was performed to analyze RUNX3 protein expression in 88 breast cancer tissues and 40 breast fibroadenomas. Results: The expression of RUNX3 mRNA and protein were negative in 3 breast cancer cell lines (T47D, MCF7 and SKBR3) as analyzed by RT-PCR and Western blotting. Hypermethylation of the RUNX3 promotor was identified in the T47D and MCF7 cell lines, but was not detected in SKBR3. Western blot analysis showed that the RUNX3 protein of 44 kDa was detected in 15 of 30 (50%) breast cancers. However, RUNX3 protein was detected in all normal breast tissues. Methylation was detected in 13 of the 15 tissues (86.67%) that did not express RUNX3 protein, but was never detected in any surrounding normal tissues. Immunohistochemistry results revealed that the positive rate of RUNX3 protein expression in breast cancer (35.23%) was much lower than that in breast fibroadenoma (85%). RUNX3 expression was correlated with tumor infiltration, clinical stage, lymph node metastasis and the expression of estrogen and progesterone receptor (p < 0.05), but was not related to age, tumor types and pathological grade (p > 0.05). The survival rate of the patients with RUNX3-positive expression was higher than that with RUNX3-negative expression (p < 0.05). Conclusions: The expression of RUNX3 gene is decreased in breast cancer. The RUNX3 gene may play an important role in the carcinogenesis of breast cancer. The mechanism of its inactivation may be hypermethylation of the promoter. With the increased progression of breast cancer, the expression of RUNX3 protein tends to decrease. The expression of RUNX3 protein has a definite value in judging prognosis in breast cancer.
Tako-Tsubo-Like Cardiomyopathy: Specific ECG Findings, Characterization and Clinical Findings in a European Single Center
Authors: von Korn Hubertus , Yu Jiangtao , Lotze Ulrich , Ohlow Marc-Alexander , Huegl Burkhard , Schulte Walter , Haberl Kai , Wagner Andreas , Gruene Stefan , Lauer Bernward
Published: June 2008

Objectives: A newly discovered heart syndrome mimicking acute coronary syndrome has been termed ‘Tako-Tsubo cardiomyopathy’ (TTC). Differentiation from acute myocardial infarction using the ECG is an important issue in clinical practice. Methods: We retrospectively analyzed patients admitted for cardiac catheterization between September 2003 and September 2006. Results: From 26,593 cardiac catheterization procedures, we identified 21 patients with suggested TTC (0.08%). Trigger mechanisms were present in 38.1%; all patients had elevated troponin levels (mean 3.9 ng/ml). Median age was 68.4 years; 90.5% were female. Hypertension was seen in 85.7% and atrial fibrillation in 19.1%. Specific ECG findings related to a TTC are: a mild elevation of the ST segment arising from the S curve of the QRS complex, where the maximum ST segment elevation at the basis of the T wave is <1.5 mm, T-wave inversion, absence of ST segment depression and a summated amplitude of the S curve in V1 plus R in V6 <1.5 mV. An intraventricular gradient was seen in 9.5%; coronary atherosclerosis was detected in 57.1%. Follow-Up Data: Mean follow-up was 13.2 months. 47.6% were free from angina or dyspnea, most of the patients received β-blockers/ACE inhibitors (76.2%). One patient had a sudden cardiac death (4.8%), 1 patient became an implantable cardioverter-defibrillator primarily due to resuscitation. Conclusion: TTC is a rare syndrome mimicking acute coronary syndrome that shows a specific ECG pattern and does not appear to be an unambiguously benign disease.
Endothelin-1 Gene Variant Lys198Asn and Plasma Endothelin Level in Obstructive Sleep Apnea
Authors: Diefenbach Konstanze , Kretschmer Kathrin , Bauer Steffen , Malzahn Uwe , Penzel Thomas , Roots Ivar , Fietze Ingo
Published: June 2008

Obstructive sleep apnea (OSA) is a recognized risk factor for cardiovascular disorders. Thus, an association between endothelin-1 (EDN1) and OSA can be assumed. We investigated a cohort of 364 consecutive patients (age 57 ± 10 years) with mild to severe OSA for the EDN1 variant Lys198Asn (G/T) and endothelin plasma levels and compared them with 57 controls. The Lys198Asn genotype was significantly associated with the apnea/hypopnea index (AHI) with a median of 30/h of sleep for GG, 27/h for GT and 59/h for TT genotype (p < 0.05). Further stratification of patients into 2 groups by body mass index (BMI) revealed a strong association between AHI and Lys198Asn polymorphism in 191 obese patients (p = 0.005), whereas in 173 nonobese patients, we observed no association. A substantial effect by BMI on OSA severity was seen with multiple linear regression (p < 0.001). However, this effect was modified by the Lys198Asn polymorphism and by gender: the AHI increase per unit of BMI was more pronounced in males than in females, and about 1.3 times greater in homozygous carriers of the mutant allele than in other carrier groups. EDN1 plasma levels of untreated OSA patients and of patients treated with nasal continuous positive airway pressure were not elevated compared with controls. Our results indicate that the Lys198Asn polymorphism is associated with the severity of OSA in obese subjects. The EDN1 plasma level cannot be used as a marker for OSA or its severity.
Long-Term Follow-Up of Patients with Relatively High Effective Defibrillation Threshold during Cardioverter Defibrillator Implantation with Endocardial Leads
Authors: Rosenheck Shimon , Sharon Zehava , Weiss Alexey
Published: June 2008

Objective: We evaluated the 15-year outcome of patients with an implantable cardioverter defibrillator (ICD) and a relatively high defibrillation threshold (DFT). Methods: After ICD implantation, patients were allocated to 3 groups: DFT 24–25 J (16 patients), effective defibrillation with 18–20 J (20 patients) and DFT <15 J (118 patients). An abbreviated DFT test was used during the implantation. The follow-up duration was 15.5 years. Results: There was no significant difference between the survivals of the 3 groups, with a mean survival of 7.30 ± 4.51 years. In the ventricular fibrillation zone, 99.69, 100 and 100% of the episodes were successfully defibrillated in the 3 groups, respectively. In the ventricular tachycardia zone, 83.24, 92.86 and 95.39% of the episodes were terminated with pacing therapy. The small differences between the groups were not statistically significant. The testing method did not have an impact on survival or therapy success rate. Conclusions: A 24-joule DFT with a 10-joule safety window is safe during 15 years of follow-up.
High Tofu Intake Is Associated with Worse Memory in Elderly Indonesian Men and Women
Authors: Hogervorst E. , Sadjimim T. , Yesufu A. , Kreager P. , Rahardjo T.B.
Published: June 2008

Background/Aims: Cell culture studies suggest that phytoestrogens, abundant in soy products such as tempe and tofu, could protect against cognitive decline. Paradoxically, the Honolulu Asia Aging Study reported an increased risk for cognitive impairment and other dementia markers with high tofu (soybean curd) intake. Methods: A cross-sectional study was carried out in 2 rural sites (Borobudur and Sumedang) and 1 urban site (Jakarta) among mainly Javanese and Sundanese elderly (n = 719, 52–98 years of age). Memory was measured using a word learning test sensitive to dementia and soy consumption was assessed using Food Frequency Questionnaire items. Results: High tofu consumption was associated with worse memory (β = –0.18, p < 0.01, 95% CI = –0.34 to –0.06), while high tempe consumption (a fermented whole soybean product) was independently related to better memory (β = 0.12, p < 0.05, 95% CI = 0.00–0.28), particularly in participants over 68 years of age. Fruit consumption also had an independent positive association. The analyses were controlled for age, sex, education, site and intake of other foods. Conclusion: The results for tofu consumption as a risk factor for low memory function may tie in with the Honolulu Asia Aging Study data. It is unclear whether these negative associations could be attributed to potential toxins or to its phytoestrogen levels. Estrogen (through which receptors phytoestrogens can exert effects) was found to increase dementia risk in women over 65 years of age. Tempe contains high levels of phytoestrogens, but (due to fermentation) also exhibits high folate levels which may exert protective effects. Future studies should validate these findings and investigate potential mechanisms.
Correlation between Loss of Bcl-XL Expression and Improved Prognosis in Advanced Esophageal Cancer Treated by Preoperative Chemoradiotherapy
Authors: Okumura M. , Kajiyama Y. , Takeda K. , Okumura K. , Tsurumaru M.
Published: June 2008

We investigated the clinical significance of the apoptosis- related molecule expression of tumor cells in patients with advanced esophageal cancer treated with preoperative chemoradiotherapy (CRT). Preoperative CRT reduced Bcl-XL expression in a significant proportion of the group responding to CRT but not in the group resisting CRT, although Bcl-2 expression was reduced in both groups. The mean survival time of the patients with cancers that lost Bcl-XL following CRT was significantly longer compared to those with cancers expressing Bcl-XL. These results suggested that CRT reduced Bcl-XL expression, and this decrease closely correlated with the prolonged survival of advanced esophageal cancer patients treated with preoperative CRT.
Post-Treatment Outcomes of Buprenorphine Detoxification in Community Settings: A Systematic Review
Authors: Horspool Michelle J. , Seivewright Nicholas , Armitage Christopher J. , Mathers Nigel
Published: June 2008

A systematic review was undertaken to examine studies of buprenorphine detoxification that has included post-treatment outcomes as well as more immediate aspects of progress. Studies were required to report details of buprenorphine withdrawal regime and post-treatment outcomes including abstinence rates. Only five studies met these criteria, with buprenorphine regimes lasting 3 days to several weeks, and with variable follow-up. Detoxification completion rates were 65–100%, but relatively few treatment completers were then drug free at their follow-up appointments. In subsequent prescribing, more patients had returned to opioid maintenance than complied with naltrexone. Our preliminary review indicates that buprenorphine is a suitable medication for the process of opiate detoxification but that this newer treatment option has not led to higher rates of abstinence following withdrawal. Further studies are required to more substantially examine abstinence outcomes, as well as characteristics which predict success.
From the Office to the Pub: The Role of Smoking-Relevant Contexts and Cue-Elicited Urge to Smoke
Authors: Thewissen Roy , van der Meijden Valerie A.F. , Havermans Remco C. , van den Hout Marcel , Jansen Anita
Published: June 2008

The present study investigates how environmental contexts can affect cue-elicited urge to smoke. A total of 33 smokers were repeatedly presented with a cue predicting smoking and a cue predicting no smoking in one room and the effect of context change in a different room was assessed. Results endorsed earlier findings that a cue predicting smoking availability elicited more urge to smoke than a cue predicting smoking unavailability. Furthermore, this study shows that a context switch from a low smoking-relevant room to a high smoking-relevant room reduces the learned differential urge responding between the two availability cues. These findings are discussed in relation to the role that smoking-relevant contexts play in the generalization of differential urge responding after a context switch. Furthermore, implications for government policies on smoking and clinical issues are discussed.