bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorinated β‐Diketones for the Extraction of Lanthanide Ions: Photophysical Properties and Hydration Numbers of Their EuIII Complexes
Authors: Chauvin Anne‐Sophie , Gumy Frédéric , Matsubayashi Izuru , Hasegawa Yuko , Bünzli Jean‐Claude G.
Published: December 2005

Tris(β‐diketonato)europium(III) with a series of variably fluorinated ligands derived from 3,5‐heptanedione were synthesised with the aim of determining their hydration state under extraction conditions. The number of coordinated water molecules was determined by measuring the lifetime of the Eu(5D0) excited level in water and deuterated water. The hydration gain (Δq = q – q0) after shaking chloroform solutions during 10 min with 0.1 M NaClO4 aqueous solutions depends on the fluorination extent of the diketonates: fluorination of one methyl group leads to a decrease in Δq of ca. 0.5 unit, while fluorination of one ethyl group results in a decrease of ca. 1.3 units. Highly fluorinated complexes (i.e with hexafluoroacetylacetonate and related ligands) display a hydration number close to one while poorly fluorinated compounds (or nonfluorinated ones, such as the acetylacetonate complex) have a hydration state close to two. Photophysical properties of the EuIII β‐diketonates are also described and the synthesis of the fluorinated β‐diketones is re‐investigated and discussed in details. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis of Amino‐ and Bis(bromomethyl)‐Substitued Bi‐ and TetradentateN‐Heteroaromatic Ligands: Building Blocks for Pyrazino‐Functionalized Fullerene Dyads
Authors: Kleineweischede Andreas , Mattay Jochen
Published: December 2005

In this paper we describe the synthesis of amino‐ and bis(bromomethyl)‐substituted derivatives of phenanthroline (phen), pyrazino[2,3‐f]‐phenanthroline (pphen), dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz), pyrazino[2,3‐i]dipyrido[3,2‐a:2′,3′‐c]phenazine, 2,3‐bis(2‐pyridyl)pyrazine (dpp), 2,3‐bis(2‐pyridyl)quinoxaline (dpq) and 7,8‐bis(2‐pyridyl)pyrazino[2,3‐g]quinoxaline. These substituted bi‐ and tetradentate N‐heteroaromatic ligands are potential synthons for the preparation of the fullerene ligands 4–9. The diketones, 1,10‐phenanthroline‐5,6‐dione 11a (phendione), 2,2‐pyridyl 11b and 1,4‐dibromo‐2,3‐butanedione 33 were used as starting materials. Phendione was converted into the phendiamine 13 by a two‐step synthesis via the dioxime of the diketone 11a. Amino‐substituted dppz and dpq derivatives were obtained by the reduction of the corresponding nitro compounds that were obtained by the Schiff base condensation of the diketones 11a and 11b and the appropriate o‐phenylenediamine derivatives. An alternative synthetic route to the diamines 20a and 20b by detosylation of the diamino‐substituted dppzand dpq ligands is also presented. Synthesis of the bis(bromomethyl)‐substituted pphen, dpp, dppz and dpq derivatives was performed by the photochemical addition of bromine. Alternatively, synthesis of the bis(bromomethyl)‐substituted pphen, pdppz and pdpq is also possible by the condensation of 1,4‐dibromo‐2,3‐butanedione 33 and phendiamine or the diamino‐substituted dppz and dpq derivatives. The latter two compounds can be also prepared by the condensation of diketones 11a and 11b with 6,7‐diamino‐2,3‐bis(bromomethyl)quinoxaline. Although the synthesis of some dppz and dpq ligands is already published, we herein present improved or alternative synthetic strategies leading to higher yields and/or higher purity of these N‐heteroaromatic ligands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Linking the 3′ Ends of Oligonucleotide Duplexes with Cystine Disulfide Bridges
Authors: Marchán Vicente , Pulido Daniel , Pedroso Enrique , Grandas Anna
Published: December 2005

Oligonucleotide duplexes with cystine disulfide 3′‐3′ interstrand cross‐links were synthesized. Stepwise solid‐phase procedures, followed by basic deprotection under controlled conditions and air oxidation, afforded various disulfide‐linked duplexes differing in the peptide and oligonucleotide composition and length. Some of these nucleopeptides form unimolecular duplexes in which peptide–minor‐groove interactions are established, while others may give rise to extended nanostructures. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis and Antiviral Evaluation of Carbocyclic 3′‐Azidothymidine (AZT) Analogues and Their cycloSal‐Phosphate Triesters
Authors: Ludek Olaf R. , Balzarini Jan , Meier Chris
Published: December 2005

Carbocyclic analogues of the anti‐HIV dideoxynucleoside 3′‐azido‐3′‐deoxythymidine AZT (1) were synthesized. Starting from the enantiomerically pure carbocyclic 2′‐deoxythymidine 2, four different carbocyclic AZT analogues 2,4–6 were prepared. Moreover, the nucleoside analogues were converted into their membrane‐permeable cycloSal‐phosphate triesters. All compounds were tested in vitro for their anti‐HIV activity in human T‐lymphocytes (CEM/0). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Determination of different classes of amines with capillary zone electrophoresis and contactless conductivity detection
Authors: Gong Xiao Yang , Hauser Peter C.
Published: December 2005

The use of contactless conductivity detection for the determination of different organic amines in CE was successfully demonstrated. Aliphatic nonUV‐absorbing species could be determined along absorbing compounds by measuring the conductivity of their protonated forms. The species tested included short‐chained aliphatic primary, secondary and tertiary amines, branched aliphatic amines, diamines, hydroxyl‐substituted amines as well as species incorporating aromatic and nonaromatic cyclic moieties. Highest sensitivity was obtained with BGE solutions containing solely acetic acid. A concentration of 0.5 M at a pH value of 2.5 was used. Detection limits were in the order of 1 μM. Complete separation of cis‐ and trans‐1,2‐diaminocyclohexane could be achieved by adding 18‐crown‐6 as modifier to the electrolyte solution.
A new multiphasic buffer system for benzyldimethyl‐n‐hexadecylammonium chloride polyacrylamide gel electrophoresis of proteins providing efficient stacking
Authors: Kramer Michael L.
Published: December 2005

Acidic PAGE systems using cationic detergents such as benzyldimethyl‐n‐hexadecylammonium chloride (16‐BAC) or CTAB have proven useful for the detection of methoxy esters sensitive to alkaline pH, resolving basic proteins such as histones and membrane proteins. However, the interesting phosphate‐based system suffered from poor stacking, resulting in broadened bands and long running times. Therefore, a new 16‐BAC PAGE system based on the theory of moving boundary electrophoresis with properties comparable to the classical SDS‐PAGE system was designed. As a result a new multiphasic analytical 16‐BAC PAGE system providing efficient stacking and significantly shorter running times is presented here. It is based on acetic acid and methoxyacetic acid as common ion constituents. This PAGE system takes advantage of the additional counterstacking effect due to a cross boundary electrophoresis system resulting from the selected buffer constituents. Furthermore, the concentration of 16‐BAC was optimized by determining its previously unknown CMC. Due to efficient focusing of the introduced tracking dye, methyl green, termination of electrophoresis can now be more easily followed as compared to the Schlieren line.
Enhanced spontaneous metastasis in bikunin‐deficient mice
Authors: Yagyu Tatsuo , Kobayashi Hiroshi , Matsuzaki Hidenori , Wakahara Kiyoshi , Kondo Toshiharu , Kurita Noriyuki , Sekino Hideo , Inagaki Kiyokazu
Published: December 2005

Previously, we showed that bikunin, a Kunitz‐type protease inhibitor, inhibits invasion and metastasis in several types of cancer cells possibly through suppression of upregulation of urokinase‐type plasminogen activator (uPA) expression. Bikunin corresponds to a light chain of the inter‐alpha inhibitor. To explore critical role of endogenous bikunin, we used bikunin knockout (Bik−/−) mice. Here, we show that 1) higher frequency of spontaneous 3LL lung metastasis was observed in Bik−/− mice compared to Bik+/+ mice, suggesting that bikunin deficiency increases the sensitivity of mice to lung metastasis; 2) administration of exogenous bikunin caused a significant reduction of lung metastasis in Bik−/− and Bik+/+ mice; 3) primary and metastatic tumors significantly upregulated uPA and PAI‐1 expression in Bik−/− mice relative to Bik+/+ mice at least through phosphorylation of ERK1/2 and 4) exogenous bikunin suppressed phosphorylation of ERK1/2 and upregulation of uPA and PAI‐1 expression in 3LL cells in response to G‐CSF. These data allow us to conclude that the increased sensitivity of Bik−/− mice to lung metastasis in vivo is due to a lack of circulating proteins of the inter‐alpha inhibitor family, especially bikunin. © 2005 Wiley‐Liss, Inc.
Diet and body mass, and oral and oropharyngeal squamous cell carcinomas: Analysis from the IARC multinational case–control study
Authors: Kreimer Aimée R. , Randi Giorgia , Herrero Rolando , Castellsagué Xavier , Vecchia Carlo La , Franceschi Silvia
Published: December 2005

Tobacco and alcohol use are the main risk factors for oral and oropharyngeal cancers, yet, dietary habits may also be of importance. Data from a series of case–control studies conducted in 9 countries worldwide (1,670 cases and 1,732 controls) were used to investigate the role of several food groups and body mass index (BMI). Low BMI significantly increased the odds ratio (OR) of cancer more than 2‐fold among ever‐ and never‐tobacco users and ever‐ and never‐alcohol drinkers. After adjustment for potential confounders, high intake of fruits and vegetables significantly reduced the OR of cancer compared to low intake among ever‐tobacco users (OR 0.4, 95% confidence interval [CI] 0.3–0.6), although not among never‐tobacco users (OR 1.1, 95% CI 0.6–2.0). Similarly, the protective effect of high fruit and vegetable consumption was present among ever‐drinkers (OR 0.4, 95% CI 0.3–0.6), but not among never‐drinkers (OR 1.0, 95% CI 0.6–1.6). In conclusion, low BMI increases the risk of oral cancer, and vegetables and fruits may modulate the carcinogenic effects of tobacco and alcohol. © 2005 Wiley‐Liss, Inc.
Multilocus inheritance determines predisposition to α‐radiation induced bone tumourigenesis in mice
Authors: Rosemann Michael , Kuosaite Virginija , Kremer Markus , Favor Jack , Quintanilla‐Martinez Leticia , Atkinson Michael J.
Published: December 2005

In a recent study, we presented evidence for genetic predisposition governing radiation osteosarcomagenesis in mice. Following the incorporation of the bone‐seeking α emitter 227Th, ˜25% of the variance in osteosarcoma incidence was determined by inherited genetic factors. We have now mapped 5 susceptibility loci in crosses between the more susceptible BALB/c and the more resistant CBA/Ca strains. The major QTL on chromosome 14 overlaps with a locus that was already found in our previous study, using different strains of mice. Here, we investigate the effect by which the major susceptibility locus and 4 minor modifier loci interact to influence osteosarcoma predisposition. Following incorporation of the bone‐seeking isotope, 100% of mice that harbour high‐risk genotypes at all 5 susceptibility loci develop osteosarcoma with an average of 472 days latency times. In 10 mice inheriting exclusively low‐risk genotypes only 1 osteosarcoma was found, arising after 733 days latency time. Inheritance of distinct combinations of BALB/c and CBA/Ca alleles at the susceptibility loci confer more extreme phenotypes in terms of susceptibility or resistance than observed in either of the two parental inbred strains. From the present study, we demonstrate that additive effects of multiple alleles, each making only a minor phenotypic contribution, can combine and significantly alter tumour risk. This mechanism can be of particular importance in genetically heterogeneous populations such as man. © 2005 Wiley‐Liss, Inc.
Prevention of mouse lung tumors by targretin
Authors: Pereira Michael A. , Kramer Paula M. , Nines Ronald , Liu Yue , Alyaqoub Fadel S. , Gunning William T. , Steele Vernon E. , Lubet Ronald A.
Published: December 2005

Targretin has indicated chemotherapeutic activity against nonsmall‐cell lung cancer and chemoprevention in rat mammary gland. Therefore, targretin was evaluated for the prevention of 4‐(methylnitrosoamino)‐1‐(3‐pyridyl)‐1‐butanol (NNK) and vinyl carbamate‐induced lung tumors in female strain A mice. Three experiments were performed: (i) a dose‐response study with vinyl carbamate‐induced tumors; (ii) a limited treatment study also with vinyl carbamate and (iii) prevention of NNK‐induced tumors. In the dose‐response study, 0, 10, 30, 100 and 300 mg/kg targretin were administered after vinyl carbamate. Dose levels of 30 mg/kg and greater significantly decreased tumor multiplicity by >19%. However, the efficacy of 30 and 300 mg/kg was not significantly different demonstrating a shallow dose‐response relationship. In the limited treatment study, 200 mg/kg targretin was administered to the mice from 4–13, 4–19, 4–25 and 23–25 weeks after vinyl carbamate. Administering targretin from weeks 4–19 and 4–25 decreased the multiplicity of tumors from 35.3 ± 1.43 to 29.1 ± 1.51 and 25.0 ± 0.93, respectively, and along with administering it from weeks 23–25 decreased tumor size. In the third study, when targretin (100 and 300 mg/kg) was administered for 3 weeks after NNK followed by a 20 weeks holding period, tumor multiplicity was reduced from 10.6 ± 1.13 to 6.38 ± 0.75 and 4.60 ± 0.70, respectively. Hence, targretin demonstrated both preventive and therapeutic activity with respect to mouse lung tumors supporting its further development as a preventive and therapeutic agent for lung cancer. © 2005 Wiley‐Liss, Inc.
Combination therapy with 2‐difluoromethylornithine and a polyamine transport inhibitor against murine squamous cell carcinoma
Authors: Chen Yan , Weeks Reitha S. , Burns Mark R. , Boorman David W. , Klein‐Szanto Andres , O'Brien Thomas G.
Published: December 2005

Using a recently developed autochthonous mouse model of squamous cell carcinoma (SCC), a combination therapy targeting polyamine metabolism was evaluated. The therapy combined 2‐difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and MQT 1426, a polyamine transport inhibitor. In 1 trial lasting 4 weeks, combination therapy with 0.5% DFMO (orally, in the drinking water) and MQT 1426 (50 mg/kg i.p., bid) was significantly more effective than with either single agent alone when complete tumor response was the endpoint. In the combination group, 72% of SCCs responded completely vs. 21 and 0% for DFMO and MQT 1426, respectively. A second trial involved a 4‐week treatment period followed by 6 weeks off‐treatment. With apparent cures as an endpoint, combination therapy was again more effective than either agent alone: a 50% apparent cure rate was observed in the combination group vs. 7.7% in the DFMO group. MQT 1426 had no inhibitory effect on SCC ODC activity nor did it enhance the inhibition by DFMO, but SCC polyamine levels declined more rapidly when treated with combination therapy vs. DFMO alone. The apoptotic index in SCCs was transiently increased by combination therapy but not by DFMO alone. Thus, targeting both polyamine biosynthesis and polyamine transport from the tumor microenvironment enhances the efficacy of polyamine‐based therapy in this mouse model of SCC. © 2005 Wiley‐Liss, Inc.
Identification of three major DNA adducts formed by the carcinogenic air pollutant 3‐nitrobenzanthrone in rat lung at the C8 and N2 position of guanine and at the N6 position of adenine
Authors: Arlt Volker M. , Schmeiser Heinz H. , Osborne Martin R. , Kawanishi Masanobu , Kanno Takaharu , Yagi Takashi , Phillips David H. , Takamura‐Enya Takeji
Published: December 2005

3‐Nitrobenzanthrone (3‐NBA) is a potent mutagen and potential human carcinogen identified in diesel exhaust and ambient air particulate matter. Previously, we detected the formation of 3‐NBA‐derived DNA adducts in rodent tissues by 32P‐postlabeling, all of which are derived from reductive metabolites of 3‐NBA bound to purine bases, but structural identification of these adducts has not yet been reported. We have now prepared 3‐NBA‐derived DNA adduct standards for 32P‐postlabeling by reacting N‐acetoxy‐3‐aminobenzanthrone (N‐Aco‐ABA) with purine nucleotides. Three deoxyguanosine (dG) adducts have been characterised as N‐(2′‐deoxyguanosin‐8‐yl)‐3‐aminobenzanthrone‐3′‐phosphate (dG3′p‐C8‐N‐ABA), 2‐(2′‐deoxyguanosin‐N2‐yl)‐3‐aminobenzanthrone‐3′‐phosphate (dG3′p‐N2‐ABA) and 2‐(2′‐deoxyguanosin‐8‐yl)‐3‐aminobenzanthrone‐3′‐phosphate (dG3′p‐C8‐C2‐ABA), and a deoxyadenosine (dA) adduct was characterised as 2‐(2′‐deoxyadenosin‐N6‐yl)‐3‐aminobenzanthrone‐3′‐phosphate (dA3′p‐N6‐ABA). 3‐NBA‐derived DNA adducts formed experimentally in vivo and in vitro were compared with the chemically synthesised adducts. The major 3‐NBA‐derived DNA adduct formed in rat lung cochromatographed with dG3′p‐N2‐ABA in two independent systems (thin layer and high‐performance liquid chromatography). This is also the major adduct formed in tissue of rats or mice treated with 3‐aminobenzanthrone (3‐ABA), the major human metabolite of 3‐NBA. Similarly, dG3′p‐C8‐N‐ABA and dA3′p‐N6‐ABA cochromatographed with two other adducts formed in various organs of rats or mice treated either with 3‐NBA or 3‐ABA, whereas dG3′p‐C8‐C2‐ABA did not cochromatograph with any of the adducts found in vivo. Utilizing different enzymatic systems in vitro, including human hepatic microsomes and cytosols, and purified and recombinant enzymes, we found that a variety of enzymes [NAD(P)H:quinone oxidoreductase, xanthine oxidase, NADPH:cytochrome P450 oxidoreductase, cytochrome P450s 1A1 and 1A2, N,O‐acetyltransferases 1 and 2, sulfotransferases 1A1 and 1A2, and myeloperoxidase] are able to catalyse the formation of 2‐(2′‐deoxyguanosin‐N2‐yl)‐3‐aminobenzanthrone, N‐(2′‐deoxyguanosin‐8‐yl)‐3‐aminobenzanthrone and 2‐(2′‐deoxyadenosin‐N6‐yl)‐3‐aminobenzanthrone in DNA, after incubation with 3‐NBA and/or 3‐ABA. © 2005 Wiley‐Liss, Inc.
Different angiogenic phenotypes in primary and secondary glioblastomas
Authors: Karcher Sibylle , Steiner Hans‐Herbert , Ahmadi Rezvan , Zoubaa Saida , Vasvari Gergely , Bauer Harry , Unterberg Andreas , Herold‐Mende Christel
Published: December 2005

Primary and secondary glioblastomas (pGBM, sGBM) are supposed to evolve through different genetic pathways, including EGF receptor and PDGF and its receptor and thus genes that are involved in tumor‐induced angiogenesis. However, whether other angiogenic cytokines are also differentially expressed in these glioblastoma subtypes is not known so far, but this knowledge might be important to optimize an antiangiogenic therapy. Therefore, we studied the expression of several angiogenic cytokines, including VEGF‐A, HGF, bFGF, PDGF‐AB, PDGF‐BB, G‐CSF and GM‐CSF in pGBMs and sGBMs as well as in gliomas WHO III, the precursor lesions of sGBMs. In tumor tissues, expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 30 tissue‐corresponding glioma cultures revealed a predominant expression of VEGF‐A in pGBMs and significantly higher expression levels of PDGF‐AB in sGBMs. HGF and bFGF were determined in nearly all tumor cultures but with no GBM subtype or malignancy‐related differences. Interestingly, GM‐CSF and especially G‐CSF were produced less frequently by tumor cells. However, GM‐CSF secretion occurred together with an increased number of simultaneously secreted cytokines and correlated with a worse patient prognosis and may thus represent a more aggressive angiogenic phenotype. Finally, we confirmed an independent contribution of each tumor‐derived cytokine analyzed to tumor‐induced vascularization. Our data indicate that an optimal antiangiogenic therapy may require targeting of multiple angiogenic pathways that seem to differ markedly in pGBMs and sGBMs. © 2005 Wiley‐Liss, Inc.
Development in incidence of breast cancer in non‐screened danish women, 1973–2002—a population‐based study
Authors: Fuglede Niels , Langballe Oline , Svendsen Anne Louise , Tjønneland Anne , Dalton Susanne O , Johansen Christoffer
Published: December 2005

The authors report on the incidence rates of breast cancer overall and by histology in a population of unscreened women constituting ∼80% of the total population of women in Denmark from 1973–2002, utilizing the files of the nationwide Danish Cancer Registry. The age‐specific incidence rates of breast cancer increased throughout the period, and further, marked changes in the age‐specific incidence pattern were observed, where the plateau and change of slope around the age of 46–48 in 1973–1981 shifted to around age 64–66 years in 1994–2002. Age‐period‐cohort modeling indicated that these changes were not attributable to a birth cohort effect. Although lobular breast cancer incidence increased more than ductal breast cancer incidence, this was only observed in the first decade after the introduction of the ICD‐O system in Denmark and probably is attributable to this, whereas we observed no disproportionate changes by histology in any age group from 1988–2002. Thus, previous reports of a disproportionate increase in lobular breast cancer could not be confirmed in a non‐screened population, whereas important changes over the past decade in the age‐specific incidence pattern of breast cancer particular around the time of menopause were indicated. © 2005 Wiley‐Liss, Inc.
TRAIL‐induced cell death cooperates with IFN‐γ activation in the graft‐versus‐tumor effect against colon tumors
Authors: Tateishi Keisuke , Ohta Miki , Guleng Bayasi , Kanai Fumihiko , Tanaka Yasuo , Asaoka Yoshinari , Jazag Amarsanaa , Imamura Jun , Imamura Takaaki , Ijichi Hideaki , Ikenoue Tsuneo , Kawakami Takayuki , Fukushima Yasushi , Washida Miwa , Sata Masataka , Miyagishi Makoto , Taira Kazunari , Yoshida Haruhiko , Kawabe Takao , Omata Masao
Published: December 2005

The graft‐versus‐tumor (GVT) effect that occurs following allogeneic bone marrow transplantation (BMT) and donor lymphocyte infusion (DLI) is currently being subjected to intensive investigation because of clinical evidence for GVT efficacy against leukemia. In this report, we investigate the efficacy and molecular mechanisms of GVT against solid tumors, using a modification of the mouse parent‐to‐F1 BMT model. Mouse Colon26 cells in which tumor necrosis factor related apoptosis‐inducing ligand (TRAIL) receptor expression was stably knocked down were transplanted to investigate the role of the TRAIL‐TRAIL receptor system in the GVT effect. In addition, Fas ligand‐(FasL) deficient mice on a C57BL6 (B6) background were used as donors, to determine the significance of the Fas‐FasL system for the antitumor effect. The group that received B6 DLI followed by preconditioning with 950 rad irradiation underwent tumor reduction associated with the induction of IFN‐γ, TRAIL and tumor‐cell apoptosis. In vitro cultured Colon26 cells were resistant to TRAIL but susceptible to the combination of IFN‐γ and TRAIL in a TRAIL‐dose‐dependent manner. The infusion of lymphocytes from FasL‐defective donors reduced the tumor progression, although efficacy was decreased in the TRAIL receptor knockdown tumors but not in wild‐type ones, compared with infusion of B6‐derived lymphocytes. The findings indicate that GVT activity against subcutaneous colon tumors is efficiently induced by preconditioning with irradiation and allogeneic DLI, and that TRAIL and IFN‐γ act cooperatively in the antitumor effect. © 2005 Wiley‐Liss, Inc.
Enhanced bone formation by transforming growth factor‐β1‐releasing collagen/chitosan microgranules
Authors: Lee Jue‐Yeon , Kim Kyoung‐Hwa , Shin Seung‐Yoon , Rhyu In‐Chul , Lee Yong‐Moo , Park Yoon‐Jeong , Chung Chong‐Pyoung , Lee Seung‐Jin
Published: December 2005

Collagen/chitosan composite microgranules were fabricated as bone substitutes for the purpose of obtaining high bone‐forming efficacy. The microgranules have the flexibility to fill various types of defect sites with closer packing. The interconnected pores formed spaces between the microgranules, which allowed new bone ingrowth and vascularization. In addition, the transforming growth factor‐beta 1 (TGF‐β1) was incorporated into the microgranules in order to improve bone‐healing efficacy. The collagen/chitosan microgranules were fabricated by dropping a mixed solution into a NaOH/ethanol solution. TGF‐β1 was loaded into the collagen/chitosan microgranules by soaking the microgranules in a TGF‐β1 solution. Scanning electron microscopy (SEM) observations and experiments examining the release of TGF‐β1 from chitosan and the collagen/chitosan microgranules were performed. SEM was used to examine the cell morphologies on the microgranules and cell proliferation was evaluated using a dimethylthiazole tetrazolium bromide assay. The differentiated cell function was assessed by measuring the alkaline phosphatase (ALPase) activity as well as detecting an osteocalcin assay. The in vivo bone‐regeneration experiments were performed using a rabbit calvarial defect model. TGF‐β1 was released from the collagen/chitosan microgranules at a therapeutic concentration for 4 weeks. SEM indicated that the seeded osteoblastic cells were firmly attached to the microgranules and proliferated in a multilayer manner. The proliferation of the osteoblasts on the TGF‐β1‐loaded microgranules was the highest among the different types of microgranules tested. The ALPase activity and osteocalcin level of all the samples increased during the culture period, and the TGF‐β1‐loaded microgranules had a significantly higher ALPase activity and osteocalcin content than the other microgranules. The TGF‐β1‐loaded microgranules demonstrated a higher bone‐regenerative capacity in the rabbit calvarial defects after 4 weeks than the TGF‐β1‐unloaded microgranules. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
A physically meaningful method for the comparison of potential energy functions
Authors: Alonso José Luis , Echenique Pablo
Published: December 2005

In the study of the conformational behavior of complex systems, such as proteins, several related statistical measures are commonly used to compare two different potential energy functions. Among them, the Pearson's correlation coefficient r has no units and allows only semiquantitative statements to be made. Those that do have units of energy and whose value may be compared to a physically relevant scale, such as the root‐mean‐square deviation (RMSD), the mean error of the energies (ER), the standard deviation of the error (SDER) or the mean absolute error (AER), overestimate the distance between potentials. Moreover, their precise statistical meaning is far from clear. In this article, a new measure of the distance between potential energy functions is defined that overcomes the aforementioned difficulties. In addition, its precise physical meaning is discussed, the important issue of its additivity is investigated, and some possible applications are proposed. Finally, two of these applications are illustrated with practical examples: the study of the van der Waals energy, as implemented in CHARMM, in the Trp‐Cage protein (PDB code 1L2Y) and the comparison of different levels of the theory in the ab initio study of the Ramachandran map of the model peptide HCO‐L‐Ala‐NH2. © 2005 Wiley Periodicals, Inc. J Comput Chem 27: 238–252, 2006
Identification of basolateral membrane targeting signal of human sodium‐dependent dicarboxylate transporter 3
Authors: Bai Xueyuan , Chen Xiangmei , Feng Zhe , Hou Kai , Zhang Ping , Fu Bo , Shi Suozhu
Published: December 2005

Sodium‐dependent dicarboxylate transporters (NaDC) include low‐affinity NaDC1 and high‐affinity NaDC3. Despite high similarities structurally and functionally, both are localized to opposite surfaces of renal tubular cells. The molecular mechanisms and localization signals leading to this polarized distribution remain unknown. In this study, distribution of NaDC3 in human kidney tissue was firstly observed by immunohistochemistry and immunofluorescence. Then, EGFP‐fused wild‐type, NH2‐ and COOH‐terminal deletion and point mutants of NaDC3, and chimera between NaDC3 and NaDC1, were generated and transfected into polarized renal cells lines, LLC‐PK1 and MDCK. Their subcellular localizations were analyzed by laser confocal microscopy. Immunolocalization results revealed that NaDC3 was expressed at basolateral membrane of human renal proximal tubular epithelia. Confocal examinations showed that wild‐type NaDC3 was targeted to the basolateral membrane of MDCK and LLC‐PK1. Deletion mutations indicated that the basolateral targeting signal of NaDC3 located within a short sequence AKKVWSARR of its amino‐terminal cytoplasmic domain. Addition of this sequence could redirect apical NaDC1 to the basolateral membrane of LLC‐PK1. Point mutagenesis revealed that mutation of either of two hydrophobic amino acids V and W in this short sequence largely redirected NaDC3 to both apical and basolateral surfaces of LLC‐PK, indicating that the two hydrophobic amino acids are critical for the basolateral targeting of NaDC3. Our studies provide direct evidence of the localization of NaDC3 at the basolateral membrane of human renal proximal tubule cells and identify a di‐hydrophobic amino acid motif VW as basolateral localization signal in the N‐terminal cytoplasmic domain of NaDC3. J.Cell.Physiol. © 2005 Wiley‐Liss, Inc.
Fiducial markers for MR histological correlation in ex vivo or short‐term in vivo animal experiments: A screening study
Authors: Rouvière Olivier , Reynolds Carol , Le Yuan , Lai Jinping , Roberts Lewis R. , Felmlee Joel P. , Ehman Richard L.
Published: December 2005

Purpose

To test injectable fiducial markers for magnetic resonance (MR) histological correlation in ex vivo or in vivo animal experiments.

Materials and Methods

A total of 35 potential markers were tested ex vivo in pork muscle. The end‐points were: 1) visibility, size, and shape on MR images and at macroscopic examination; 2) 24‐hour stability; and 3) microscopic appearance. Selected markers were injected in vivo (rabbit's muscle and breast tumor tissue) to test their three‐hour in vivo stability and their potential toxicity. Finally, different dilutions of the two best markers were assessed again through the same screening tests to determine whether their size on MR images could be customized by dilution.

Results

Two fluid acrylic paints containing inorganic pigments were found to be potentially interesting markers. On MR images, they created well‐defined susceptibility artifacts. The markers made with iridescent bronze paint (iron oxide coated mica particles) were readily visible on microscopy and their size on MR images could be customized by dilution. The iridescent stainless steel paint (iron, chromium, nickel) created ex vivo the smallest markers in tissue but needed colloidal iron staining to be visible on microscopy and could not be easily diluted.

Conclusion

Fluid acrylic paints are potentially interesting markers for MR histological correlation. Further studies are needed to assess their long‐term properties. J. Magn. Reson. Imaging 2006. © 2005 Wiley‐Liss, Inc.
MR histological correlation: A method for cutting specimens along the imaging plane in animal or ex vivo experiments
Authors: Rouvière Olivier , Reynolds Carol , Hulshizer Thomas , Rossman Phillip , Le Yuan , Felmlee Joel P. , Ehman Richard L.
Published: December 2005

Purpose

To assess a method aimed at cutting histological specimens along the magnetic resonance (MR) imaging plane.

Material and Methods

The method is performed in two steps: the imaging plane (defined by three acrylic paint markers) is made horizontal under MR guidance by using a mobile platform that can be rotated in three directions (PlaneFinder device [PFD]); then, the specimen is embedded in wax and cut horizontally. Three‐dimensional images parallel to the markers' plane were obtained on 31 pork muscles containing a central hole with a pyramidal shape, with a technique of reference (RT images) and with PFD (PF images), before and after fixation. The last 17 fixed specimens were cut in the markers' plane (tissue section [TS] images). The central hole area (CHA) in the markers' plane was used to compare RT, PF, and TS images. Using a workstation, PF images were rotated and translated to estimate the shift along each direction that could explain the entire CHA difference between RT, PF, and TS images (maximum error, worst‐case scenario).

Results

Excellent correlation was found between RT and PF images (r = 0.989, slope = 1.0175), PF and TS images (r = 0.991, slope = 1.0058), and RT images on fresh specimens and TS images (r = 0.979, slope = 1.0732). For each step, the maximum angle error was ≤ 3° in 88–95% of the specimens.

Conclusion

Our methodology can be used to cut specimens along the imaging plane with high accuracy. J. Magn. Reson. Imaging 2006. © 2005 Wiley‐Liss, Inc.
Multislice, dual‐imaging sequence for increasing the dynamic range of the contrast‐enhanced blood signal and CNR of myocardial enhancement at 3T
Authors: Kim Daniel , Axel Leon
Published: December 2005

Purpose

To develop a multislice, first‐pass perfusion imaging sequence for increasing the effective dynamic range of the contrast‐enhanced blood signal and the contrast‐to‐noise ratio (CNR) of myocardial wall enhancement.

Materials and Methods

A hybrid echo‐planar imaging (EPI) pulse sequence was modified to acquire data for both the arterial input function (AIF) and the myocardium, using two different saturation‐recovery time delays (TDs) and spatial resolutions, after a single saturation pulse. Five healthy subjects were scanned at 3T in three short‐axis levels of the heart per heartbeat during passage of a high‐dose bolus of contrast agent. The T1‐weighted signal‐time curve of the blood was converted to AIF using empirical conversion tables derived from phantom experiments.

Results

In all subjects the calculated AIF was consistently less distorted and higher for the short‐TD protocol than for the long‐TD protocol (peak concentration: 5.0 ± 1.0 mM vs. 3.0 ± 0.6 mM; P < 0.01). A combination of EPI, long TD, high‐dose bolus of contrast agent, and 3T imaging yielded relatively strong peak enhancement in the myocardium (CNR = 11.9 ± 3.3).

Conclusion

Our dual‐imaging approach at 3T seems promising for acquiring both a relatively accurate AIF and a high CNR of myocardial wall enhancement in multiple slices per heartbeat. J. Magn. Reson. Imaging 2006. © 2005 Wiley‐Liss, Inc.
Wine produced by immobilized cells on dried raisin berries in sensory evaluation comparison with commercial products
Authors: Tsakiris Argiris , Kourkoutas Yiannis , Dourtoglou Vassilis G , Koutinas Athanasios A , Psarianos Constantinos , Kanellaki Maria
Published: December 2005

Comparative sensory evaluation of wines produced by immobilized cells of Uvaferme 299 on dried raisin berries and free cells using the Saint Denis grape variety and of commercial Greek products (‘Biblia Chora’ rosé wine produced from the Syrah grape variety, ‘Palivos’ and ‘Strofilia’ rosé wines both produced from the Agiorgitiko grape variety) was carried out. Sensory evaluation was conducted twice by 11 tasters previously trained and a method for panel validation was proposed. Subsequently, the wines were evaluated for their aroma intension, aroma complexity, aroma elegance and overall quality. Duncan's multiple range test clearly showed that there were statistically significant differences between wines produced using different grape varieties and fermentation conditions. Linear regression analysis of the results was performed in order to investigate which sensory parameter had a significant effect on the overall quality and it revealed that only aroma elegance affected significantly the overall quality. Wine produced by immobilized cells scored a statistically higher value for its overall quality than the wine produced by free cells. Finally, discriminant sensory evaluation revealed a gooseberry, cherry, mint aroma for ‘Biblia Chora’ wine and a citrus, rose aroma for ‘Strofilia’ and ‘Palivos’ wines. Wines produced using immobilized and free cells were characterized by a fruity, banana‐like aroma, and a herbaceous note was predominant. Copyright © 2005 Society of Chemical Industry
Application of agglomerative hierarchical clustering to identify consumer tomato preferences: influence of physicochemical and sensory characteristics on consumer response
Authors: Serrano‐Megías Marta , López‐Nicolás Jose Manuel
Published: December 2005

A multiple regression model was developed to predict the acceptability of the four tomato varieties studied (Aranka, Cherry, Beef and Pitenza). Agglomerative hierarchical clustering showed the presence of four consumer clusters. One cluster preferred small tomatoes (Aranka and Cherry) and another cluster the larger tomatoes (Beef and Pitenza). In the sensorial analysis Aranka was the preferred variety, scoring more highly in taste, odour, acidity, sweetness and hardness. In the physicochemical analysis Aranka also obtained the highest values for titratable acidity (TA) and sugars (SSC), confirming that these parameters are important in tomato flavour. Lower values for both sets of parameters were reflected by lower consumer acceptability, with Beef and Pitenza receiving the lowest score for these flavours attributes (except odour). A significant correlation between the sensorial and physicochemical parameters was also observed: odour was positively correlated with calibre, while taste, acidity, hardness and acceptability were negatively correlated with calibre, pH and SSC/TA and positively correlated with SSC and TA. Copyright © 2005 Society of Chemical Industry
In Situ Compatibilization of PS/EPDM Blends during Ultrasonic Extrusion
Authors: Li Jiang , Guo Shaoyun , Slezák Radek , Hausnerová Berenika
Published: December 2005

Summary: In this paper, high power ultrasound was introduced into polystyrene (PS)/ethylene‐propylene diene monomer (EPDM) (80/20) blend melts during extrusion. The structure and properties of PS/EPDM blends treated ultrasonically, such as their mechanical properties, phase morphology, dynamic rheological behavior and the size distribution fractal dimension of dispersed particles, as well as the interfacial tension between the PS and EPDM phases, were studied. The experimental results indicated that ultrasonic treatment could improve the compatibility of PS/EPDM blends. This is attributed to the formation of a copolymer of PS and EPDM by the combination of different macroradicals, resulting from the homolytic cleavage of polymer chains induced by ultrasonic irradiation. The disproportional termination of the macroradicals leads to the degradation of PS and EPDM. Some properties, like mechanical and linear viscoelastic characteristics, were affected by both ultrasonic compatibilization and degradation. These properties depended strongly on the ultrasonic intensity, ultrasonic treatment time and number of extrusions (repeated extruded times).

Differential particle size distribution of the dispersed phase in PS/EPDM blends.

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Differential particle size distribution of the dispersed phase in PS/EPDM blends.
A New Method to Prepare Maleic Anhydride Grafted Poly(propylene)
Authors: Qiu Wulin , Hirotsu Takahiro
Published: December 2005

Summary: A new method to prepare maleic anhydride grafted poly(propylene) (MAPP) was developed successfully. The grafting reaction of maleic anhydride (MA) onto poly(propylene) (PP) was performed with the aid of ball‐milling, and the grafting mechanism was proposed based on the experimental results. MAPP was prepared by ball‐milling of PP powder, MA, and peroxide initiator in balls‐containing jars with a planetary ball mill for a certain time. Factors were considered on reaction time, rotational speed of the mill, cyclic milling mode, kind and concentration of peroxide, and concentration of MA. Results show that MAPP obtained contains the main structures of end‐grafting type (both single and oligomeric) and bridge‐grafting type. Compared with the conventional melt‐mixing method, MAPP obtained through the ball‐milling method reveals alleviated degradation of PP or even increased molecular weight of resultant MAPP. This novel method has also the advantages of lower process temperature and solventless, energy efficient, low cost and simple running process. Furthermore, it is very easy to get purified products.

Key steps for preparing MAPP through ball‐milling.

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Key steps for preparing MAPP through ball‐milling.
The history of the Drug Utilization Research Group in Europe
Authors: Bergman Ulf
Published: December 2005

Following the recommendations from a World Health Organization (WHO)/Euro symposium Consumption of drugs in 1969, a common classification system for drugs was developed, the Anatomical Therapeutic Chemical (ATC), and a technical unit of comparison, the Defined Daily Dose (DDD), as a comparative unit of drug use. This was found to be robust across therapeutic classifications, dosing forms and diverse populations. To maintain and develop the ATC/DDD system a WHO‐Collaborating Centre was established in Oslo. As this was found to be of global interest the centre now reports to the WHO headquarters in Geneva.

An informal WHO Drug Utilization Research Group (WHO‐DURG), later the EuroDURG, has by now met 28 times in Europe. Since 1994 in Stockholm all these meetings have been with ISPE (International Society for Pharmacoepidemiology) when meeting in Europe.

The main focus was initially to improve drug utilization through cross‐national drug utilization studies based on the ATC/DDD methodology as they revealed large differences between and within countries that could not easily be explained by morbidity differences alone. These observed differences have led to the expansion of the area to include social, economic and qualitative methods with a more generalized public health focus. One of the most recent contributions was the development of drug use quality indicators. Copyright © 2005 John Wiley & Sons, Ltd.
Herbal products: behaviors and beliefs among Italian women
Authors: Zaffani Silvana , Cuzzolin Laura , Benoni Giuseppina
Published: December 2005

Purpose

The use of phytotherapy is growing worldwide, but the popular perception is that this kind of approach is natural and therefore safer than traditional medicine; for this reason the use is frequently not communicated to the doctor. Instead, even if many herbal remedies are benign in nature, some of these therapies have potentially harmful side effects or adverse interactions with other medications. So, the purpose of our study was to analyze the behavior patterns and decision‐making modalities about herbal remedy use among a sample of Italian women.

Methods

During a 5‐month period, interviews to women attending the outpatient ambulatory of an urban university general hospital were made on the basis of a pre‐structured 25‐item questionnaire.

Results

Among a random study population of 1044 subsequent patients, 491 women (47.03%) reported to have been taking one or more herbal products in the last year, sometimes used during pregnancy or given to their children (35.23%). The 10 most frequently used herbal products reported were propolis, aloe, valerian root, blueberry, fennel, dandelion, mallow, arnica, thyme, and Echinacea. The major purposes for using these products were to stimulate the immune system and to cure respiratory problems. 47/491 (9.57%) women reported side effects, but only 36% referred to the doctor. In most of the cases, herbal products were taken in combination with drugs (44.61%) or homeopathic treatments (11.81%). The majority of our women did not obtain information about this kind of therapy from a health care provider (72.71%).

Conclusions

The present survey highlights the general use of phytomedicines by a sample of Italian women, the potential risk of their confidence with the ‘natural world,’ and the lack of discussion on this argument with doctors and pharmacists. This suggests the importance of training for health care providers and the need of informational programs for consumers. Copyright © 2005 John Wiley & Sons, Ltd.
Trends in new drug interactions for pharmaceutical products in Japan
Authors: Yoshida Naoko , Yamada Akito , Mimura Yasuhiko , Kawakami Junichi , Adachi Isao
Published: December 2005

Purpose

The aim of the present study was to elucidate the trends in drug interactions for pharmaceutical products in Japan by examining safety profile updates.

Methods

All 12 422 prescription drugs currently on the Japanese market were included in the study. Revisions to their product information (or package insert: PI) were investigated from January 2000 to December 2003. The publication ‘Drug Safety Update,’ which is a summary of the revisions made to the precautions in PIs and is issued by The Society of Japanese Pharmacopoeia and The Federation of Pharmaceutical Manufacturers' Associations of Japan under the supervision of the Ministry of Health, Labour and Welfare (MHLW), was used as a data source. The revised drug interactions were categorized according to measures, mechanisms, and evidence from published references.

Results and Conclusions

The results revealed 426 new interactions, including 75 contraindicative combinations, during the survey period. About 45% and 27% of the new interactions involved metabolic and pharmacological processes, respectively, with metabolic interactions involving cytochrome P450 3A4 being the dominant reason for the revision of PIs. Only 37% of the new interactions cited scientific journals and/or books, and 58% of these references cited were published more than 5 years prior to the date of revision. In conclusion, metabolic interactions were the major reasons for the update of safety information after 2000. Published references should be provided in order to assist with clinical management and avoid the undesirable effects of new drug interactions. Copyright © 2005 John Wiley & Sons, Ltd.
Tailored amphiphilic star‐shaped light‐harvesting copolymers
Authors: Chen Ming , Ghiggino Kenneth P , Thang San H , Wilson Gerard J
Published: December 2005

Amphiphilic star‐shaped light‐harvesting copolymers comprising six diblock arms of styryl coumarin (St‐Coumarin) and N‐isopropylacrylamide (NIPAM) surrounding a ruthenium(II) tris(bipyridyl) energy‐trap core have been synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization. The mechanism of excitation energy transfer (EET) from initially excited St‐Coumarin chromophores to the Ru(II) trap has been investigated and is concluded to occur mainly through a single‐step induced dipole–dipole process. Incorporation of the NIPAM sequences results in enhanced EET efficiencies and confers water solubility to the polymers. The photophysical behavior of the copolymers is reported; marked differences are exhibited in aqueous solution when compared to organic solutions. Copyright © 2005 Society of Chemical Industry
Phosphorus dendritic architectures: polyanionic and polycationic derivatives
Authors: Caminade Anne‐Marie , Turrin Cédric‐Olivier , Laurent Régis , Rebout Cyrille , Majoral Jean‐Pierre
Published: December 2005

The synthesis of phosphorus dendrimers having charges in their structure, either in the interior or as end‐groups, is briefly reviewed. The emphasis is then put on the properties and applications of these compounds in the fields of materials science and biology. In the first case, polyionic dendrimers have been used to elaborate new mesoscopically ordered hybrid materials, nanoporous materials, hydrogels, fibres, nanotubes, microcapsules and vesicles. In the second case, the low cytotoxicity measured for the positively charged dendrimers has indicated their potential as transfection agents, and as anti‐prion agents. Copyright © 2005 Society of Chemical Industry