bluuebunny/crossref_metadata_2025 huggingface dataset:
Route‐dependent stereoselective pharmacokinetics of tramadol and its activeO‐demethylated metabolite in rats
Authors: Parasrampuria Ridhi , Vuppugalla Ragini , Elliott Katherine , Mehvar Reza
Published: December 2006

The effects of route of administration on the stereoselective pharmacokinetics of tramadol (T) and its active metabolite (M1) were studied in rats. A single 20 mg/kg dose of racemic T was administered through intravenous, intraperitoneal, or oral route to different groups of rats, and blood and urine samples were collected. Samples were analyzed using chiral chromatography, and pharmacokinetic parameters (mean ± SD) were estimated by noncompartmental methods. Following intravenous injection, there was no stereoselectivity in the pharmacokinetics of T. Both enantiomers showed clearance values (62.5 ± 27.2 and 64.4 ± 39.0 ml/min/kg for (+)‐ and (−)‐T, respectively) that were equal or higher than the reported liver blood flow in rats. Similar to T, the area under the plasma concentration–time curves (AUCs) of M1 did not exhibit stereoselectivity after intravenous administration of the parent drug. However, the systemic availability of (+)‐T was significantly (P< 0.05) higher than that of its antipode following intraperitoneal (0.527 ± 0.240 vs. 0.373 ± 0.189) and oral (0.307 ± 0.136 vs. 0.159 ± 0.115) administrations. The AUC of the M1 enantiomers, on the other hand, remained mostly nonstereoselective regardless of the route of administration. Pharmacokinetic analysis indicated that the stereoselectivity in the pharmacokinetics of oral T is due to stereoselective first pass metabolism in the liver and, possibly, in the gastrointestinal tract. The direction and extent of stereoselectivity in the pharmacokinetics of T and M1 in rats were in agreement with those previously reported in humans, suggesting that the rat may be a suitable model for enantioselective studies of T pharmacokinetics. Chirality, 2007. © 2006 Wiley‐Liss, Inc.
Understanding Binding Selectivity toward Trypsin and Factor Xa: the Role of Aromatic Interactions
Authors: Di Fenza Armida , Heine Andreas , Koert Ulrich , Klebe Gerhard
Published: December 2006

A congeneric series of four bis‐benzamidine inhibitors sharing a dianhydrosugar isosorbide scaffold in common has been studied by crystal structure analysis and enzyme kinetics with respect to their binding to trypsin and factor Xa. Within the series, aromatic interactions are an important determinant for selectivity discrimination among both serine proteases. To study the selectivity‐determining features in detail, we used trypsin mutants in which the original binding site is gradually substituted to finally resemble the factor Xa binding pocket. The influence of these mutations has been analyzed on the binding of the closely related inhibitors. We present the crystal structures of the inhibitor complexes obtained by co‐crystallizing an “intermediate” trypsin mutant. They could be determined to a resolution of up to 1.2 Å, and we measured the inhibitory activity (Ki) of each ligand against factor Xa, trypsin, and the various mutants. From these data we were able to derive a detailed structure–activity relationship which demonstrates the importance of aromatic interactions in protein–ligand recognition and their role in modulating enzyme selectivity. Pronounced preference is experienced to accommodate the benzamidine anchor withmetatopology in the S1specificity pocket. One ligand possessing onlyparatopology deviates strongly from the other members of the series and adopts a distinct binding mode addressing the S1′ site instead of the distal S3/S4binding pocket.
Characterisation of the Binding of Cationic Amphiphilic Drugs to Phospholipid Bilayers Using Surface Plasmon Resonance
Authors: Nussio Matthew R. , Sykes Matthew J. , Miners John O. , Shapter Joseph G.
Published: December 2006

The interactions of three cationic amphiphilic drugs (CPZ, AMI, PROP) with phospholipid vesicles comprising DOPC, DMPC, or DSPC were investigated using surface plasmon resonance (SPR). Responses for CAD concentrations in the range 15.625 to 1500 μM were measured. The greatest uptake by each phospholipid bilayer occurred with CPZ. Inclusion of CAD concentrations between 750 and 1500 μM provided evidence for a second nonsaturable binding process, which may arise from intercalation of the drugs within the lipid bilayer. CAD binding was additionally shown to be dependent on membrane fluidity. Responses were initially fitted over a concentration range of 15.625 to 500 μM using a model which incorporated terms for a saturable binding site. This yielded very poor values of KD and nonsensible values of saturation responses. Subsequently, responses were fit to the expression for a model which incorporated terms for both a saturable binding site and second nonsaturable site. Measurable binding affinities (KD values ranged from 170 to 814 μM) were obtained for DOPC and DMPC bilayers which are similar to values reported previously. This work demonstrates that SPR studies with synthetic phospholipid bilayers provide a potentially useful approach for characterising drug–membrane binding interactions and for providing insight into the processes that contribute to drug–membrane binding.
Cover Picture: Simulating α/β Selectivity at the Human Thyroid Hormone Receptor: Consensus Scoring Using Multidimensional QSAR (ChemMedChem 1/2007)
Authors: Vedani Angelo , Zumstein Martin , Lill Markus A. , Ernst Beat
Published: December 2006

The cover picture shows various representations of a 3,5‐dibromophenyl acetic acid analogue that is highly active (0.47 nM) toward the thyroid receptor β subtype. On the left, a space‐filling model depicts the bioactive conformation of the ligand as identified trough flexible docking to the X‐ray crystal structure. On the right, a 3D receptor surrogate (as generated by the Raptor technology) used to quantify the binding affinity in silico displays two layers of quasi‐atomistic properties representing the binding pocket and explicitly allowing for the simulation of induced fit. Overlaid is a ribbon representation of the true biological receptor, which served as a template for the docking studies. For more details, see the Full Paper by A. Vedani et al. on p. 78 ff.
Hofmeister Effects on Poly(NIPAM) Microgel Particles: Macroscopic Evidence of Ion Adsorption and Changes in Water Structure
Authors: López‐León Teresa , Elaïssari Abdelhamid , Ortega‐Vinuesa Juan Luis , Bastos‐González Delfi
Published: December 2006

The term Hofmeister effects is broadly used to refer to ionic specificities in many different physical, chemical and biological phenomena. The origin of this ionic specificity is sought in two interdependent microscopic sources: 1) the peculiarities of the solvent structure near surfaces and around the ions, and 2) specific ion adsorption–exclusion mechanisms near a surface. In this work, Hofmeister effects on poly(N‐isopropylacrylamide) [poly(NIPAM)]‐based microgels are examined. Poly(NIPAM) particles are thermally sensitive microgels exhibiting volume‐phase transitions with temperature. This temperature‐sensitive system seems to be suitable for the independent observation of the two microscopic sources of Hofmeister effects. On the one hand, volume‐phase transition, evaluated by photon correlation spectroscopy (PCS), gives information about how the presence of ions changes the water structure around the poly(NIPAM) chains. On the other hand, electrokinetic studies show relevant data about ionic adsorption–exclusion phenomena at the polymer surface.
Cloning and characterization of scale β‐keratins in the differentiating epidermis of geckoes show they are glycine‐proline‐serine–rich proteins with a central motif homologous to avian β‐keratins
Authors: Dalla Valle Luisa , Nardi Alessia , Toffolo Vania , Niero Cristiana , Toni Mattia , Alibardi Lorenzo
Published: December 2006

The β‐keratins constitute the hard epidermis and adhesive setae of gecko lizards. Nucleotide and amino acid sequences of β‐keratins in epidermis of gecko lizards were cloned from mRNAs. Specific oligonucleotides were used to amplify by 3′‐ and 5′‐rapid amplification of cDNA ends analyses five specific gecko β‐keratin cDNA sequences. The cDNA coding sequences encoded putative glycine‐proline‐serine–rich proteins of 16.8–18 kDa containing 169–191 amino acids, especially 17.8–23% glycine, 8.4–14.8% proline, 14.2–18.1% serine. Glycine‐rich repeats are localized toward the initial and end regions of the protein, while a central region, rich in proline, has a strand conformation (β‐pleated fold) likely responsible for the formation of β‐keratin filaments. It shows high homology with a core region of other lizard keratins, avian scale, and feather keratins. Northern blotting and reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis show a higher β‐keratin gene expression in regenerating epidermis compared with normal epidermis. In situ hybridization confirms that mRNAs for these proteins are expressed in cells of the differentiating oberhautchen cells and β‐cells. Expression in adhesive setae of climbing lamellae was shown by RT‐PCR. Southern blotting analysis revealed that the proteins are encoded by a multigene family. PCR analysis showed that the genes are presumably located in tandem along the DNA and are transcribed from the same DNA strand like in avian β‐keratins. Developmental Dynamics 236:374–388, 2007. © 2006 Wiley‐Liss, Inc.
Temporomandibular joint formation and condyle growth require Indian hedgehog signaling
Authors: Shibukawa Yoshihiro , Young Blanche , Wu Changshan , Yamada Satoru , Long Fanxin , Pacifici Maurizio , Koyama Eiki
Published: December 2006

The temporomandibular joint (TMJ) is essential for jaw function, but the mechanisms regulating its development remain poorly understood. Because Indian hedgehog (Ihh) regulates trunk and limb skeletogenesis, we studied its possible roles in TMJ development. In wild‐type mouse embryos, Ihh expression was already strong in condylar cartilage by embryonic day (E) 15.5, and expression of Ihh receptors and effector genes (Gli1, Gli2, Gli3, and PTHrP) indicated that Ihh range of action normally reached apical condylar tissue layers, including polymorphic chondroprogenitor layer and articular disc primordia. In Ihh−/− embryos, TMJ development was severely compromised. Condylar cartilage growth, polymorphic cell proliferation, and PTHrP expression were all inhibited, and growth plate organization and chondrocyte gene expression patterns were abnormal. These severe defects were partially corrected in double Ihh−/−/Gli3−/− mutants, signifying that Ihh action is normally modulated and delimited by Gli3 and Gli3R in particular. Both single and double mutants, however, failed to form an articular disc primordium, normally appreciable as an independent condensation between condylar apex and neighboring developing temporal bone in wild‐type. This failure persisted at later stages, leading to complete absence of a normal functional disc and lubricin‐expressing joint cavities. In summary, Ihh is very important for TMJ development, where it appears to regulate growth and elongation events, condylar cartilage phenotype, and chondroprogenitor cell function. Absence of articular disc and joint cavities in single and double mutants points to irreplaceable Ihh roles in formation of those critical TMJ components. Developmental Dynamics 236:426–434, 2007. © 2006 Wiley‐Liss, Inc.
Differential gene expression patterns in porcine nuclear transfer embryos reconstructed with fetal fibroblasts and mesenchymal stem cells
Authors: Kumar B. Mohana , Jin Hai‐Feng , Kim Jung‐Gon , Ock Sun‐A , Hong Yonggeun , Balasubramanian S. , Choe Sang‐Yong , Rho Gyu‐Jin
Published: December 2006

The present study compared the developmental ability and gene expression pattern at 4‐cell, 8‐cell, morula, and blastocyst stages of porcine nuclear transfer (NT) embryos from fetal fibroblasts (FFs) and mesenchymal stem cells (MSCs), in vitro fertilized (IVF), and in vivo derived embryos. MSC‐NT embryos showed enhanced blastocyst formation, higher total cell number, and a low incidence of apoptosis compared to FF‐NT embryos. Alterations in the expression pattern of genes implicated in transcription and pluripotency (Oct4, Stat3, Nanog), DNA methylation (Dnmt1, Dnmt3a), histone deacetylation (Hdac2), growth factor signaling, and imprinting (Igf2, Igf2r) and apoptosis (Bax, Bcl2) regulation were observed in NT embryos. The expression of transcripts in MSC‐NT embryos more closely followed that of the in vivo derived embryos compared with FF‐NT embryos. In conclusion, MSCs with a relatively undifferentiated genome might serve as suitable donors that could be more efficiently reprogrammed to re‐activate expression of early embryonic genes in porcine NT. Developmental Dynamics 236:435–446, 2007. © 2006 Wiley‐Liss, Inc.
Two‐dimensional and three‐dimensional time‐lapse microscopic magnetic resonance imaging of Xenopus gastrulation movements using intrinsic tissue‐specific contrast
Authors: Papan Cyrus , Boulat Benoit , Velan S. Sendhil , Fraser Scott E. , Jacobs Russell E.
Published: December 2006

The amphibian embryo undergoes radical tissue transformations during blastula and gastrula stages, but live observation of internal morphogenetic events by optical microscopy is not feasible due to the opacity of the early embryo. Here, we report on the use of microscopic magnetic resonance imaging (MRI) to directly follow morphogenetic movements during blastula and gastrula stages of the Xenopus laevis embryo. We compare three different MRI modalities that take advantage of the intrinsic contrast present in embryonic tissues: three‐dimensional (3D) fat‐imaging, 3D water‐imaging, and 2D high‐speed high‐resolution imaging of early embryonic stages. We show that the features revealed by the intrinsic contrast correlate with the histological structure of the embryo. Using this tissue specific intrinsic contrast, the main embryonic tissues and internal tissue movements as well as archenteron invagination can be differentiated without cell labeling. We present 2D and 3D time‐lapse sequences of early Xenopus embryonic development, spanning the stages from early blastula to the end of gastrula, which show the complex internal rearrangements of gastrulation in essentially real‐time. Developmental Dynamics 236:494–501, 2007. © 2006 Wiley‐Liss, Inc.
Maternally imprinted microRNAs are differentially expressed during mouse and human lung development
Authors: Williams Andrew E. , Moschos Sterghios A. , Perry Mark M. , Barnes Peter J. , Lindsay Mark A.
Published: December 2006

MicroRNAs (miRNAs) are a recently discovered class of noncoding genes that regulate the translation of target mRNA. More than 300 miRNAs have now been discovered in humans, although the function of most is still unknown. A highly sensitive, semiquantitative real‐time polymerase chain reaction method was used to reveal the differential expression of several miRNAs during the development of both mouse and human lung. Of note was the up‐regulation in neonatal mouse and fetal human lung of a maternally imprinted miRNA cluster located at human chromosome 14q32.31 (mouse chromosome 12F2), which includes the miR‐154 and miR‐335 families and is situated within the Gtl2‐Dio3 domain. Conversely, several miRNAs were up‐regulated in adult compared with neonatal/fetal lung, including miR‐29a and miR‐29b. Differences in the spatial expression patterns of miR‐154, miR‐29a, and miR‐26a was demonstrated using in situ hybridization of mouse neonatal and adult tissue using miRNA‐specific locked nucleic acid (LNA) probes. Of interest, miR‐154 appeared to be localized to the stroma of fetal but not adult lungs. The overall expression profile was similar for mouse and human tissue, suggesting evolutionary conservation of miRNA expression during lung development and demonstrating the importance of maternally imprinted miRNAs in the developmental process. Developmental Dynamics 236:572–580, 2007. © 2006 Wiley‐Liss, Inc.
Modeling of a high‐speed polarization controller based on a vertical‐cavity surface‐emitting laser
Authors: Hasebe Koichi , Onishi Yutaka , Koyama Fumio
Published: December 2006

Photonic networks have gained attention as the next generation optical communication system because their communication processes use wavelength information in the optical region. Generally, because the polarization states of the optical wavelengths propagating in optical fibers are irregular, strong noise is generated because the optical devices constructing the photonic network exhibit a dependence on polarized light. To suppress this noise, polarization control becomes an important technology. In this research, we propose a new polarization controller to bring out the superior features of the surface‐emitting laser and examine its dynamic characteristics. In this paper, we also conduct analysis based on the multimode rate equations that consider high‐order lateral modes and polarization modes, and dynamic analysis of the polarization controller based on analyzing the optical inverter characteristics obtained by the lateral mode switching, which becomes the fundamental principle of the light input and output. Based on the static and dynamic characteristics, we demonstrated the possibility of a high‐speed polarization controller using a surface‐emitting laser structure. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(1): 41– 49, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20258
Heavy‐ion induced current in MOS structure
Authors: Takahashi Yoshihiro , Shibata Toshihiko , Ohnishi Kazunori , Hirao Toshio , Onoda Shinobu , Kamiya Tomihiro
Published: December 2006

We studied the mechanism for generation of transient current in MOS structures during heavy‐ion irradiation. In heavy‐ion (argon, oxygen) irradiation tests on Al gate MOS diodes, we observed irradiation‐induced transient current only in bias conditions where the semiconductor surface is in a depletion condition, and found that the peak value was dependent on the applied voltage during irradiation, the oxide film thickness, and the linear energy transfer of heavy ion. In addition, in a comparison of calculation results and test results using a device simulation, we found that a model of the oxide film as a perfectly insulating film can be used to quantitatively explain the test results, and confirmed that the displacement current component of the heavy‐ion induced current in the MOS structure transmitted via the oxide film is dominant. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(1): 32–40, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20274
Theoretical analysis of tunneling phenomenon in asymmetrical triple‐barrier structures with outer wells
Authors: Takura Hiroyuki , Yamamoto Hiroaki
Published: December 2006

The impact of the outer wells on tunneling characteristics is theoretically studied in a new structure with outer wells consisting of wells on both sides of an asymmetrical triple barrier structure. First, the theoretical equation for the transmission coefficient is derived and the resonance conditions are studied. It is found that resonance is not related to the existence of the outer wells and is governed by the two resonance conditions independently existing in the two wells between the barriers. Second, the dwell time of electrons at the two resonant energy values is analyzed. The dwell time in the triple barrier structure with outer wells is compressed to about 14% at the maximum in comparison with the dwell time in the triple barrier structure without outer wells. Even if the dwell time is compared with that in the structure with a prewell, which is a conventional way of reducing the dwell time, a reduction to about 60% is realized. Also, with regard to the current density versus voltage characteristics for the structure with outer wells, it is found that a large current flows at a lower voltage than in the structure without outer wells. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(1): 20–31, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20275
The frequency adjustment method of quartz crystal unit using a quick response evaporation source
Authors: Shiono Tadahisa , Kubo Shinichi , Ito Makoto , Shimizu Yasuhito , Tsuchikura Kazuo
Published: December 2006

In the manufacture of quartz crystal units, there is a frequency adjustment process in which the individual frequencies are measured and matched to each other, resulting in a frequency adjustment method based on the use of a resistance heating evaporation source to deposit Ag, Au, and other electrode materials. The frequency measurement method used for quartz crystal units has been the oscillation method, and we proposed a transmission method based on a network analyzer and π circuit to improve measurement precision, and a standby method based on a CW sweep to increase measurement speed. We then developed a quick response evaporation source control method adapted for the proposed method. Because the CW sweep standby method sweeps only one point, measurement can be performed in a shorter time than with a linear sweep. In addition, since we were able to perform high‐precision adjustment in a short time, we implemented rate switching, starting adjustment at a high rate and finishing at a low rate, and then controlled the evaporation source so that the rate remained fixed during standby time. As a result, we were able to switch the rate in three stages for a normal frequency adjustment volume of about 1000 ppm, achieving adjustment of ±2 ppm during the deposition time of 2.5 seconds. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(1): 11–19, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20282
Miniaturized branch‐line hybrid circuit using 3D MMIC quasi‐distributed TFMS lines
Authors: Tanaka Takayuki , Nishikawa Kenjiro , Aikawa Masayoshi
Published: December 2006

This paper discusses a miniaturized branch‐line hybrid circuit consisting of quasi‐distributed TFMS lines, making use of the topological characteristics of the three‐dimensional MMIC. In the three‐dimensional MMIC, it is possible to reduce the coupling between adjacent transmission lines due to their very fine structure. Hence, miniaturized meander‐like lines can easily be realized. Further, due to the stacking effect in this technique, MIM (metal–insulator–metal) capacitors can easily be installed into the transmission line. In this paper, by utilizing these effects, a transmission line consisting of high‐impedance TFMS lines and MIM capacitors is proposed. The TFMS line of this type is here called a QD‐TFMS (Quasi‐Distributed Thin Film MicroStrip) line. First, the characteristics of the QD‐TFMS line are obtained by simulation and the size reduction effect is verified. Further, miniaturization of the branch‐line hybrid circuit using the QD‐TFMS lines is discussed. It is demonstrated that the fabricated circuit can be miniaturized to an area ratio of less than 20% in comparison with a branch‐line hybrid circuit using only meander‐like lines. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(1): 1–10, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20291
Inverse reflectometry for real objects with diffuse and specular interreflections
Authors: Machida Takashi , Takemura Haruo , Yokoya Naokazu
Published: December 2006

In the study of composite reality, in which virtual objects are synthesized and displayed in a real environment, intensive research is under way on virtual reality in order to achieve the virtual representation of real objects with a greater resemblance to reality. The estimation of the surface reflection characteristics of the object is especially important in order to eliminate inconsistencies of shadow between the real environment and the virtual object. To deal with this problem, we are continuing the study of dense estimation of the reflection characteristics of objects from distant images and surface texture images. For objects of complex shape, we have proposed a method of taking account of the effect of mutual reflection due to the secondary reflections on the object surface. However, there remains the problem that the effect of mutual reflection by specular‐reflection components cannot be eliminated. Consequently, a method is proposed in this paper which estimates the reflectance with allowance for the effect of mutual reflection, including the specular reflection component on the object surface. Specifically, the method is as follows. First, the illumination conditions with regard to the direction of illumination are determined from the object shape in order to observe the reflection component at a large number of points on the object surface. Based on the determined multiple illumination conditions and the measured data, photon mapping is applied, using the photon distribution on the object surface to estimate the surface reflectance at each point on the surface. In experiments, the estimated reflectance is compared to the results obtained by conventional methods, and it is shown that the proposed method can represent objects faithfully under various illumination conditions in the virtual environment. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(1): 50–60, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20324
Interference fringe pattern analysis using inverse cosine function
Authors: Okada Koichi , Yokoyama Etsuro , Miike Hidetoshi
Published: December 2006

The analysis of interference fringe patterns is a technique which is indispensable in estimating the shape of an object or the refractive index field of a solution from the interference fringe pattern image. In the methods proposed to date, however, satisfactory analysis has been difficult in situations where the image contains only a few fringes, the object shape is not smooth, or the target of measurement is continuously changing with time. This paper proposes the following method of analysis. The inverse cosine function (arccos function) is applied to the interference fringe pattern image after normalizing the intensity. Then the phase inversion is estimated by assuming a monotonically increasing phase. The method is a combination of simple ideas derived from the principles of interference fringe patterns, but can be used to calculate the phase for each pixel from a single interference fringe pattern image. Depending on the conditions, analysis with higher temporal and spatial resolutions than in the Fourier transform method can be achieved. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(1): 61–73, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20325
Synthesis and Oxidation of Vanadyl Complexes Containing Bispidine Ligands
Authors: Comba Peter , Kuwata Shigemasa , Linti Gerald , Tarnai Máté , Wadepohl Hubert
Published: December 2006

The reaction of 3‐methyl‐9‐oxo‐7‐picolyl‐2,4‐di(2‐pyridyl)‐3,7‐diazabicyclo[3.3.1]nonane‐1,5‐dicarboxylate (L2) with vanadyl sulfate in methanol yields the purple complex[VIV=O(L2′)](ClO4)2, where L2 is hydrated to the corresponding 9‐diol L2′. The crystal structure of [VIV=O(L2′)](ClO4)2 has a saturated coordination sphere with a long bond to the tertiary amine N7 trans to the oxido group (2.36 Å). Oxidation of [VIV=O(L2′)](ClO4)2 with an excess of aqueous hydrogen peroxide yields the orange complex [VV=O(O2)(L2′)]ClO4. This can be further oxidized with Ce4+ in MeCN at –40 °Cto the unstable vanadium(V)‐oxidosuperoxido complex [VV=O(O2)(L2′)]2+, as shown by EPR spectroscopy. The X‐ray crystal structure of [VV=O(O2)(L2′)]ClO4 shows that the N7‐pendant pyridine donor is dissociated and the V–N7 bond is elongated (2.56 Å). The O–O distance of the side‐on bound peroxide in [VV=O(O2)(L2′)]ClO4 is unexpectedly short (1.28 Å) and is therefore in the range which is typical for a superoxido group. However, the IR spectrum of [VV=O(O2)(L2′)]ClO4 shows 18O isotope shifts, which support the assignment as a peroxido complex, and this is also supported by EPR and UV/Vis spectroscopic analysis. The short O–O bond is attributed to a static disorder rather than to libration of the “non‐rigid” peroxido group.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Use of poly(vinyl alcohol)‐coated capillaries for separation of amino‐terminated polyamidoamine dendrimers
Authors: Carter Britton , Desai Ankur , Sharma Ajit
Published: December 2006

Characterization of amino‐terminated polyamidoamine dendrimers by CE suffers from a lack of resolution for higher generations and poor between‐day reproducibility of retention times. Under optimal conditions of temperature, voltage, and sample amount, 0–5 generations of dendrimers could be resolved with a bare fused‐silica capillary. However, reproducibility was poor due to potential interactions of the polycationic dendrimers with the uncoated quartz capillary wall. Use of a poly(vinyl alcohol)‐coated capillary significantly decreased the migration times of the nanomolecules without compromising resolution. Dendrimer mixtures containing generations 0–5 are separated as discrete, nonoverlapping peaks in about 15 min. In addition, the between‐day precision of retention times was dramatically improved without the need for internal standards or data normalization. Dendrimers of various generations and cores run on different days showed an RSD of retention times of less than 4%. The poly(vinyl alcohol) coating was very stable as shown by the excellent precision of migration times obtained on a capillary used for a month with more than 100 injections. Similar to PAGE, separation of polyamidoamine dendrimers on a bare fused‐silica and poly(vinyl alcohol)‐coated capillary showed an exponential relationship between migration times and calculated charge density of the nanomolecules.
Simulation of DNA electrophoresis through microstructures
Authors: Maleki‐Jirsaraei Nahid , Sarbolouki Mohamad‐Nabi , Rouhani Shahin
Published: December 2006

The dependence of the mobility of DNA molecules through an hexagonal array of micropillars on their length and the applied electric field was investigated and it was found that mobility is a nonmonotonic function of their length. Results also revealed that the size dependence of the DNA mobility depends on the applied electric field and there is a crossover around E ≈ 25 V/cm for the mobility of λ‐DNA and T4‐DNA. These observations are explained in terms of the diffusion process inside the structure affected by the solvent and are modeled using the Langevin and its corresponding Fokker–Planck equations. The phenomenon is generalized under three regimes in a phase diagram relating the electric field and the DNA lengths. The model and the associated phase diagram described here provide an explanation for the conflicting results reported by previous authors (Han et al. on the one hand, and Duong et al. and Inatomi et al. on the other) about the dependence of mobility on the DNA size in lattices near or below the radius of gyration.
Construction of an antibody microarray based on agarose‐coated slides
Authors: Lv Lin‐Li , Liu Bi‐Cheng , Zhang Chun‐Xiu , Tang Zu‐Ming , Zhang Lu , Lu Zu‐Hong
Published: December 2006

The antibody microarray, a high‐throughput multiplex immunoassay method, has become a significant tool for quantitative proteomics studies. We describe here the strategies for optimizing the condition of antibody microarray building based on agarose‐coated slides. In this study, modified glass slides were robotically printed with capture antibodies against monocyte chemoattractant protein 1 (MCP‐1), then dilutions of the cytokine were applied to the arrays, and the protein was detected with biotin‐labeled antibody coupled with Cy3‐conjugated streptavidin. Thus a protein profiling microarray based on sandwich immunoassay has been established. Various factors in the production of antibody microarrays were analyzed: the capture antibody concentrations, shelf life of the postprinting slides, blocking buffers, and reproducibility of the system. A calibration curve with a correlation coefficient of 0.9995 was established which suggested that the matrix can retain arrayed proteins in near‐quantitative fashion. The results revealed high signal uniformity and reproducibility with regard to intra‐array (1.3%) and the interarray (8.7%) variation at the capture antibody concentration of 125 µg/mL. Besides, the printed arrays could be stored for at least two months without any apparent change of the performance parameters.
Rapid characterization of alkylpolyphosphonates by CZE with indirect photometric and mass spectrometric detection
Authors: Bernabé‐Zafón Virginia , Micó‐Tormos Anna , Simó‐Alfonso Ernesto F. , Ramis‐Ramos Guillermo
Published: December 2006

Methods for the rapid characterization of industrial alkylpolyphosphonates (APPs) by infusion MS and CZE with indirect photometric (IPD) and MS detection are described. Technical‐grade APPs, including alkylaminepolyphosphonates with 3–5 phosphonate groups and different hydrocarbon skeletons, hydroxyethyl‐amino‐bis(methylenephosphonic acid), hydroxyethylidene‐diphosphonic acid, and 2‐phosphonobutane‐1,2,4‐tricarboxylic acid, were examined. A 10 mM solution of adenosine triphosphate disodium salt at pH 2.2 was used as BGE. The nominal compounds of the industrial APPs and their impurities were well resolved in less than 15 min. The peaks were identified by using extracted ion electropherograms, which were obtained at the m/z values indicated by the peaks of the infusion spectra. Low concentrations of esters, anhydrides, and APPs having different hydrocarbon skeletons compared to nominal compounds, and lacking phosphonate and methylene‐phosphonate groups with respect to them, were found. Also, hydroxyethyl‐aminobis(methylenephosphonic acid) contained an intramolecular ester at a concentration close to that of the nominal compound. Application of CZE‐IPD and CZE‐MS to the quality control of industrial APPs, and of CZE‐MS to the identification and characterization of APPs in cleaning products, was demonstrated.
A re‐examination of distance as a proxy for severity of illness and the implications for differences in utilization by race/ethnicity
Authors: Basu Jayasree , Friedman Bernard
Published: December 2006

The study analyzes the hospitalization patterns of elderly residents to examine whether the relation between distant travel and severity of illness is uniform across racial/ethnic subgroups. A hypothesis is made that severity thresholds could be higher for minorities than whites. Hospital discharge data from the Healthcare Cost and Utilization Project (HCUP‐SID) of the Agency for Health Care Research and Quality for New York residents is used, with a link to the Area Resource File and American Hospital Association's survey files. Logistic models compare the association of distant admission with severity corresponding to each local threshold level, race, and type of hospital admission. The study uses four discrete distance thresholds in contrast to recent work. Also, an examination of severity thresholds for distant travel for different types of admission may clarify different sources of disparities in health care utilization. The findings indicate that minorities are likely to have higher severity thresholds than whites in seeking distant hospital care, although these conclusions depend on the type of condition. The study results imply that if costly elective services were regionalized to get the advantages of high volume for both cost and quality of care, some extra effort at outreach may be desirable to reduce disparities in appropriate care. Published in 2006 by John Wiley & Sons, Ltd.
Major depression‐related immunological changes and combination antiretroviral therapy in HIV‐seropositive patients
Authors: Alciati Alessandra , Gallo Luciana , Monforte Antonella D'Arminio , Brambilla Francesca , Mellado Carmen
Published: December 2006

Background

In physically healthy subjects, major depression has been associated with several changes in immune function. In HIV‐infected subjects too, lymphocyte subsets changes related to psychological conditions have been described.

Objective

The aim of this study was to investigate the effect of major depression on immunological parameters in HIV‐infected subjects and to examine the influence of different potency antiretroviral therapies on depression‐related immunological changes.

Method

Thirty‐six HIV‐infected patients with major depression treated with different potency antiretroviral therapies (none, double, triple) were compared with 77 matched non‐depressed HIV controls with regard to demographic, clinical and immunological parameters.

Results

The presence of depression was a significant predictor of natural killer (NK) cell number and percentage decline. Antiretroviral therapy and depression‐antiretroviral therapy interaction do not significantly influence depression‐related NK cell changes.

Conclusions

The study confirms the role of depression in influencing the immune response in HIV‐seropositive subjects and suggests that antiretroviral therapies may not be able to hamper the depression‐related NK cell changes even using the most potent regimens such as Highly Active Antiretroviral Therapy (HAART). Copyright © 2007 John Wiley & Sons, Ltd.
Venlafaxine induces P‐glycoprotein in human Caco‐2 cells
Authors: Ehret M. J. , Levin G. M. , Narasimhan M. , Rathinavelu A.
Published: December 2006

Purpose

The objective of this study was to evaluate the effect of a treatment with venlafaxine on the expression of multidrug resistance‐associated protein (MRP) gene and multidrug resistance‐related proteins (MDR) in human colon carcinoma cells (Caco‐2) compared to a known P‐glycoprotein (PGY1) inducer, rifampine.

Methods

Caco‐2 cells were treated with venlafaxine (50 µM, 100 µM, 250 µM, and 500 µM) and rifampin (25 µM and 50 µM) to test the possible induction of MRP and MDR expression. The treatment times used were 1.5, 3, 6, 12, 24, 48, and 72 h. RNA was isolated from the cells, and MDR and MRP genes were amplified using PCR.

Results

Both venlafaxine and rifampine had the most dramatic effect at the 50 µM concentration. There was an increase in MDR and MRP expression in Caco‐2 cells after the acute treatment (1.5, 3, and 6 h) with venlafaxine. These results were similar to those with rifampine.

Conclusions

PGY1 contributes to renal and biliary elimination of drugs by transporting the drug out of the cell and back into the intestinal lumen, where drugs may be further metabolized by intestinal enzymes such as Cytochrome P (CYP)‐450 3A4. Its function is to limit the bioavailability of orally administered compounds. Due to the increase in MDR and MRP gene expression seen after the acute treatment with venlafaxine, there could be a potential drug–drug interaction with other medications that are metabolized via CYP450–3A4 when coadministered with venlafaxine. Copyright © 2007 John Wiley & Sons, Ltd.
Clinical correlates of clozapine prescription for schizophrenia in China
Authors: Xiang Yu‐tao , Weng Yong‐zhen , Leung Chi‐Ming , Tang Wai‐Kwong , Ungvari Gabor Sandor
Published: December 2006

Aims

Few studies have investigated the prescription patterns of clozapine in outpatients with schizophrenia in China. It is an important issue due to clozapine's high efficacy and potentially fatal side effect profile. This study examined the use of clozapine and its correlates in China.

Methods

Three hundred ninety‐eight clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong (HK) and Beijing (BJ). Assessment instruments included the Structured Clinical Interview for DSM‐IV, Brief Psychiatric Rating Scale, Simpson and Angus Scale of Extrapyramidal Symptoms, Barnes Akathisia Rating Scale and the Hong Kong and Mainland China World Health Organization Quality of Life Schedule‐Brief version. Assessments were performed by the same investigator in both sites.

Results

Clozapine was prescribed to 15.6% of (n = 62) patients. There was a wide inter‐site variation between HK and BJ. Use of clozapine was associated with age, age at onset, extrapyramidal side effects (EPS), having health insurance, use of depot and typical antipsychotic and anticholinergic drugs and benzodiazepines as well as history of suicidal attempts. On multiple logistic regression analysis, the number of hospitalizations, site (HK vs. BJ), use of typical antipsychotics, polypharmacy and co‐prescription with anticholinergics were significantly associated with the prescription of clozapine. No significant differences were found between the clozapine and non‐clozapine groups with regard to any of the quality of life domains.

Conclusion

A combination of economical and clinical factors, health policies and the characteristics of the treatment settings plays important roles in determining clozapine use. Clozapine appears to have little significant influence on quality of life in clinical stable Chinese patients with schizophrenia. Copyright © 2007 John Wiley & Sons, Ltd.
CNTO 859, a humanized anti‐tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft models
Authors: Ngo Cam V. , Picha Kristen , McCabe Francis , Millar Hillary , Tawadros Richard , Tam Susan H. , Nakada Marian T. , Anderson G. Mark
Published: December 2006

Thromboembolic complications are frequently associated with advanced cancer. Interestingly, one of the major initiators of blood coagulation, tissue factor (TF), is reported to be overexpressed in several tumor types and can be found on both tumor cells and tumor vasculature. Although the exact mechanisms have yet to be elucidated, TF expressed on tumor cells can trigger intracellular signaling events through various pathways that can lead to tumor angiogenesis, proliferation, and metastasis. There exists preclinical evidence that disruption of TF dependent signaling can effectively inhibit tumor cell migration, metastasis, and angiogenesis. Here, we report for the first time that an antibody to tissue factor can also prevent tumor growth in vivo. Prophylactic administration of CNTO 859, a humanized anti‐human TF antibody, was shown to inhibit experimental lung metastasis of MDA‐MB‐231 human breast carcinoma cells by over 99% compared to a control antibody. Furthermore, therapeutic doses of CNTO 859 were shown to reduce tumor incidence and growth of orthotopically implanted MDA‐MB‐231 cells. © 2006 Wiley‐Liss, Inc.
Excess of cancers in Europe: A study of eleven major cancers amenable to lifestyle change
Authors: Soerjomataram Isabelle , de Vries Esther , Pukkala Eero , Coebergh Jan Willem
Published: December 2006

Worldwide an estimated 11 million cancer cases were diagnosed in 2002, one quarter being in Europe. We estimated the potential in avoidable numbers and proportions of 11 cancers amenable to prevention (cancers of the oral cavity, oesophagus, stomach, colorectal, pancreas, laryngeal, lung, female breast, endometrium, kidney and bladder) in 28 European countries. We assumed that the aggregated rate of 3 countries with lowest incidence to be attainable throughout Europe. The difference between the age‐ and gender‐specific national cancer incidence rates and the lowest rate observed in 2002 was determined and defined as “avoidable.” Of the 1.4 million adult cases of selected cancers and countries within our study, 363,000 (59%) cancers in males and 326,000 (45%) cancers in females were hypothetically avoidable. Among men, the proportion was largest in Hungary (77%) and among women, in Belgium (54%). Assuming that differences in cancer incidence are not attributable to genetic susceptibility or diagnostic activity, about 50% of all cases of these 11 cancers could be potentially avoided, especially by decreased smoking among men. Interventions directed at reducing smoking, obesity and alcohol use as well as increasing physical activity and fruit and vegetable intake are necessary to attain lower incidence rates. It is important to recognize that the actual preventable cancer by eliminating currently known risk factors is somewhat less than we have estimated. © 2006 Wiley‐Liss, Inc.
Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration
Authors: Chen Yian , Zheng Bin , Robbins David H. , Lewin David N. , Mikhitarian Kaidi , Graham Amanda , Rumpp Laurrie , Glenn Tammy , Gillanders William E. , Cole David J. , Lu Xinghua , Hoffman Brenda J. , Mitas Michael
Published: December 2006

To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound‐guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real‐time RT‐PCR in a training set of tissues in which the final diagnosis was PDAC (n = 20) or CP (n = 10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value = 0.895, 95% CI = 0.728–0.976). In the set of test tissues (n = 14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6‐gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6‐gene classifier were “undefined,” the accuracy of the UPAR/6‐gene classifier was 100% in training samples (n = 29), 92% in 12 test samples (p = 0.004 that results were randomly generated; p = 0.046 that the UPAR/6‐gene classifier was comparable to UPAR alone; χ2 test), 100% in 3 samples for which the initial cytological diagnosis was “suspicious” and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis. © 2006 Wiley‐Liss, Inc.
Parity, tubal sterilization, hysterectomy and risk of primary fallopian tube carcinoma in Finland, 1975–2004
Authors: Riska Annika , Sund Reijo , Pukkala Eero , Gissler Mika , Leminen Arto
Published: December 2006

We studied the possible relationship among parity, female sterilization, hysterectomy and the risk of primary fallopian tube carcinoma (PFTC) in a case–control study in Finland in cases occurring between 1975 and 2004. A total of 573 PFTC cases were identified from the Finnish Cancer Registry, and10 age‐matched controls per case were randomly selected from the Finnish Central Population Registry. In multivariate analysis (including 189 PFTC cases and 1764 controls) parity was protective: the odds ratio (OR) for 1–2 deliveries was 0.63 (95% CI 0.44–0.91) and for ≥3 deliveries, 0.32 (95% CI 0.19–0.52). The OR for sterilization was 0.74 (95% CI 0.42–1.30) and for hysterectomy 1.27 (95% CI 0.73–2.21). Our findings suggest a possible hormonal background as regards the development of PFTC. © 2006 Wiley‐Liss, Inc.