bluuebunny/crossref_metadata_2025 huggingface dataset:
Curcumin in inflammatory diseases
Authors: Shehzad Adeeb , Rehman Gauhar , Lee Young Sup
Published: December 2012

Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non‐toxic, and mediates its anti‐inflammatory effects through the down‐regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor‐mediated pathways, as well as activation of caspase cascades. In the current study, the anti‐inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. © 2012 BioFactors, 39(1):69–77, 2013
Luminal accumulation of newly synthesized morphine‐3‐glucuronide in rat liver microsomal vesicles
Authors: Révész Katalin , Tóth Blanka , Staines Adam G. , Coughtrie Michael W. H. , Mandl József , Csala Miklós
Published: December 2012

Morphine is converted to morphine 3‐β‐D‐glucuronide (M3G) by the UDP‐glucuronosyltransferase Ugt2b1 in the endoplasmic reticulum (ER) of rat liver. Because of its luminal localization, UGT activity requires UDP‐glucuronate import and glucuronide export across the ER membrane. The former transport is generally considered to be rate limiting and to explain the latency of UGT activities in intact microsomal vesicles. However, some observations indicate that the release of bulky glucuronides, such as M3G, might also be rate limiting for glucuronidation. This assumption was tested by characterizing the transport of M3G and its distribution between the intra‐ and extravesicular spaces during synthesis in rat liver microsomes. The amount of vesicle‐associated M3G was measured using rapid filtration and LC‐MS measurement. Our results reveal a remarkable accumulation of newly synthesized M3G in the microsomal lumen above the equilibrium. The transport showed a linear concentration‐dependence in a wide range (5–200 μM). Therefore, the build‐up of high (about 20 μM) luminal M3G concentration could adjust the rate of release to that of synthesis (44.85 ± 4.08 pmol/min/mg protein) during the conjugation of 100 μM morphine. These data can explain earlier findings indicative of separate intracellular pools of M3G in rat liver. Accumulation of bulky glucuronides in the ER lumen might also play an important role in their targeting and in the control of biliary excretion. © 2012 BioFactors, 2013
Transulnar carotid artery stent placement
Authors: Fang Hsiu‐Yu , Wang Yan , Zheng Jiang‐Tao , Wu Chiung‐Jen
Published: December 2012

Carotid artery stenting (CAS) has increased in popularity as an alternative to carotid artery endarterectomy for the treatment of significant carotid artery stenosis. The access site is predominantly the femoral artery, with radial or brachial access used less often. Here, we describe a case of CAS after failure of brachial access. Transulnar CAS was performed successfully without complications. Transulnar access represents an additional option in a patient undergoing CAS when conventional femoral, brachial, and radial arteries are not applicable. © 2012 Wiley Periodicals, Inc.
Flow Chemistry Syntheses of Styrenes, Unsymmetrical Stilbenes and Branched Aldehydes
Authors: Bourne Samuel L. , O'Brien Matthew , Kasinathan Sivarajan , Koos Peter , Tolstoy Päivi , Hu Dennis X. , Bates Roderick W. , Martin Benjamin , Schenkel Berthold , Ley Steven V.
Published: December 2012

Two tandem flow chemistry processes have been developed. A single palladium‐catalysed Heck reaction with ethylene gas provides an efficient synthesis for functionalised styrenes. Through further elaboration the catalyst becomes multi‐functional and performs a second Heck reaction providing a single continuous process for the synthesis of unsymmetrical stilbenes. In addition, the continuous, rhodium‐catalysed, hydroformylation of styrene derivatives with syngas affords branched aldehydes with good selectivity. Incorporation of an in‐line aqueous wash and liquid–liquid separation allowed for the ethylene Heck reaction to be telescoped into the hydroformylation step such that a single flow synthesis of branched aldehydes directly from aryl iodides was achieved. The tube‐in‐tube semi‐permeable membrane‐based gas reactor and liquid–liquid separator both play an essential role in enabling these telescoped flow processes.
A Pilot‐Scale System for Carbon Molecular Sieve Hollow Fiber Membrane Manufacturing
Authors: Karvan O. , Johnson J. R. , Williams P. J. , Koros W. J.
Published: December 2012

Carbon molecular sieve (CMS) membranes offer advantages over traditional polymeric membrane materials, but scale‐up of manufacturing systems has not received much attention. In the recent decade, there has been a dramatic increase in fundamental research on these materials with a variety of applications being studied. The results from a pilot‐scale CMS production system are presented. This system was designed based on extensive laboratory research, and hollow fiber membranes produced in this system show similar performance compared to membranes produced using a smaller bench‐scale system. After optimizing the system design, a 93 % recovery of the precursor fibers for use in membrane module preparation were obtained.
Ruthenium Complexes with Hydrophobic Ligands That Are Key Factors for the Optical Imaging of Physiological Hypoxia
Authors: Komatsu Hirokazu , Yoshihara Kazuki , Yamada Hisatsugu , Kimura Yu , Son Aoi , Nishimoto Sei‐ichi , Tanabe Kazuhito
Published: December 2012

The phosphorescence emission of ruthenium complexes was applied to the optical imaging of physiological hypoxia. We prepared three complexes with hydrophobic substituents on the phenanthroline ligand and characterized their emission, which was quenched by molecular oxygen. Among the complexes synthesized in this study, a pyrene chromophore‐linked ruthenium complex, Ru‐Py, exhibited optimal properties for the imaging of hypoxia; the prolonged lifetime of the triplet excited state of the ruthenium chromophore, which was induced by efficient energy distribution and transfer from the pyrene unit, provided the highest sensitivity towards molecular oxygen. The introduction of hydrophobic pyrene increased the lipophilicity of the complex, leading to enhanced cellular uptake. Consequently, the bright phosphorescence of Ru‐Py was seen in the cytoplasm of viable hypoxic cells, whereas the signal from aerobic cells was markedly weaker. Thus, we could clearly discriminate between hypoxic and aerobic cells by monitoring the phosphorescence emission. Furthermore, Ru‐Py was applied to optical imaging in live mice. An intramuscular injection of Ru‐Py successfully visualized ischemia‐based hypoxia, which was constructed by leg banding.
MRI contrast variation of thermosensitive magnetoliposomes triggered by focused ultrasound: a tool for image‐guided local drug delivery
Authors: Lorenzato Cyril , Cernicanu Alexandru , Meyre Marie‐Edith , Germain Matthieu , Pottier Agnès , Levy Laurent , de Senneville Baudouin Denis , Bos Clemens , Moonen Chrit , Smirnov Pierre
Published: December 2012

Improved drug delivery control during chemotherapy has the potential to increase the therapeutic index. MRI contrast agent such as iron oxide nanoparticles can be co‐encapsulated with drugs in nanocarrier liposomes allowing their tracking and/or visualization by MRI. Furthermore, the combination of a thermosensitive liposomal formulation with an external source of heat such as high intensity focused ultrasound guided by MR temperature mapping allows the controlled local release of the content of the liposome. MRI‐guided high‐intensity focused ultrasound (HIFU), in combination represents a noninvasive technique to generate local hyperthermia for drug release. In this study we used ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) encapsulated in thermosensitive liposomes to obtain thermosensitive magnetoliposomes (TSM). The transverse and longitudinal relaxivities of this MRI contrast agent were measured upon TSM membrane phase transition in vitro using a water bath or HIFU. The results showed significant differences for MRI signal enhancement and relaxivities before and after heating, which were absent for nonthermosensitive liposomes and free nanoparticles used as controls. Thus, incorporation of USPIO as MRI contrast agents into thermosensitive liposomes should, besides TSM tumor accumulation monitoring, allow the visualization of TSM membrane phase transition upon temperature elevation. In conclusion, HIFU under MR image guidance in combination with USPIO‐loaded thermosensitive liposomes as drug delivery system has the potential for a better control of drug delivery and to increase the drug therapeutic index. Copyright © 2012 John Wiley & Sons, Ltd.
Real‐time high‐resolution magnetic resonance tracking of macrophage subpopulations in a murine inflammation model: a pilot study with a commercially available cryogenic probe
Authors: Faraj Achraf Al , Luciani Nathalie , Kolosnjaj‐Tabi Jelena , Mattar Essam , Clement Olivier , Wilhelm Claire , Gazeau Florence
Published: December 2012

Macrophages present different polarization states exhibiting distinct functions in response to environmental stimuli. However, the dynamic of their migration to sites of inflammation is not fully elucidated. Here we propose a real‐time in vivo cell tracking approach, using high‐resolution (HR)‐MRI obtained with a commercially available cryogenic probe (Cryoprobe™), to monitor trafficking of differently polarized macrophages after systemic injection into mice. Murine bone marrow‐derived mononuclear cells were differentiated ex vivo into nonpolarized M0, pro‐inflammatory M1 and immunomodulator M2 macrophage subsets and labeled with citrate‐coated anionic iron oxide nanoparticles (AMNP). These cells were subsequently intravenously injected to mice bearing calf muscle inflammation. Whole body migration dynamics of macrophage subsets was monitored by MRI at 4.7 T with a volume transmission/reception radiofrequency coil and macrophage infiltration to the inflamed paw was monitored with the cryogenic probe, allowing 3D spatial resolution of 50 µm with a scan time of only 10 min. Capture of AMNP was rapid and efficient regardless of macrophage polarization, with the highest uptake in M2 macrophages. Flow cytometry confirmed that macrophages preserved their polarization hallmarks after labeling. Migration kinetics of labeled cells differed from that of free AMNP. A preferential homing of M2‐polarized macrophages to inflammation sites was observed. Our in vivo HR‐MRI protocol highlights the extent of macrophage infiltration to the inflammation site. Coupled to whole body imaging, HR‐MRI provides quantitative information on the time course of migration of ex vivo‐polarized intravenously injected macrophages. Copyright © 2012 John Wiley & Sons, Ltd.
Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical treatment of patients with indeterminate thyroid nodules
Authors: Kleiman David A. , Sporn Matthew J. , Beninato Toni , Crowley Michael J. , Nguyen Anvy , Uccelli Alessia , Scognamiglio Theresa , Zarnegar Rasa , Fahey Thomas J.
Published: December 2012

BACKGROUND:

Preoperative B‐type Raf kinase Val600Glu mutation, or BRAF(V600E), analysis has been proposed as a tool to guide initial surgery for indeterminate thyroid nodules. This study sought to determine if cytologic markers of malignancy are associated with the BRAF(V600E) mutation and if preoperative BRAF(V600E) testing would alter the initial management of patients with indeterminate nodules.

METHODS:

Patients who underwent surgery for a thyroid nodule between 2003 and 2012 at a tertiary care center were prospectively enrolled. Stored nodule samples were retrospectively genotyped for the BRAF(V600E) mutation. BRAF(V600E) status, demographics, cytologic and histopathologic findings, and choice of initial surgery were examined.

RESULTS:

A total of 960 patients were enrolled, of which 310 (32%) had an indeterminate nodule. The BRAF(V600E) mutation was identified in 13 patients (4%), 12 of whom had either cytologic atypia or were Bethesda category V. Three percent of Bethesda category III or IV nodules that were malignant harbored the mutation compared with 42% of Bethesda category V malignancies. Nuclear grooves (P = .030), pseudoinclusions (P < .001), and oval nuclei (P = .022) were all more common among BRAF(V600E) mutants. The sensitivities of using BRAF testing alone, cytologic atypia/Bethesda category V classification, or both, were 15%, 73%, and 76%, respectively. Twelve of the 13 BRAF(V600E) mutants had total thyroidectomies initially due to worrisome cytologic features, and therefore the initial management of only one patient would have been altered if BRAF(V600E) testing had been performed preoperatively.

CONCLUSIONS:

Preoperative mutation screening for BRAF(V600E) does not meaningfully improve risk stratification and is unlikely to alter the initial management of patients with indeterminate nodules. Cancer 2013. © 2012 American Cancer Society.
Inhibition of farnesoid X receptor controls esophageal cancer cell growth in vitro and in nude mouse xenografts
Authors: Guan Baoxiang , Li Hao , Yang Zhengduo , Hoque Ashraful , Xu Xiaochun
Published: December 2012

BACKGROUND:

Gastroesophageal reflux is a risk factor for esophageal adenocarcinoma, and bile acid and its farnesoid X receptor (FXR) have been implicated in esophageal tumorigenesis. The authors investigated the role of FXR expression and activity in esophageal cancer initiation and growth.

METHODS:

FXR expression in esophageal adenocarcinoma tissues was assessed by immunohistochemistry. Knockdown of FXR expression in esophageal cancer cells in vitro and in nude mice xenografts was suppressed by FXR small hairpin RNA (shRNA) and guggulsterone (a natural FXR inhibitor). Esophageal cancer cells were treated with bile acids to demonstrate their effects on growth‐promoting genes.

RESULTS:

FXR was expressed in 48 of 59 esophageal adenocarcinoma tissues (81.3%), and this overexpression was associated with higher tumor grade, larger tumor size, and lymph node metastasis; however, was inversely associated with retinoic acid receptor‐β2 (RAR‐β2) expression. Knockdown of FXR expression suppressed tumor cell growth in vitro and in nude mouse xenografts. Guggulsterone reduced the viability of esophageal cancer cells in a time‐dependent and dose‐dependent manner, whereas this effect was diminished after knockdown of FXR expression. Guggulsterone induced apoptosis through activation of caspase‐8, caspase‐9, and caspase‐3 in tumor cells. FXR mediated bile acid‐induced alterations of gene expression, eg, RAR‐β2 and cyclooxygenase‐2 (COX‐2).

CONCLUSIONS:

Inhibition of FXR by FXR shRNA or guggulsterone suppressed tumor cell viability and induced apoptosis in vitro, and it reduced tumor formation and growth in nude mouse xenografts. FXR also mediated bile acid‐induced alterations of cell growth‐related genes in esophageal cancer cells. Cancer 2013. © 2012 American Cancer Society.
Feasibility and safety of sequential research‐related tumor core biopsies in clinical trials
Authors: Lee Jung‐min , Hays John L. , Noonan Anne M. , Squires Jennifer , Minasian Lori , Annunziata Christina , Wood Bradford J. , Yu Minshu , Calvo Katherine R. , Houston Nicole , Azad Nilofer , Kohn Elise C.
Published: December 2012

BACKGROUND:

There has been increasing interest in serial research biopsies in studies of targeted therapies. Definition of patient characteristics and optimal target tissue for safe research tumor biopsy in the era of antiangiogenic and targeted agents is needed.

METHODS:

This institutional review board‐approved, retrospective study included chart and interventional radiology case review from 6 phase 1/2 studies at the National Cancer Institute.

RESULTS:

One hundred forty‐two of 150 protocol patients who were approached gave consent for research biopsies. Patients' median age was 56 years (range, 27‐78 years), their median body mass index was 25.8 kg/m2 (range, 14.4‐46.2 kg/m2), they had an Eastern Cooperative Oncology Group performance status of 0 or 1, and they had normal end‐organ function. Baseline biopsies were collected from 138 of 142 patients (97%), and paired specimens were collected from 96 (70%). Most patients had metastatic gynecologic cancers (85%), and 78% had target disease below the diaphragm with a median size of 2.7 cm (range, 1‐14.5 cm). Protocol therapies included kinase inhibitors (35%), angiogenesis inhibitors (54%), and olaparib/carboplatin (11%); therapy was not interrupted for biopsies. All adverse events were uncomplicated and were observed in 4 patients (liver subcapsular hematoma in 1 patient, vasovagal syncope in 2 patients, and pneumothorax in 1 patient). The complication rate in obese patients was similar to that in nonobese patients (3 of 108 patients vs 1 of 34 patients, respectively). Sixty‐seven patients (48%) were receiving bevacizumab at the time of subsequent biopsies. The complication rate was not different between patients who were and were not receiving bevacizumab (3 of 67 patients vs 1 of 71 patients, respectively). Ninety‐five percent of biopsies yielded useable material.

CONCLUSIONS:

Serial percutaneous core‐needle biopsies can be obtained safely and yield material applicable for multiple translational applications. Obesity and/or concomitant antiangiogenic therapy and depth of disease did not increase the risk or preclude the successful acquisition of useful tissue. Cancer 2013. © 2012 American Cancer Society.
Antioxidant intake and pancreatic cancer risk
Authors: Han Xuesong , Li Jingjing , Brasky Theodore M. , Xun Pengcheng , Stevens June , White Emily , Gammon Marilie D. , He Ka
Published: December 2012

BACKGROUND:

Oxidative stress causes damage to many components of human cells (ie, proteins, lipids, and DNA) and is involved in carcinogenesis. Nutrients with antioxidant properties may protect against oxidative stress. In this study, the authors examined the intake of antioxidants from diet and supplements in relation to pancreatic cancer risk among participants of the Vitamins and Lifestyle (VITAL) Study.

METHODS:

The participants included 77,446 men and women ages 50 to 76 years who were residents of western Washington State and who completed a baseline questionnaire between 2000 and 2002. Participants reported usual diet over the past year and use of supplements over the past 10 years in addition to demographic and lifestyle factors. During a median follow‐up of 7.1 years, 184 participants developed pancreatic adenocarcinoma. Cox proportional hazards models were used to estimate multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 7 antioxidants: β‐carotene, lutein plus zeaxanthin, lycopene, vitamin C, vitamin E, selenium, and zinc.

RESULTS:

An inverse association was observed between dietary selenium and the risk of pancreatic cancer (medium vs low intake: HR, 0.58; 95% CI, 0.35‐0.94; high vs low intake: HR, 0.44; 95% CI, 0.23‐0.85; Ptrend = .01); however, when supplemental and dietary exposures were combined, the association was no longer statistically significant.

CONCLUSIONS:

Dietary selenium intake was inversely associated with the risk of pancreatic cancer, and the observed association was attenuated by selenium supplementation. Cancer 2013. © 2012 American Cancer Society.
Effect of Molecular Crowding on the Temperature–Pressure Stability Diagram of Ribonuclease A
Authors: Zhai Yong , Winter Roland
Published: December 2012

FT‐IR spectroscopic and thermodynamic measurements were designed to explore the effect of a macromolecular crowder, dextran, on the temperature and pressure‐dependent phase diagram of the protein Ribonuclease A (RNase A), and we compare the experimental data with approximate theoretical predictions based on configuration entropy. Exploring the crowding effect on the pressure‐induced unfolding of proteins provides insight in protein stability and folding under cell‐like dense conditions, since pressure is a fundamental thermodynamic variable linked to molecular volume. Moreover, these studies are of relevance for understanding protein stability in deep‐sea organisms, which have to cope with pressures in the kbar range. We found that not only temperature‐induced equilibrium unfolding of RNase A, but also unfolding induced by pressure is markedly prohibited in the crowded dextran solutions, suggesting that crowded environments such as those found intracellularly, will also oppress high‐pressure protein unfolding. The FT‐IR spectroscopic measurements revealed a marked increase in unfolding pressure of 2 kbar in the presence of 30 wt % dextran. Whereas the structural changes upon thermal unfolding of the protein are not significantly influenced in the presence of the crowding agent, through stabilization by dextran the pressure‐unfolded state of the protein retains more ordered secondary structure elements, which seems to be a manifestation of the entropic destabilization of the unfolded state by crowding.
In‐a‐dish: Induced pluripotent stem cells as a novel model for human diseases
Authors: Beltrão‐Braga P. C. B. , Pignatari G. C. , Russo F. B. , Fernandes I. R. , Muotri A. R.
Published: December 2012

Human pluripotent stem cells bring promise in regenerative medicine due to their self‐renewing ability and the potential to become any cell type in the body. Moreover, pluripotent stem cells can produce specialized cell types that are affected in certain diseases, generating a new way to study cellular and molecular mechanisms involved in the disease pathology under the controlled conditions of a scientific laboratory. Thus, induced pluripotent stem cells (iPSC) are already being used to gain insights into the biological mechanisms of several human disorders. Here we review the use of iPSC as a novel tool for disease modeling in the lab. © 2012 International Society for Advancement of Cytometry
Elevation of liver function tests in severe anorexianervosa
Authors: Harris R. Hill , Sasson Gila , Mehler Philip S.
Published: December 2012

Objective:

The purpose of this article is to clarify the finding of liver function test abnormalities in anorexia nervosa (AN).

Method:

Literature review and description of two representative cases of severe liver function test abnormalities from our medical stabilization unit.

Results:

Abnormal elevation of liver function tests can occur during the process of refeeding patients with severe AN. The cause of this elevation is either due to excessive glucose deposition in liver cells or represents liver cell death due to the sequelae of prolonged starvation which characterizes AN before refeeding is adequately in process. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)
Phylogeography of the Indo‐West Pacific maskrays (Dasyatidae, Neotrygon): a complex example of chondrichthyan radiation in the Cenozoic
Authors: Puckridge Melody , Last Peter R. , White William T. , Andreakis Nikos
Published: December 2012

Maskrays of the genus Neotrygon (Dasyatidae) have dispersed widely in the Indo‐West Pacific being represented largely by an assemblage of narrow‐ranging coastal endemics. Phylogenetic reconstruction methods reproduced nearly identical and statistically robust topologies supporting the monophyly of the genus Neotrygon within the family Dasyatidae, the genus Taeniura being consistently basal to Neotrygon, and Dasyatis being polyphyletic to the genera Taeniurops and Pteroplatytrygon. The Neotrygon kuhlii complex, once considered to be an assemblage of color variants of the same biological species, is the most derived and widely dispersed subgroup of the genus. Mitochondrial (COI, 16S) and nuclear (RAG1) phylogenies used in synergy with molecular dating identified paleoclimatic fluctuations responsible for periods of vicariance and dispersal promoting population fragmentation and speciation in Neotrygon. Signatures of population differentiation exist in N. ningalooensis and N. annotata, yet a large‐scale geological event, such as the collision between the Australian and Eurasian Plates, coupled with subsequent sea‐level falls, appears to have separated a once homogeneous population of the ancestral form of N. kuhlii into southern Indian Ocean and northern Pacific taxa some 4–16 million years ago. Repeated climatic oscillations, and the subsequent establishment of land and shallow sea connections within and between Australia and parts of the Indo‐Malay Archipelago, have both promoted speciation and established zones of secondary contact within the Indian and Pacific Ocean basins.
Assembly of a Pentagonal Polyoxomolybdate Building Block, [Mo6O21]6–, into Crystalline MoV Oxides
Authors: Sadakane Masahiro , Endo Keisuke , Kodato Katsunori , Ishikawa Satoshi , Murayama Toru , Ueda Wataru
Published: December 2012

The building‐block assembly of polyoxometalates to form crystalline MoV‐based metal oxides is presented. Mixing of (NH4)6Mo7O24 and VOSO4 in water with a pH value higher than 1.7 produced the ball‐shaped polyoxometalate [Mo72V30O282(H2O)56(SO4)12]36– ({Mo72V30}) with 12 pentagonal [Mo6O21]6– polyoxomolybdate units connected to 30 [V=O]2+ units, which was detected by using UV/Vis, Raman, and IR spectroscopy. Hydrothermal reaction of the precursor containing {Mo72V30} produced crystalline orthorhombic or trigonal MoV oxides. These oxides contain the pentagonal Mo unit in the crystal structure. The results indicate that the pentagonal polyoxomolybdate unit produced in the reaction precursor assembles with other Mo and V ions to form crystalline orthorhombic and trigonal MoV oxides.
N‐Tetradentate SPANamine Derivatives and Their MnII‐Complexes as Catalysts for Epoxidation of Alkenes
Authors: Rich Jordi , Rodríguez Montserrat , Romero Isabel , Fontrodona Xavier , van Leeuwen Piet W. N. M. , Freixa Zoraida , Sala Xavier , Poater Albert , Solà Miquel
Published: December 2012

Five new tetradentate N‐donor ligands with the spirobi(chroman) skeleton (either chiral or racemic) have been synthesized and fully characterized by NMR, ESI‐MS, and optical polarimetry. These ligands have been coordinated to a series of manganese salts, affording a family of new chiral and racemic MnII complexes, which have also been characterized through analytical and spectroscopic techniques. The crystallographic structures of five of them have been obtained by X‐ray diffraction; all show a distorted octahedral geometry with the ligand adopting a cis‐α conformation over the Mn ion. All the complexes have been tested in the catalytic epoxidation of styrene, showing that both conversion and selectivity values increase in the presence of additives in the catalytic media. Experimental results and computational calculations explain the stereospecificity for the cis epoxide in the epoxidation of cis‐β‐methylstyrene mediated by one of the complexes synthesized.
Regio‐ and Diastereoselective Crotylboration of vic‐Tricarbonyl Compounds
Authors: Roßbach Jan , Baumeister Julia , Harms Klaus , Koert Ulrich
Published: December 2012

Crotylboration of vic‐diketoamides and vic‐diketo esters was achieved with high diastereoselectivity and complementary regioselectivity. Whereas (E)‐crotylboration of α,β‐diketoamides resulted in high yields (91–99 %) of β‐crotylated products obtained as a single diastereomer (anti), Lewis acid promoted crotylboration of α,β‐diketo esters yielded the α‐crotylated species with the anti product as main diastereomer.
On the average complexity of sphere decoding in lattice space–time coded multiple‐input multiple‐output channel
Authors: Abediseid Walid
Published: December 2012

The exact average complexity analysis of the basic sphere decoder for general space–time codes applied to multiple‐input multiple‐output (MIMO) wireless channel is known to be difficult. In this work, we shed the light on the computational complexity of sphere decoding for the quasi‐static, lattice space–time (LAST) coded MIMO channel. Specifically, we drive an upper bound of the tail distribution of the decoder's computational complexity. We show that when the computational complexity exceeds a certain limit, this upper bound becomes dominated by the outage probability achieved by LAST coding and sphere decoding schemes. We then calculate the minimum average computational complexity that is required by the decoder to achieve near optimal performance in terms of the system parameters. Our results indicate that there exists a cut‐off rate (multiplexing gain) for which the average complexity remains bounded.Copyright © 2012 John Wiley & Sons, Ltd.
CD44 is required for the migration of transplanted oligodendrocyte progenitor cells to focal inflammatory demyelinating lesions in the spinal cord
Authors: Piao Jing‐Hua , Wang Yanping , Duncan Ian D.
Published: December 2012

Remyelination of chronically demyelinated axons in multiple sclerosis (MS) requires the recruitment of endogenous cells or their replacement by transplanted, exogenous oligodendrocyte progenitor cells (OPCs). We have previously shown that an OPC line, CG4, preferentially migrates after transplantation toward focal areas of inflammatory demyelination and axon loss created by injection of zymosan in the rat spinal cord. Here we show that many transplanted CG4 cells had already migrated into the inflammatory lesion after 1 day. We demonstrate that a large number of CG4 cells that had migrated, expressed the adhesion protein, CD44, and that CD44′s main ligand, hyaluronic acid (HA) was robustly expressed in the inflammatory lesion. In an in vitro migration assay, migration declined significantly following blocking of CD44 expression on CG4 cells. Likewise, migration of CG4 cells toward a zymosan lesion in vivo was inhibited when transplanted cells were exposed to a CD44 blocking antibody prior to transplantation. These findings suggest that CD44 is a key molecule in the migration of OPCs toward the focal inflammatory demyelinated lesion induced by zymosan, and may be an important in OPC repair in MS. © 2012 Wiley Periodicals, Inc.
G protein‐coupled receptor 30 contributes to improved remyelination after cuprizone‐induced demyelination
Authors: Hirahara Yukie , Matsuda Ken Ichi , Yamada Hisao , Saitou Akira , Morisaki Shinsuke , Takanami Keiko , Boggs Joan M. , Kawata Mitsuhiro
Published: December 2012

Estrogen exerts neuroprotective and promyelinating actions. The therapeutic effect has been shown in animal models of multiple sclerosis, in which the myelin sheath is specifically destroyed in the central nervous system. However, it remains unproven whether estrogen is directly involved in remyelination via the myelin producing cells, oligodendrocytes, or which estrogen receptors are involved. In this study, we found that the membrane‐associated estrogen receptor, the G protein‐coupled receptor 30 (GPR30), also known as GPER, was expressed in oligodendrocytes in rat spinal cord and corpus callosum. Moreover, GPR30 was expressed throughout oligodendrocyte differentiation and promyelinating stages in primary oligodendrocyte cultures derived from rat spinal cords and brains. To evaluate the role of signaling via GPR30 in promyelination, a specific agonist for GPR30, G1, was administered to a rat model of demyelination induced by cuprizone treatment. Histological examination of the corpus callosum with oligodendrocyte differentiation stage‐specific markers showed that G1 enhanced oligodendrocyte maturation in corpus callosum of cuprizone‐treated animals. It also enhanced oligodendrocyte ensheathment of dorsal root ganglion (DRG) neurons in co‐culture and myelination in cuprizone‐treated animals. This study is the first evidence that GPR30 signaling promotes remyelination by oligodendrocytes after demyelination. GPR30 ligands may provide a novel therapy for the treatment of multiple sclerosis. © 2012 Wiley Periodicals, Inc.
Acute tryptophan depletion promotes an anterior‐to‐posterior fMRI activation shift during task switching in older adults
Authors: Lamar Melissa , Craig Michael , Daly Eileen M. , Cutter William J. , Tang Christine , Brammer Michael , Rubia Katya , Murphy Declan G.M.
Published: December 2012

Studies have long reported that aging is associated with declines in several functions modulated by the prefrontal cortex, including executive functions like working memory, set shifting, and inhibitory control. The neurochemical basis to this is poorly understood, but may include the serotonergic system. We investigated the modulatory effect of serotonin using acute tryptophan depletion (ATD) during a cognitive switching task involving visual‐spatial set shifting modified for a functional MRI environment. Ten healthy women over 55 years were tested on two separate occasions in this within‐group double‐blind sham‐controlled crossover study to compare behavioral and physiological brain functioning following ATD and following a (“placebo”) sham depletion condition. ATD did not significantly affect task performance. It did modulate brain functional recruitment. During sham depletion women significantly activated the expected task‐relevant brain regions associated with the Switch task including prefrontal and anterior cingulate cortices. In contrast, following ATD participants activated posterior regions of brain more during switch than repeat trials. In addition to the main effects of depletion condition, a comparison of the ATD relative to the sham condition confirmed this anterior‐to‐posterior shift in activation. The posterior (increased) activation clusters significantly and negatively correlated with the reduced prefrontal activation clusters suggesting a compensation mechanism for reduced prefrontal activation during ATD. Thus, serotonin modulates an anterior‐to‐posterior shift of activation during cognitive switching in older adults. Neural adaptation to serotonin challenge during cognitive control may prove useful in determining cognitive vulnerability in older adults with a predisposition for serontonergic down‐regulation (e.g., in vascular or late life depression). Hum Brain Mapp 35:712–722, 2014. © 2012 Wiley Periodicals, Inc.
Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis
Authors: Younes Laurent , Ratnanather J. Tilak , Brown Timothy , Aylward Elizabeth , Nopoulos Peg , Johnson Hans , Magnotta Vincent A. , Paulsen Jane S. , Margolis Russell L. , Albin Roger L. , Miller Michael I. , Ross Christopher A. ,   PREDICT‐HD Investigators and Coordinators of the Huntington Study Group
Published: December 2012

Huntington disease (HD) is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this article, which is based on a dataset extracted from the PREDICT‐HD study, we use statistical shape analysis with deformation markers obtained through “Large Deformation Diffeomorphic Metric Mapping” of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. On the basis of the relation to cortico‐basal ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention. Hum Brain Mapp 35:792–809, 2014. © 2012 Wiley Periodicals, Inc.
Global and focal white matter integrity in breast cancer survivors 20 years after adjuvant chemotherapy
Authors: Koppelmans Vincent , de Groot Marius , de Ruiter Michiel B. , Boogerd Willem , Seynaeve Caroline , Vernooij Meike W. , Niessen Wiro J. , Schagen Sanne B. , Breteler Monique M.B.
Published: December 2012

Objectives

To date, only four small studies have investigated the effects of adjuvant chemotherapy for breast cancer on the microstructure of cerebral white matter with magnetic resonance imaging (MRI). These studies, which were conducted shortly up to 10 years post‐treatment, showed that chemotherapy is associated with focal loss of microstructural white matter integrity. We investigated the long‐term effect of chemotherapy on white matter microstructural integrity by comparing the brains of chemotherapy‐exposed breast cancer survivors to those of a population‐based sample of women without a history of cancer.

Experimental design

Diffusion tensor imaging (DTI) MRI (1.5 T) was performed in 187 CMF (cyclophosphamide, methotrexate, and 5‐flourouracil) chemotherapy‐exposed breast cancer survivors, mean age 64.2 (sd = 6.5) years, who had been diagnosed with cancer on average 21.2 (sd = 4.4) years before, and 374 age‐matched cancer‐free reference subjects from a population‐based cohort study. Outcome measures were whole‐brain microstructural integrity as measured by fractional anisotropy and mean/axial/radial diffusivity and focal white matter integrity, which was analyzed with tract‐based spatial statistics. All analyses were adjusted for age, cardiovascular risk factors, education, and symptoms of depression.

Principal observations

No significant group differences were observed in white matter integrity. However, within the breast cancer survivors, time since treatment was inversely associated with lower global and focal white matter integrity.

Conclusions

This cross‐sectional study suggests that among chemotherapy‐exposed breast cancer survivors white matter microstructural integrity deteriorates with accumulating time since treatment. This warrants further investigation. Hum Brain Mapp 35:889–899, 2014. © 2012 Wiley Periodicals, Inc.
High‐involvement work practices and environmental capabilities: How HIWPS create environmentally based sustainable competitive advantages
Authors: Martínez‐del‐Río Javier , Céspedes‐Lorente José , Carmona‐Moreno Eva
Published: December 2012

We study how high‐involvement work practices (HIWPs) may enhance a firm's economic performance through the development of a proactive environmental strategy (PES). HIWP systems facilitate the implementation of a PES by promoting employees' ability, motivation, and opportunities to behave in ways consistent with environmental management goals. In turn, PESs contribute to the development of strategic competitive advantages and drive superior performance. The results of our empirical analysis of 233 firms broadly confirm our hypotheses and suggest that although the direct effect of HIWPs on performance was not signifi cant in our sample, HIWPs do have a significant indirect effect through a PES as a mediator.
Human resource management and developing proactive environmental strategies: The influence of environmental training and organizational learning
Authors: Vidal‐Salazar María Dolores , Cordón‐Pozo Eulogio , Ferrón‐Vilchez Vera
Published: December 2012

The need to implement advanced approaches to protect the environment is forcing companies to refocus their internal procedures and actions. To match employees' capabilities and the organization itself to these new requirements, the human resource management department can offer some key tools. This article analyzes whether environmental training (ET) and organizational learning (OL) positively influence the development of proactive environmental strategies (PESs) and compares the two processes, which differ in the time, costs, and difficulty required to implement them. Companies in the tourism sector are currently facing a highly dynamic environment where innovativeness is a decisive factor for achieving competitiveness. As such, we analyze whether the presence or absence of innovativeness influences the development of these two mechanisms. Using a sample of 252 tourism companies, we tested these relationships using structural equation modeling. The findings showed that (1) innovativeness is an antecedent of implementing ET and OL in the companies sampled, (2) both mechanisms promote implementing PESs, and (3) ET is equally as effective as OL for this purpose. Managers should take these findings into account when deciding which mechanism to apply when striving to achieve environmental proactivity.
Oral administration of soluble β‐glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor‐bearing mice
Authors: Masuda Yuki , Inoue Hiroko , Ohta Hiroya , Miyake Ayumi , Konishi Morichika , Nanba Hiroaki
Published: December 2012

Maitake D (MD)‐Fraction is a highly purified soluble β‐glucan derived from Grifola frondosa (an oriental edible mushroom). Intraperitoneal (i.p.) injection of MD‐Fraction has been reported to inhibit tumor growth via enhancement of the host immune system. In this study, we demonstrated that oral administration of MD‐Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models. After oral administration, MD‐Fraction was not transferred to the blood in its free form but was captured by antigen‐presenting cells such as macrophages and dendritic cells (DCs) present in the Peyer's patch. The captured MD‐Fraction was then transported to the spleen, thereby inducing the systemic immune response. Our study showed that MD‐Fraction directly induced DC maturation via a C‐type lectin receptor dectin‐1 pathway. The therapeutic response of orally administered MD‐Fraction was associated with (i) induced systemic tumor‐antigen specific T cell response via dectin‐1‐dependent activation of DCs, (ii) increased infiltration of the activated T cells into the tumor and (iii) decreased number of tumor‐caused immunosuppressive cells such as regulatory T cells and myeloid‐derived suppressor cells. Our preclinical study suggests that MD‐Fraction is a useful oral therapeutic agent in the management of patients with cancer.
Therapeutic effect of zinc‐containing calcium phosphate suspension injection in thermal burn‐rats
Authors: Otsuka Makoto , Shikamura Masayuki , Otsuka Kuniko , Sogo Yu , Ito Atsuo
Published: December 2012

The aim of this study was to evaluate the efficacy of suspensions of zinc‐containing tricalcium phosphate (TCP) in the healing of thermal burns in rats. β‐ZnTCP containing 10 mol % zinc, α‐ZnTCP containing 0.9 mol % zinc, and ZnSO4·(H2O)7 (ZnSO4) were used. The injections were prepared to suspend ZnSO4, α‐ZnTCP, and β‐ZnTCP powders in 2 mL of 1% sodium alginate saline solution containing 2 mg of Zn. In vitro Zn release rates were measured in simulated body fluid. The release of Zn from ZnSO4 was very fast, but that from α‐ZnTCP and β‐ZnTCP was slowed by transformation to hydroxyapatite. The suspensions were injected into group C (control), D1 (ZnSO4), D2 (α‐ZnTCP), and D3 (β‐ZnTCP) rats after thermal burns treatment for 3 h. The area under the curve for the plasma Zn for group D1 was the highest, and the order was groups D1 > D2 ≥ D3 ≥ C. The wounded area (Aw) of group D1 had almost the same profile as that of group C, and the Aw at 18 days was about 20%. In contrast, the Aw of group D2 and D3 decreased, and on day 15 was 8% and 37%, respectively. The results indicated that the healing process was shorter in the rats given α‐ZnTCP and β‐ZnTCP than those given ZnSO4 or the control. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
The innovative application of a novel bone adhesive for facial fracture osteosynthesis—in vitro and in vivo results
Authors: Smeets Ralf , Endres Kira , Stockbrink Gereon , Hanken Henning , Hermanns‐Sachweh Benita , Marx Rudolf , Heiland Max , Blessmann Marco , Wolff Klaus‐Dietrich , Kolk Andreas
Published: December 2012

This study evaluates a novel adhesive fixation technique to affix cortical bone fragments to osteosynthesis plates using common PMMA cement. This technique utilizes a new amphiphilic bone bonding agent adhering with both hydrophilic bone and hydrophobic PMMA cement. After in vitro biomechanical testing of the bonding strength with explanted bovine and rabbit calvarian bone samples, osteosynthesis plates with screw holes of 1.3 and 1.5 mm were placed on the cranial bone of New Zealand white rabbits and the bond strength of these plates was determined through tension tests. In vitro bond strengths of 19.8–26.5 MPa were obtained. Control samples, prepared without a bone bonding agent, exhibited bone bonding strengths <0.2 MPa. In vivo respective bond strengths at the cranium of the white rabbits were 2.5–4.1 MPa 2 weeks post surgery and 1.9–2.5 MPa 12 weeks after implantation. This new innovative fixation method can be envisioned for cases in which conventional fixation techniques of screws and plates are insufficient or not possible due to the bone or trauma conditions. The observed bonding strengths support implementing this technique in nonload bearing regions, such as the central midface or frontal sinus, facilitating immobilization until bone reunion is complete. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Mechanical attachment of soft tissue to dental and maxillofacial implants with mesh structures: An experiment in percutaneous model
Authors: Asoda Seiji , Arita Takayuki , Takakuda Kazuo
Published: December 2012

Soft tissue attachment is a major concern for the improved design of dental and maxillofacial implants. This study evaluated the efficacy of mesh structures for soft tissue attachment in a rat percutaneous model. Four kinds of implant specimens were prepared — TI implants made of titanium cylinders, HA implants of hydroxyapatite‐coated titanium, TI‐Mesh implants with a titanium mesh covering a groove machined around a titanium cylinder, and similar HA‐Mesh implants with a hydroxyapatite‐coated mesh. These specimens were implanted percutaneously into the skin tissue of rats. The detachments of the implants were examined during the experimental period of 4 weeks. Survived implants were subjected to mechanical tests for the attachment strength and histological examinations. TI and HA implants demonstrated 0% of survival rates, while TI‐Mesh and HA‐Mesh showed significantly higher rates of 93.3% and 100% respectively. The attachment strengths were 159 ± 47 kPa in the TI‐Mesh and 135 ± 16 kPa in the HA‐Mesh. Histological observations revealed that collagen fibers originating from surrounding subcutaneous tissues were anchored to the mesh structures of the TI‐ and HA‐Mesh implants. The results demonstrated the efficacy of the mesh structures for the attachment of soft connective tissues to implants. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.