bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Synthesis of Bridged Bicyclic β‐Trifluoroacetoxy β‐ Trifluoromethyl α‐Amino Acid Derivatives by an Original Dakin‐ West/Diels‐Alder Tandem Sequence.
Authors: CUFOS T. , DIAZ P. , STELLA L.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Convenient De Novo Synthesis of Functionalized 2,4,6,8‐ Tetraoxaadamantanes.
Authors: HEILMAYER W. , DALVI T. S. , KAPPE C. O. , WENTRUP C. , GRUBER K. , STERK H. , KOLLENZ G.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Regioselective Synthesis of Substituted and Fused Pyrazolo(1,5‐a) pyrimidines as Leishmanicides.
Authors: RAM V. J. , NATH M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis of 1‐(2‐(4‐Phenylpiperazinyl‐1)ethyl)imidazolidine Derivatives and Their Pharmacological Activity.
Authors: KULINSKI T. , TKACZYNSKI T.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Simple and Condensed β‐Lactams. Part 19. Synthesis of Some New 7‐ Acylamino‐2‐iso‐oxacephem‐4‐carboxylic Acids.
Authors: TOMBOR Z. , GREFF Z. , NYITRAI J. , KAJTAR‐PEREDY M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Structural Studies of a New Class of Heterocyclic Compounds: 1,2,4‐Pyridothiadiazine 1,1‐Dioxides, Pyridyl Analogues of 1,2,4‐Benzothiadiazine 1,1‐Dioxides.
Authors: DE TULLIO P. , PIROTTE B. , DUPONT L. , MASEREEL B. , LAECKMANN D. , PODONA T. , DIOUF O. , LEBRUN P. , DELARGE J.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Crystal Structure of a New Large Cryptand Encapsulating a Benzene Molecule.
Authors: JANSSEN R. J. A. , LINDOY L. F. , MATTHEWS O. A. , MEEHAN G. V. , SOBOLEV A. N. , WHITE A. H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: An Efficient Approach to the Synthesis of 1,1‐Diphenyl‐1‐ silacycloheptan‐4‐one.
Authors: DAMOUR D. , RENAUDON A. , MIGNANI S.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Facile Access to the ABC Ring System of the Taxane Diterpenes via Anionic Oxy‐Cope Rearrangements.
Authors: MARTIN S. F. , ASSERCQ J.‐M. , AUSTIN R. E. , DANTANARAYANA A. P. , FISHPAUGH J. R. , GLUCHOWSKI C. , GUINN D. E. , HARTMANN M. , TANAKA T. , WAGNER R. , WHITE J. B.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: A Short Synthesis of Hinesol (I) and Agarospirol (II) via Photochemical Construction of Vetispirane Framework Based on the retro‐ Benzilic Acid Rearrangement.
Authors: HATSUI T. , WANG J.‐J. , IKEDA S. , TAKESHITA H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Total Synthesis of cis‐Clerodane Diterpenoids: (‐)‐Agelasine A and (+)‐ (3R,4S,5R,8S,9R,10S)‐3,4‐Epoxyclerod‐13‐en‐15,16‐olide.
Authors: PIERS E. , BREAU M. L. , HAN Y. , PLOURDE G. L. , YEH W.‐L.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Stereospecific Cyclization to Form C‐Furanosides.
Authors: YANG B.‐H. , JIANG J.‐Q. , MA K. , WU H.‐M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Ozonation of Thionucleosides. A New Chemical Transformation of 4‐ Thiouracil and 6‐Thioguanine Nucleosides to Cytosine and Adenosine Counterparts.
Authors: SALADINO R. , CRESTINI C. , OCCHIONERO F. , NICOLETTI R.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis of 3′‐Amino‐3′‐deoxyadenosine from Levoglucosenone.
Authors: KUNO H. , NIIHATA S. , EBATA T. , MATSUSHITA H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthetic Studies Related to the Esperamicin/Calicheamicin Aglycone: Efficient Construction of a Homochiral Oxabicyclo (7:3:1) Analogue from D‐Xylose.
Authors: DANCY I. , SKRYDSTRUP T. , CREVISY C. , BEAU J.‐M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Toughening and Strengthening of Alumina with Silver Inclusions.
Authors: CHOU W. B. , TUAN W. H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Pattern Formation on Catalytic Surfaces
Authors: EISWIRTH M. , ERTL G.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Cycloheptatriene and ‐enyl Complexes of the Early Transition‐Metals
Authors: GREEN M. L. H. , NG D. K. P.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Emerging Applications of Asymmetric Dihydroxylation Chemistry
Authors: JAYAMMA Y. , NANDANAN E. , LOHRAY B. B.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Thermolysis Reactions of Si‐Functionalized 2‐ Silaazetidines
Authors: WEINGARTNER A. , ZICHE W. , AUNER N.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Unusual Coordination in Phosphorus Silicon Compounds
Authors: BENDER H. R. G. , KLEIN E. , NIECKE E. , NIEGER M. , RANAIVONJATOVO H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Ex vivo analysis of SIV‐infected cells by flow cytometry
Authors: Reynolds Matthew R. , Piaskowski Shari M. , Weisgrau Kimberly L , Weiler Andrea M. , Friedrich Thomas C. , Rakasz Eva G.
Published: August 2010

Deciphering the complex interactions between human and simian immunodeficiency viruses (HIV/SIV) and their host cells is crucial to the development of improved therapies and vaccines. Investigating these relationships has been complicated by the inability to directly analyze infected cells among freshly isolated peripheral blood lymphocytes. Here, we describe a method to detect cells productively infected with SIVmac239 ex vivo from the blood or lymph nodes by flow cytometry. Using this method, we show a close correlation between the frequency of productively infected cells in both sample type and the plasma viral load. We define that the minimum threshold for detecting productively infected cells in lymph nodes by flow cytometry requires a plasma virus concentration of ∼2.5 × 104 vRNA copy Equivalents (Eq)/ml. Conversely, an approximately 2 logs higher plasma viral load is needed to detect productively infected cells in the peripheral blood. This novel protocol provides a direct analytical tool to assess interactions between SIV and host cells, which is of key importance to investigators in AIDS research. © 2010 International Society for Advancement of Cytometry.
Synthesis and Electrical Capacitance of Carbon Nanoplates
Authors: Mei Tao , Li Ting , Bi Huiyun , Wang Liangbiao , Zhu Yongchun , Qian Yitai
Published: August 2010

Carbon nanoplates with diameters and thicknesses of up to approximately 1.2 μm and 18 nm, respectively, were prepared by a reaction using CaC2, ferrocene, and NH4HCO3 as starting materials at 600 °C for 10 h. These carbon nanoplates form aggregates that have a specific surface area of up to 831 m2 g–1 and a specific capacitance of up to 184 F g–1 at a scanning rate of 10 mV s–1 in a 3 mol L–1 H2SO4 solution. Without using NH4HCO3, hexagonal carbon nanoplates with an average edge length of 500 nm and thickness of approximately 22 nm were obtained with a specific capacitance of up to 42 F g–1. If NaN3 or NaHCO3 was used instead of NH4HCO3, carbon nanoplates with a curved surface or irregular circular carbon nanoplates were obtained with specific capacitances of 87 or 36 F g–1, respectively.
Inflation bulb‐driven microfluidic reactor for infrared‐assisted proteolysis
Authors: Liu Ting , Bao Huimin , Chen Gang
Published: August 2010

In this report, an inflation bulb‐driven microfluidic reactor was developed for IR‐accelerated proteolysis. This novel proteolysis system mainly consisted of an inflation bulb‐driving system, a simple cross‐PMMA microchip, and a temperature‐controllable IR radiation system. The gas pressure generated from an inflation bulb was employed to drive protein and trypsin solutions to flow into the main channel of the microchip via two capillaries and the injection channel. When the two solutions were mixed in the channel, the protein was rapidly digested by trypsin under IR radiations. The peptides in the digests accumulated in the product reservoir of the microchip were subsequently identified by MS. The feasibility and performance of this unique system were demonstrated by digesting hemoglobin and lysozyme. The results indicated that IR radiation could significantly enhance the on‐chip proteolysis and the digestion time was substantially reduced to 5 min. The present proteolysis setup is simple and efficient and will find wide applications in high‐throughput protein digestion.
Total analysis of endocrine disruptors in a microchip with gold nanoparticles
Authors: Noh Hui‐Bog , Lee Kyung‐Sun , Lim Bo Seul , Kim So‐Jin , Shim Yoon‐Bo
Published: August 2010

The development of a simple, sensitive, and direct method for the total analysis of certain endocrine disruptors was performed by integrating preconcentration steps to a separation step on a microchip through the modification of the field‐amplified sample stacking and field‐amplified sample injection steps. To improve the preconcentration and separation performances, the preconcentration and separation buffers were modified with citrate‐stabilized gold nanoparticles (AuNPs). For the detection of the separated samples, cellulose‐dsDNA/AuNPs‐modified carbon paste electrodes were used at the channel end. The experimental parameters affecting the analytical performances, such as the buffer concentration, water plug length, SDS concentration in the separation buffer, AuNPs concentration, preconcentration time, detection potential and electrode to channel distance, were examined. The detection limits of the test compounds were between 7.1 and 11.1 fM and that for 4‐pentylphenol was 7.1 (±1.1) fM. Dynamic ranges were in the range from 0.15 to 600.0 pM. The experiments with real samples were performed to evaluate the reliability of the proposed method.
Regression approaches to derive generic and fish group-specific probability density functions of bioconcentration factors for metals
Authors: Tanaka Taku , Ciffroy Philippe , Stenberg Kristofer , Capri Ettore
Published: August 2010

In the framework of environmental multimedia modeling studies dedicated to environmental and health risk assessments of chemicals, the bioconcentration factor (BCF) is a parameter commonly used, especially for fish. As for neutral lipophilic substances, it is assumed that BCF is independent of exposure levels of the substances. However, for metals some studies found the inverse relationship between BCF values and aquatic exposure concentrations for various aquatic species and metals, and also high variability in BCF data. To deal with the factors determining BCF for metals, we conducted regression analyses to evaluate the inverse relationships and introduce the concept of probability density function (PDF) for Cd, Cu, Zn, Pb, and As. In the present study, for building the regression model and derive the PDF of fish BCF, two statistical approaches are applied: ordinary regression analysis to estimate a regression model that does not consider the variation in data across different fish family groups; and hierarchical Bayesian regression analysis to estimate fish group-specific regression models. The results show that the BCF ranges and PDFs estimated for metals by both statistical approaches have less uncertainty than the variation of collected BCF data (the uncertainty is reduced by 9%–61%), and thus such PDFs proved to be useful to obtain accurate model predictions for environmental and health risk assessment concerning metals. Environ. Toxicol. Chem. 2010;29:2417–2425. © 2010 SETAC
Relationship of PCDD/F concentrations in duck-egg farmers and consumption of ranched duck eggs in central Taiwan
Authors: Chen Hsiu-Ling , Huang Po-Chin , Lee Ching-Chang
Published: August 2010

The 2004 food market-basket survey in Taiwan found high levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in duck eggs. A subsequent survey in Chang-Hua County, central Taiwan, found nine duck farms for egg production and duck eggs that were highly contaminated by PCDD/Fs in the secondary sampling and analysis during the years 2004 to 2005. Duck-egg farmers eat duck eggs rather than chicken eggs, and the aim of the current study was to evaluate how eating contaminated duck eggs affected serum PCDD/F accumulation and PCDD/F profiles in family members of duck-egg farmers. Forty-two family members of duck-egg farmers and 88 residents living nearby (control group) were recruited. Serum PCDD/F levels were significantly higher in duck-egg farmers than in the control group (28.1 vs 18.6 pg World Health Organization toxic equivalency [TEQ]/g lipid, WHO-TEQ). Significant differences in PCDD/F levels were found for most congeners, especially for 2,3,4,7,8-penta–chlorinated dibenzofurans. Elevated serum PCDD/F levels were positively associated with an increase in monthly duck-egg consumption after adjustments for fish consumption. The current result contradicted results of our previous study, which showed a positive association between fish intake and serum PCDD/F levels. The matter of cultivation in the contaminant area in Chang-Hua County should be considered more seriously. Environ. Toxicol. Chem. 2010;29:2402–2408. © 2010 SETAC
The effect of natural dissolved organic carbon on the acute toxicity of copper to larval freshwater mussels (glochidia)
Authors: Gillis Patricia L. , McGeer James C. , Mackie Gerald L. , Wilkie Michael P. , Ackerman Josef D.
Published: August 2010

The present study examined the effect of dissolved organic carbon (DOC), both added and inherent, on Cu toxicity in glochidia, the larvae of freshwater mussels. Using incremental additions of natural DOC concentrate and reconstituted water, a series of acute copper toxicity tests were conducted. An increase in DOC from 0.7 to 4.4 mg C/L resulted in a fourfold increase (36–150 µg Cu/L) in the 24-h median effective concentration (EC50) and a significant linear relationship (r2 = 0.98, p = 0.0008) between the DOC concentration and the Cu EC50 of Lampsilis siliquoidea glochidia. The ameliorating effect of added DOC on Cu toxicity was confirmed using a second mussel species, the endangered (in Canada) Lampsilis fasciola. The effect of inherent (i.e., not added) DOC on Cu toxicity was also assessed in eight natural waters (DOC 5–15 mg C/L). These experiments revealed a significant relationship between the EC50 and the concentration of inherent DOC (r2 = 0.79, p = 0.0031) with EC50s ranging from 27 to 111 µg Cu/L. These laboratory tests have demonstrated that DOC provides glochidia with significant protection from acute Cu toxicity. The potential risk that Cu poses to mussel populations was assessed by comparing Cu and DOC concentrations from significant mussel habitats in Ontario to the EC50s. Although overall mean Cu concentration in the mussel's habitat was well below the acutely toxic level given the concentration of DOC, episodic Cu releases in low DOC waters may be a concern for the recovery of endangered freshwater mussels. The results are examined in the context of current Cu water quality regulations including the U.S. Environmental Protection Agency's (U.S. EPA) biotic ligand model. Environ. Toxicol. Chem. 2010;29:2519–2528. © 2010 SETAC
Improved Glycemic Control with Colesevelam Treatment in Patients with Type 2 Diabetes Is Not Directly Associated with Changes in Bile Acid Metabolism
Authors: Brufau Gemma , Stellaard Frans , Prado Kris , Bloks Vincent W. , Jonkers Elles , Boverhof Renze , Kuipers Folkert , Murphy Elizabeth J.
Published: August 2010

Bile acids (BAs) are essential for fat absorption and appear to modulate glucose and energy metabolism. Colesevelam, a BA sequestrant, improves glycemic control in type 2 diabetes mellitus (T2DM). We aimed to characterize the alterations in BA metabolism associated with T2DM and colesevelam treatment and to establish whether metabolic consequences of T2DM and colesevelam are related to changes in BA metabolism. Male subjects with T2DM (n = 16) and controls (n = 12) were matched for age and body mass index. BA pool sizes and synthesis/input rates were determined before and after 2 and 8 weeks of colesevelam treatment. T2DM subjects had higher cholic acid (CA) synthesis rate, higher deoxycholic acid (DCA) input rate, and enlarged DCA pool size. Colesevelam resulted in a preferential increase in CA synthesis in both groups. CA pool size was increased whereas chenodeoxycholic acid and DCA pool sizes were decreased upon treatment. Fasting and postprandial fibroblast growth factor 19 (FGF19) levels did not differ between controls and diabetics, but were decreased by treatment in both groups. Colesevelam treatment reduced hemoglobin A1C by 0.7% (

P

< 0.01) in diabetics. Yet, no relationships between BA kinetic parameters and changes in glucose metabolism were found in T2DM or with colesevelam treatment.

Conclusion:

Our results reveal significant changes in BA metabolism in T2DM, particularly affecting CA and DCA. Colesevelam treatment reduced FGF19 signaling associated with increased BA synthesis, particularly of CA, and resulted in a more hydrophilic BA pool without altering total BA pool size. However, these changes could not be related to the improved glycemic control in T2DM. (Hepatology 2010;)
Increased Natural Killer Cell Cytotoxicity and NKp30 Expression Protects Against Hepatitis C Virus Infection in High-Risk Individuals and Inhibits Replication In Vitro
Authors: Golden-Mason Lucy , Cox Andrea L. , Randall Jessica A. , Cheng Linling , Rosen Hugo R.
Published: August 2010

CD56pos natural killer (NK)/natural T (NT) cells are important innate effectors providing the first line of defense against viral infection. Enhanced NK activity has been shown to protect from human immunodeficiency virus-1 infection. However, the role played by these innate effectors in protection against or development of hepatitis C virus (HCV) infection is unknown. We characterized CD56pos populations in 11 injection drug users (IDUs) who remained uninfected despite being repeatedly exposed to HCV. NK profiles in exposed but uninfected (EU) individuals were compared with preinfection samples (median 90 days prior to HCV seroconversion) collected from 14 IDUs who were exposed and subsequently became infected (EI) and unexposed normal control subjects (n = 8). Flow cytometric analysis of CD56pos populations demonstrated that EUs had a higher proportion of CD56low mature (

P

= 0.0011) NK cells compared with EI subjects. Bead-isolated NKs (>90% purity) from EUs had significantly higher interleukin-2 (IL-2)–induced cytolytic activity against the NK-sensitive cell line K562 at an effector-to-target ratio of 10:1 (

P

< 0.0001). NKp30, a natural cytotoxicity receptor involved in NK activation, is highest on NK/NT cells in EUs relative to infected subjects. Using the JFH-1 infection system, we demonstrated that NKp30high cells in the absence of exogenous stimulation significantly reduce infection of hepatocytes.

Conclusion:

CD56pos populations in EUs are enriched for effector NKs displaying enhanced IL-2–induced cytolytic activity and higher levels of the natural cytotoxicity receptor NKp30-activating receptor. In addition, NKp30high cells are more effective in preventing infection of Huh-7.5 cells than their NKp30low/neg counterparts. These data support the hypothesis that NK cells contribute to anti-HCV defense

in vivo

in the earliest stages of infection, providing innate protection from HCV acquisition. (Hepatology 2010)
Antiviral Activity of Narlaprevir Combined with Ritonavir and Pegylated Interferon in Chronic Hepatitis C Patients
Authors: de Bruijne Joep , Bergmann Jilling F. , Reesink Henk W. , Weegink Christine J. , Molenkamp Richard , Schinkel Janke , Tong Xiao , Li Jing , Treitel Michelle A. , Hughes Eric A. , van Lier Jan Jaap , van Vliet Andre A. , Janssen Harry L. A. , de Knegt Robert J.
Published: August 2010

Narlaprevir (SCH 900518) is a potent inhibitor of the hepatitis C virus (HCV) nonstructural protein 3 serine protease that is primarily metabolized by the cytochrome P450-3A4 system. In order to explore the use of ritonavir-based pharmacokinetic enhancement of an HCV protease inhibitor, this study investigated the safety, tolerability, pharmacokinetics, and antiviral activity of narlaprevir (with or without ritonavir) administered as monotherapy and as combination therapy with pegylated interferon-α-2b (PEG-IFN-α-2b) to HCV genotype 1–infected patients. This was a randomized, placebo-controlled, two-period, blinded study in 40 HCV genotype 1–infected patients (naïve and treatment-experienced). In period 1, narlaprevir was administered for 7 days as 800 mg three times daily without ritonavir or 400 mg twice daily with 200 mg ritonavir twice daily. In period 2, after a 4-week washout, the same dose and regimen of narlaprevir was administered in combination with PEG-IFN-α-2b for 14 days. Upon completion of period 2, all patients initiated PEG-IFN-α-2b and ribavirin treatment. A rapid and persistent decline in plasma HCV-RNA was observed in both treatment-experienced and treatment-naïve patients during period 1, with a mean viral load decline of at least 4 log10 in all treatment groups. A high percentage of both treatment-experienced (50%) and treatment-naïve (≥60%) patients had undetectable HCV-RNA (<25 IU/mL) after period 2. Standard of care resulted in sustained virological response (SVR) rates of 38% and 81% in treatment-experienced and treatment-naïve patients, respectively. Narlaprevir (with or without ritonavir) alone or in combination with PEG-IFN-α-2b was safe and well tolerated.

Conclusion:

Narlaprevir administration resulted in a robust HCV-RNA decline and high SVR rates when followed by standard of care in both treatment-experienced and treatment-naïve HCV genotype 1–infected patients. (Hepatology 2010
Coffee Reduces Liver Damage in a Rat Model of Steatohepatitis: The Underlying Mechanisms and the Role of Polyphenols and Melanoidins
Authors: Vitaglione Paola , Morisco Filomena , Mazzone Giovanna , Amoruso Daniela Caterina , Ribecco Maria Teresa , Romano Antonietta , Fogliano Vincenzo , Caporaso Nicola , D'Argenio Giuseppe
Published: August 2010

Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70-kg person) were added for 8 weeks to the drinking water of rats who were being fed a high-fat, high-calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two-fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF-α), tissue transglutaminase, and transforming growth factor β and increased expression of adiponectin receptor and peroxisome proliferator-activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF-α and interferon-γ and increased anti-inflammatory interleukin-4 and interleukin-10.

Conclusion:

Our data demonstrate that coffee consumption protects the liver from damage caused by a high-fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid β-oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation. (Hepatology 2010;52:1652-1661)
MicroRNA-125b Suppressesed Human Liver Cancer Cell Proliferation and Metastasis by Directly Targeting Oncogene LIN28B
Authors: Liang Linhui , Wong Chun-Ming , Ying Qiao , Fan Dorothy Ngo-Yin , Huang Shenglin , Ding Jie , Yao Jian , Yan Mingxia , Li Jinjun , Yao Ming , Ng Irene Oi-Lin , He Xianghuo
Published: August 2010

MicroRNAs (miRNAs) are small, noncoding RNAs that can act as oncogenes or tumor suppressors in human cancer. Our previous study showed that miR-125b was a prognostic indicator for patients with hepatocellular carcinoma (HCC), but its functions and exact mechanisms in hepatic carcinogenesis are still unknown. Here we demonstrate that miR-125b suppressed HCC cell growth

in vitro

and

in vivo

. Moreover, miR-125b increased p21Cip1/Waf1 expression and arrested cell cycle at G1 to S transition. In addition, miR-125b inhibited HCC cell migration and invasion. Further studies revealed that

LIN28B

was a downstream target of miR-125b in HCC cells as miR-125b bound directly to the 3′ untranslated region of

LIN28B

, thus reducing both the messenger RNA and protein levels of

LIN28B

. Silencing of

LIN28B

recapitulated the effects of miR-125b overexpression, whereas enforced expression of

LIN28B

reversed the suppressive effects of miR-125b.

Conclusion:

These findings indicate that miR-125b exerts tumor-suppressive effects in hepatic carcinogenesis through the suppression of oncogene

LIN28B

expression and suggest a therapeutic application of miR-125b in HCC. (Hepatology 2010)
Characterization of aneurysmal aortas by biochemical, thermal, and dielectric techniques
Authors: Samouillan Valerie , Dandurand Jany , Lacabanne Colette , Stella Andrea , Gargiulo Mauro , Degani Annamaria , Gandaglia Alessandro , Spina Michel
Published: August 2010

Abdominal aortic aneurysms (AAA) are characterized by structural alterations of the aortic wall resulting from the degradation of elastic fibres and an increase of collagen/elastin ratio. In this study we investigated the chain dynamics of AAA tissues by two techniques generally used for the characterization of polymers, Differential scanning calorimetry (DSC) and thermally stimulated currents (TSC), and we correlated the obtained data with biochemical analyses. The thermal denaturation of collagen observed by DSC allowed us to evaluate the thermal stability of the triple helix domain: notable modifications were evidenced between collagen from control tissue and collagen from AAA, particularly concerning the thermal denaturation. The dielectric analysis of pathologic aortic walls by TSC revealed a relevant change of collagen mobility in AAA, with the occurrence of a specific mode of relaxation between −60 and −40°C. Biochemical, thermal, and dielectric results are compatible with increase of new collagen deposition and/or impairment of the collagen phase stability in the extracellular matrix of AAAs. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Pluronic/chitosan hydrogels containing epidermal growth factor with wound‐adhesive and photo‐crosslinkable properties
Authors: Choi Ji Suk , Yoo Hyuk Sang
Published: August 2010

Wound‐adhesive and thermo‐responsive hydrogels were prepared in an aim to develop a wound‐care device for diabetic ulcers. A mixture of glycidyl methacrylated chitooligosaccharide (COS), di‐acrylated Pluronic, and a recombinant human epidermal growth factor (rhEGF) formed a physical hydrogel. Photo‐irradiation was subsequently applied to chemically crosslink the hydrogel. Release profiles of encapsulated rhEGF from the hydrogel showed that release rates were dependent on degradation rates of hydrogels. Human primary keratinocytes were cultivated with the released fraction from the hydrogel to measure effects of released rhEGF on in vitro differentiation of keratinocytes. Muco‐adhesive property of the hydrogel was investigated in animal skins and significant amounts of quantum dot‐labeled rhEGF were retained at wound sites along with chitosan. The hydrogel was administered to dorsal burn wounds in wound healing impaired animals and photo‐irradiated. COS and rhEGF in the hydrogels significantly enhanced epidermal differentiation during the wound healing process. Thus, the rhEGF‐encapsulated hydrogel was expected to be a potential wound care product by increasing local concentration of rhEGF at wound sites with maintaining keratinocytic differentiation. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Antibacterial coatings of fluoridated hydroxyapatite for percutaneous implants
Authors: Ge Xiang , Leng Yang , Bao Chongyun , Xu Sherry Li , Wang Renke , Ren Fuzeng
Published: August 2010

Percutaneous orthopedic and dental implants require not only good adhesion with bone but also the ability to attach and form seals with connective tissues and the skin. To solve the skin‐seal problem of such implants, an electrochemical deposition method was used to modify the surfaces of metallic implants to improve their antibacterial ability and skin seals around them. A dense and uniform fluoridated calcium phosphate coating with a thickness of about 200 nm was deposited on an acid‐etched pure titanium substrate by controlling the current density and reaction duration of the electrochemical process. The as‐deposited amorphous fluoridated calcium phosphate transformed to fluoridated hydroxyapatite (FHA) after heat treatment at 600°C in a water vapor environment for 3 h. Both single crystal diffraction patterns and high‐resolution transmission electron microscope (HRTEM) images confirmed the phase of the fluoridated calcium phosphate after the heat treatment. The antibacterial activities of FHA coatings were tested against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Porphyromonas gingivalis (P. gingivalis) with the film attachment method. The antibacterial activity of FHA coating is much higher than that of pure hydroxyapatite (HA) coating and acid‐etched pure titanium surface. The promising features of FHA coating make it suitable for orthopedic and dental applications. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Paracrine factors from fibroblast aggregates in a fibrin‐matrix carrier enhance keratinocyte viability and migration
Authors: Peura Matti , Siltanen Antti , Saarinen Ira , Soots Anu , Bizik Jozef , Vuola Jyrki , Harjula Ari , Kankuri Esko
Published: August 2010

Efficient re‐epithelialization of skin lesions is dependent on paracrine support from connective tissue fibroblasts. In deep skin defects, the supporting growth factor incentive is lacking. Current methods of keratinocyte transplantation with compromised attachment, spread, and cell proliferation warrant improvement and refinement. We describe here how human keratinocytes can be stimulated by matrix‐embedded factors from a novel process of fibroblast activation: nemosis. Interestingly, the unique set of mediators released in this process also plays a key role in normal wound healing. To develop a system for targeted delivery of nemosis‐derived paracrine effectors, herein designated as Finectra, we combined them with fibrin to establish a controlled‐release gel. Keratinocytes seeded to cover this active matrix showed better adherence, outgrowth, and viability than did cells on control matrix. The matrix incorporating Finectra supported viability of both primary keratinocytes and green fluorescent protein (GFP)‐labeled HaCaT cells, as evaluated by MTT assay and persistence of GFP‐fluorescence. The fibrin‐Finectra matrix promoted migration of keratinocytes to cover a larger area on the matrix, suggesting better wound coverage on transplantation. An inhibitor of EGFR/c‐Met receptor tyrosine kinases abolished keratinocyte responses to fibrin‐Finectra matrix. This matrix can thus deliver biologically relevant synergistic stimuli to keratinocytes and hasten re‐epithelialization. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor‐1
Authors: Khanna Omaditya , Moya Monica L. , Opara Emmanuel C. , Brey Eric M.
Published: August 2010

Alginate microcapsules coated with a permselective poly‐L‐ornithine (PLO) membrane have been investigated for the encapsulation and transplantation of islets as a treatment for type 1 diabetes. The therapeutic potential of this approach could be improved through local stimulation of microvascular networks to meet mass transport demands of the encapsulated cells. Fibroblast growth factor‐1 (FGF‐1) is a potent angiogenic factor with optimal effect occurring when it is delivered in a sustained manner. In this article, a technique is described for the generation of multilayered alginate microcapsules with an outer alginate layer that can be used for the delivery of FGF‐1. The influence of alginate concentration and composition (high mannuronic acid (M) or guluronic acid (G) content) on outer layer size and stability, protein encapsulation efficiency, and release kinetics was investigated. The technique results in a stable outer layer of alginate with a mean thickness between 113 and 164 μm, increasing with alginate concentration and G‐content. The outer layer was able to encapsulate and release FGF‐1 for up to 30 days, with 1.25% of high G alginate displaying the most sustained release. The released FGF‐1 retained its biologic activity in the presence of heparin, and the addition of the outer layer did not alter the permselectivity of the PLO coat. This technique could be used to generate encapsulation systems that deliver proteins to stimulate local neovascularization around encapsulated islets. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
In vivo evaluation of MMP sensitive high‐molecular weight HA‐based hydrogels for bone tissue engineering
Authors: Kim Jungju , Kim In Sook , Cho Tae Hyung , Kim Ho Chul , Yoon So Jeong , Choi Jaesoon , Park Yongdoo , Sun Kyung , Hwang Soon Jung
Published: August 2010

Hyaluronic acid (170 kDa)‐based hydrogel was synthesized using acrylated hyaluronic acid (HA) and matrix metalloproteinase (MMP) sensitive HA‐based hydrogels were then prepared by conjugation with two different peptides: cell adhesion peptides containing integrin‐binding domains (Arg‐Gly‐Asp: RGD) and a cross‐linker with MMP degradable peptides to mimic the remodeling characteristics of natural extracellular matrices by cell‐derived MMPs. Mechanical properties of these hydrogels were evaluated with different weight percentages (2.5 and 3.5 wt %) by measuring elastic modulus, viscous modulus, and swelling ratio. Human mesenchymal stem cells (hMSCs) were then cultured in MMP‐sensitive or insensitive HA‐based hydrogels and/or immobilized cell adhesive RGD peptides in vitro. Actin staining and image analysis proved that cells cultured in the MMP‐sensitive hydrogel with RGD peptides showed extensive cell spreading and sprouting. Gene expression analysis showed that bone specific genes such as alkaline phosphatase, osteocalcin, and osteopontin increased in MMP‐sensitive hydrogels as biomolecules such as BMPs and cells were added in the gels. For in vivo calvarial defect regeneration, five different samples (MMP insensitive hydrogel, MMP sensitive hydrogel, MMP sensitive hydrogel with BMP‐2, MMP sensitive hydrogel with hMSC, and MMP sensitive hydrogel with BMP‐2 and hMSC) were prepared. After 4 weeks of implantation, the Masson‐Trichrome staining and micro computed tomography scan results demonstrated that the MMP sensitive hydrogels with BMP‐2 and hMSCs have the highest mature bone formation. The MMP sensitive HA‐based hydrogel could become useful scaffolds in bone tissue engineering with improvements on tissue remodeling rates and regeneration activity. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Rough surface topography enhances the activation of Wnt/β‐catenin signaling in mesenchymal cells
Authors: Galli Carlo , Passeri Giovanni , Ravanetti Francesca , Elezi Erida , Pedrazzoni Mario , Macaluso Guido Maria
Published: August 2010

It is known that the roughness of titanium surfaces affects cell proliferation and differentiation. However, the mechanisms mediating the cellular responses to surface topography are only partially understood. The present study investigated whether Wnt canonical signaling, an important pathway in determining cell fate, is modulated by surface roughness. This study analyzed the behavior of the murine C2C12 mesenchymal cell line on polished or acid‐etched, sand‐blasted (SLA) commercially pure titanium. When we transfected cells with Wnt3a or wild‐type β‐catenin and a reporter construct, we found that stimulation of Wnt canonical signaling was enhanced in cells on SLA surfaces. Moreover, more β‐catenin translocated to the nucleus in cells on SLA surfaces after stimulation with Wnt3a as evidenced by immunofluorescence. However, when cells were transfected with constitutively active S33Y β‐catenin mutant, no difference was observed between the groups. Higher levels of transcripts of Wnt target genes were detected in C2C12 cells cultured on SLA surfaces following transfection with Wnt3a, but the expression of a gene regulating β‐catenin degradation, Axin 2, was reduced on SLA surfaces. Inhibition of β‐catenin mediated transcription by dnTCF in murine osteoblastic MC3T3 cells, reversed the effects of topography on cell differentiation. Taken together, these results show that surface roughness modulates the responsiveness of mesenchymal cells to Wnt3a, that this requires the control of β‐catenin degradation, and that the control of β‐catenin signaling by surface topography is accountable for at least part of the effects of surface on cell differentiation. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
In vitro hydrolytic and enzymatic degradation of nestlike‐patterned electrospun poly(D,L‐lactide‐co‐glycolide) scaffolds
Authors: Zhou Xuegang , Cai Qing , Yan Na , Deng Xuliang , Yang Xiaoping
Published: August 2010

A common problem in applying electrospun biodegradable polyester matrixes as tissue‐engineering scaffolds is their serious shrinkage with degradation to reduce the porosity drastically. To ameliorate this problem, a nestlike‐patterned poly(D,L‐lactide‐co‐glycolide) (PLGA) nanofibrous (∼900 nm) matrix was proposed and fabricated by electropinning. Shrinkage studies demonstrated that the dimension change of nestlike‐patterned fibrous membrane was much smaller than those of nonwoven and parallel‐aligned fibrous membranes. And the robust framework of the patterned matrix helped to maintain its original nestlike topographical structure during degradation. Compared to hydrolytic‐degraded specimens, the PLGA nanofibrous matrixes degraded in the presence of lysozyme showed larger weight loss but slower decrease in molecular weight. Besides, porous fibers with intact surface were detected by scanning electron microscopy after 20‐week hydrolysis, and fibers with pores both inside and on surface were observed after enzymatic degradation for 12 weeks. Accordingly, the former presented a bimodal gel permeation chromatography (GPC) peak, while no bi or multimodal GPC peaks were found for the latter as degradation proceeded. These results indicated that an acid autocatalytic effect still existed in the hydrolysis of PLGA nanofibrous matrix. The presence of lysozyme could only accelerate the dissolution of degradation products with low molecular weight, but have no contribution to the chain scission. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Effects of VEGF loading on scaffold‐confined vascularization
Authors: Lindhorst Daniel , Tavassol Frank , von See Constantin , Schumann Paul , Laschke Matthias W. , Harder Yves , Bormann Kai‐Hendrik , Essig Harald , Kokemüller Horst , Kampmann Andreas , Voss André , Mülhaupt Rolf , Menger Michael D. , Gellrich Nils‐Claudius , Rücker Martin
Published: August 2010

Adequate vascularization of tissue‐engineered constructs remains a major challenge in bone grafting. In view of this, we loaded ß‐tricalcium‐phosphate (ß‐TCP) and porous poly(L‐lactide‐co‐glycolide) (PLGA) scaffolds via collagen coating with vascular endothelial growth factor (VEGF) and studied whether the VEGF loading improves scaffold angiogenesis and vascularization. Dorsal skinfold chambers were implanted into 48 balb/c mice, which were assigned to 6 groups (n = 8 each). Uncoated (controls), collagen‐coated, and additionally VEGF‐loaded PLGA and ß‐TCP scaffolds were inserted into the chambers. Angiogenesis, neovascularization, and leukocyte‐endothelial cell interaction were analyzed repeatedly during a 14‐day observation period using intravital fluorescence microscopy. Furthermore, VEGF release from PLGA und ß‐TCP scaffolds was studied by ELISA. Micromorphology was studied from histological specimens. Unloaded ß‐TCP scaffolds showed an accelerated and increased angiogenic response when compared with unloaded PLGA scaffolds. In vitro, PLGA released significantly higher amounts of VEGF compared with ß‐TCP at the first two days resulting in a rapid drop of the released amount at the following days up to day 7 where the VEGF release was negligible. Nonetheless, in vivo VEGF loading increased neovascularization, especially in ß‐TCP scaffolds. This increased vascularization was associated with a temporary leukocytic response with pronounced leukocyte‐endothelial cell interaction at days 3 and 6. Histology revealed adequate host tissue response and engraftment of both ß‐TCP and PLGA scaffolds. Our study demonstrates that ß‐TCP scaffolds offer more suitable conditions for vascularization than PLGA scaffolds, in particular if they are loaded with VEGF. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.