bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantioselective Glucosylation of (R,S)-1-Phenylethanol by the Cultured Suspension Cells of Higher Plants
Authors: Lee Ym Sook , Ito Diana I , Koya Kazuhiko , Izumi Shunsuke , Hirata Toshifumi
Published: March 2006

(R,S)-1-Phenylethanol and its acetate were transformed into their β-d-glucopyranoside by the cultured suspension cells of Nicotiana tabacum and Catharanthus roseus. The glucosylation with the green N. tabacum cells occurred enantioselectively to give the glucoside of the (S)-alcohol, while the biotransformation with the white N. tabacum cells and C. roseus cells gave preferentially the glucoside of the (R)-alcohol.
Synthesis and Catalysis of Colloidal Dispersions of Pd/Ni Bimetallic Clusters
Authors: Toshima Naoki , Lu Ping
Published: March 2006

Pd/Ni bimetallic clusters have been successfully prepared for the first time by a polyol reduction method, in which a mixed solution of Pd and Ni salts were reduced at high temperature by ethylene glycol. The bimetallic clusters are proved by TEM, XRD and preliminary EXAFS analysis to have an alloy structure. The bimetallic clusters show much higher catalytic activity for hydrogenation of nitrobenzene to aniline under mild conditions than the monometallic Pd or Ni clusters.
The Catalytic Friedel-Crafts Acylation Reaction of Aromatic Compounds with Carboxylic Anhydrides Using Combined Catalyst System of Titanium(IV) Chloride Tris(trifluoromethanesulfonate) and Trifluoromethanesulfonic Acid
Authors: Izumi Jun , Mukaiyama Teruaki
Published: March 2006

Various aromatic ketones are prepared in good to high yields with carboxylic anhydrides using combined catalyst system of TiCl(OTf)3 and TfOH.
Synthesis and Unique Packing Structure by X-Ray Analysis of New Types of Stable Trithioles Bound to Fused Aromatic Systems
Authors: Ogawa Satoshi , Nobuta Susumu , Nakayama Ryoichi , Kawai Yasushi , Niizuma Shigeya , Sato Ryu
Published: March 2006

New types of stable trithioles bounds to fused aromatic systems have been synthesized and one of them, phenanthro[9,10-d][1,2,3]trithiole, has been characterized by X-ray crystallographic analysis, which has a unique helical packing arrangement.
Marked Difference between 1,1,3,3-Tetramethyl-2-oxobutyl and 1,3,3-Trimethyl-2-oxo-cyclopentyl Systems in the Grunwald–Winstein Relationships in Solvolysis
Authors: Takeuchi Ken’ichi , Ohga Yasushi , Ushino Takuhiro
Published: March 2006

The solvolysis rates of 1,1,3,3-tetramethyl-2-oxobutyl methanesulfonate (1) have been reported to give a nicely linear Grunwald–Winstein relation, whereas those of structurally similar 1,3,3-trimethyl-2-oxocyclopentyl methanesulfonate (2) exhibit a scattered plot and well correlated by log(k⁄k0) = (0.57 ± 0.07)NOTs + (0.55 ± 0.05)YOTs + (0.03 ± 0.09). These results indicate the difference in the direction of departure of the leaving group in the transition state.
Sugar-Sensing by Chiral Orientation of Dimeric Boronic-Acid-Appended Porphyrins Which Show Selectivity for Glucose and Xylose
Authors: Arimori Susumu , Takeuchi Masayuki , Shinkai Seiji
Published: March 2006

5,10,15,20-Tetrakis(4-boronylphenyl)porphyrin (1) and 5,10,15,20-tetrakis[N-(2- or 4-boronylphenyl)methyl-pyridinium]porphyrin (o-2 or p-2) formed a 1:1 complex, which gave specific exciton-coupling bands in CD spectroscopy only in the presence of glucose and xylose among monosaccharides. The structural examination established that only these monosaccharides can bridge two porphyrins by covalent-bond formation with boronic acids and twist them asymmetrically.
Facile Determination of Dissolved Species in CO2-Amine-H2O System by NMR Spectroscopy
Authors: Suda Taiichiro , Iwaki Toru , Mimura Tomio
Published: March 2006

In order to clarify the characteristic behavior of dissolved state of CO2 in alkanolamine-H2O system five different kinds of alkanolamines were examined spectroscopically under the following conditions: 40 °C for 30 min to 120 min. NMR analysis indicated the presence of five chemical species such as carbamate ion, free amine, bicarbonate, carbonate, and protonated amine. Based on proton NMR, distribution of the respective species against molar loading of CO2 was successfully evaluated.
Organized Photocycloaddition of 4-Benzoylbenzoate with Unsaturated Carboxylates in Hydrotalcite Clay Interlayers
Authors: Shichi Tetsuya , Takagi Katsuhiko , Sawaki Yasuhiko
Published: March 2006

Photoirradiation of a mixture of 4-benzoylbenzoate (1) and 4-(2-phenylethenyl)benzoate yielded regioselective oxetanes in the presence of hydrotalcite clay. Similar irradiation of a mixture of 1 and cinnamate gave rise to β-truxinate, but not oxetane. The unexpected formation of oxetanes is understood by the favorable distance between C=O and C=C bonds packed in clay interlayers.
Nitric Oxide Trapping Efficiencies of Water-Soluble Iron(III) Complexes with Dithiocarbamate Derivatives
Authors: Fujii Satoshi , Yoshimura Tetsuhiko , Kamada Hitoshi
Published: March 2006

NO trapping efficiencies of three water-soluble iron(III) complexes with dithiocarbamate derivatives (DTC) are investigated by electron paramagnetic resonance spectroscopy. The obtained data show the dependence on the the structure of the substituent of -NRR′ portion of DTC and on the solvent nature in which Fe-DTC complex are dissolved.
Palladium-Catalyzed Coupling Reaction of Salicylaldehydes with Aryl Iodides via Cleavage of the Aldehyde C–H Bond
Authors: Satoh Tetsuya , Itaya Tomoaki , Miura Masahiro , Nomura Masakatsu
Published: March 2006

It has been found that the cross-coupling reaction of salicylaldehydes with aryl iodides smoothly proceeds by using a catalyst system of PdCl2/LiCl in the presence of Na2CO3 as base to give the corresponding 2-aroylphenols in good yields, which appears to involve cleavage of the aldehyde C–H bond.
Synthesis of (+),(−)-Model Compounds and Absolute Configuration of Carthamin; A Red Pigment in the Flower Petals of Safflower
Authors: Sato Shingo , Obara Heitaro , Kumazawa Toshihiro , Onodera Jun-ichi , Furuhata Kimio
Published: March 2006

(+)- and (−)-Model compounds of a carthamin were synthesized. The absolute configuration of carthamin was deduced to be S, S by means of CD spectroscopy and X-ray analysis.
Chiral Discrimination of 1-Phenylethylamine by Diastereomeric Salt Formation with Bile Acids. Crystal Structures of Cholic Acid Salts with (R)- and (S)-1-Phenylethylamine
Authors: Sada Kazuki , Maeda Tomohiro , Miyata Mikiji
Published: March 2006

Chiral discrimination of 1-phenylethylamine (1) by diastereomeric salt formation with bile acids is described. X-ray crystallographic studies of the salts between cholic acid (2a) and (R)-, (S)-, and (RS)-1 reveal that more densely packed (S)-1+2a salt crystallizes preferentially by treatment of 2a from racemic 1.
Variable Coordination Geometries in Manganese(II): Eight-, Seven-, and Six-Coordinate Mn(II) Complexes with Pyridyl-Containing Schiff-Base Ligands
Authors: Mikuriya Masahiro , Hatano Yasushi , Asato Eiji
Published: March 2006

Eight, seven-, and six-coordinate manganese(II) complexes with N,N′-bis(2-pyridinylmethylene)-1,3-diaminopropan-2-ol(HL) and N,N′-bis(2-pyridinylmethylene)-1,3-diaminopropane(L′), [Mn(HL)(NO3)2]·C2H5OH, [Mn(L′)(NO3)2], [Mn(L′)(bipy)(CH3OH)](ClO4)2, [Mn(L′)(phen)](ClO4)2, and [MN2(L)(CH3COO)(phen)2](ClO4)2·H2O, have been isolated and characterized by X-ray crystallography.
Ground State Triplet Cation Diradicals Generated from N,N-Dimethylamino Nitronyl Nitroxide and Its Homologues through One-Electron Oxidation
Authors: Sakurai Hiromi , Kumai Reiji , Izuoka Akira , Sugawara Tadashi
Published: March 2006

N,N-Dimethylamino nitronyl nitroxide (1) and its homologues were prepared. One-electron oxidation of these open-shell donors were fond to afford ground state triplet species based on the ESR spectroscopic measurements. The electronic structure of 1+• is characterized by the presence of the two singly occupied orbitals (SOMO and SOMO′) and can be regarded as a hetero-analogue of trimethylenemethane.
Spontaneous Formation of a Molecular Net Assembly by Using Nucleotide Complementarity
Authors: Takenaka Shigeori , Funatu Yousuke , Kondo Hiroki
Published: March 2006

A mixture of ferrous-bipyridine complexes carrying an adenosine or thymidine 20-mer on the ligand forms a two-dimensional molecular network through hybridization of the complementary oligonucleotides.
Synthesis of New Imidazoanthraquinol Fluorophores and Their Fluorescence and Solid-State Inclusion Properties
Authors: Yoshida Katsuhira , Yamasaki Jun , Tagashira Yoshinao , Watanabe Shigeru
Published: March 2006

Isomeric pairs of new imidazoanthraquinol-type fluorophores have been synthesized by reaction of a imidazoanthraquinone dye with organometallic reagents. One of a pair was found to exhibit an intense fluorescence in solutions and to form clathrate crystals that contained various kinds of solvent molecules as guest species.
Synthesis and Self-Assembly of Porphyrin-linked Fullerene on Gold Surface Using S-Au Linkage
Authors: Akiyama Tsuyoshi , Imahori Hiroshi , Ajawakom Anawat , Sakata Yoshiteru
Published: March 2006

Porphyrin-linked fullerene bearing methylthio group was prepared by 1,3-dipolar cycloadditon of the azomethine ylide, generated in situ using N-methylglycine and a formylporphyrin, with C60. Self-assembled monolayer was formed by soaking Au electrode into a solution of the porphyrin-C60 dyad. The photocurrent was observed for the photochemical cell in the presence of electron carrier under illumination.
Preparation of Calcium-Strontium Apatite through Mechanochemical Method
Authors: Yokogawa Yoshiyuki , Toriyama Motohiro , Kawamoto Yukari , Suzuki Takahiro , Nishizawa Kaori , Nagata Fukue , Mucalo M R
Published: March 2006

The formation of a calcium-strontium apatite solid solution precursor via mechanochemical method was described. The precursor is formed by a process of ball-milling of a slurry consisting of a mixture of the starting materials; CaHPO4·2H2O, CaCO3, SrHPO4 and Sr(OH)4·8H2O in a zirconia pot mill for 24 h in the presence of water at room temperature over the entire Ca/(Ca+Sr) compositional range. Calcium-stontium apatite precursor obtained from ball-milling began to change to calcium-stontium apatite upon heating at temperature over 500 °C.
Tetraarylporphyrins as Probes for Studying Mechanism of Inclusion-complex Formation of Cyclodextrins. Effect of Microscopic Environment on Inclusion of Ionic Guests
Authors: Kano Koji , Tanaka Naoya , Minamizono Hideo , Kawakita Yoshihiro
Published: March 2006

The pKa values and the 1H NMR spectra of tetraarylporphyrins in the presence of cyclodextrins suggest that the microscopic environment of the positively polarized cavity of cyclodextrin promotes the inclusion of the anionic guest and prohibits the penetration of the cationic guest into the cyclodextrin cavity.
Inverse Substituent Effect on 77Se NMR Chemical Shifts in Naphthalene Systems with Linear 4c-6e Se4 Bond: 1-[8-(p-YC6H4Se)C10H6]SeSe[C10H6(SeC6H4Y-p)-8′]-1′ vs. 1-(MeSe)-8-(p-YC6H4Se)C10H6
Authors: Nakanishi Warô , Hayashi Satoko , Yamaguchi Hitomi
Published: March 2006

The substituent effect on δ(1Se) vs. δ(8Se) in bis[8-arylselanyl)naphthyl] diselenides (1) was oppsite to that for 1-(methylselanyl)-8-(phenylselanyl)naphthalene and its p-substituted derivatives. The observation must be the reflection of the 4c-6e interaction between the p-orbitals of the four Se atoms in 1.
ESR Studies on Poly(methyl acrylate) Radicals to Estimate Their Dominant Structure
Authors: Sugiyama Yoshio
Published: March 2006

Electron Spin Resonance (ESR) examinations of the propagating radicals in the polymerization of methyl acrylate (MA) and methyl acrylate-α-d (MA-d) in the frozen state have been made. Selective deuteration of MA showed that the propagating radicals have the chain-end (I) and not the mid-chain (II) structure. The stable conformation of poly (methyl acrylate) (poly (MA)) radical was also determined.
Double Mediatory System Involving a Flavin Analog and a p-Benzoquinone Derivative for Photoinduced Electrochemical Oxidation of Benzyl Alcohol to Benzaldehyde in Acetonitrile
Authors: Ishikawa Masashi , Okimoto Hiroyuki , Morita Masayuki , Matsuda Yoshiharu
Published: March 2006

The photoinduced electrochemical oxidation of benzyl alcohol to benzaldehyde in acidic acetonitrile proceeded with practically 100% product selectivity and ca. 100% current efficiency under visible-light irradiation in the presence of riboflavin-2′,3′,4′,5′-tetraacetate (RF) as a mediator. A double mediatory system involving duroquinone as well as RF resulted in remarkable acceleration of the benzaldehyde formation with maintenance of both the high product selectivity and high current efficiency.
Investigation on the Electron-transfer Interaction of the Two Ferrocene Moieties Bridged by Ni2+ or Cu2+ and Its Mixed-valence Complexes
Authors: Yu Zhi , Zhou Yuan , Yang Wei , Tian Yunpeng , Duan Cun-ying , Liu Rongchuan , You Xiaozeng
Published: March 2006

Investigation of the new mixed-valence trinuclear complexes of FcMFc (M = Ni, Cu) indicates that intramolecular long-range charge transfer for FcNiFc complex processes in timescale 1.6•106 s−1 through a long bridge including a coordinated bond at room temperature.
Synthesis and Properties of N,N′-Bis(1-pyrenylmethyl)-1,4,10,13-tetraoxa-7,16-diaza-cyclooctadecane. Metal Ion-Indused Monomer and Excimer Emission Enhancement
Authors: Kubo Kanji , Sakurai Tadamitsu
Published: March 2006

N,N′-Bis(1-pyrenylmethyl)-4,13-diaza-18-crown-6 ether was found to display unique photophysical properties in the presence of the guest metal salts. The binding of metal ions to the azacrown ether cavity inhibited the exciplex formation and changed the distance between two pyrenyl groups. This caused not only the emission-intensity anhancement but also a large change in the monomer/excimer fluorescence-intensity ratio.
Synthesis, Structural Characterization, and Interconversion of S-Bridged Dinuclear and Hexanuclear Complexes Composed of cis(S)-[Co(aet)2(en)]+ and Trigonal-Bipyramidal Cadmium(II) (aet = 2-Aminoethanethiolate, en = Ethylenediamine)
Authors: Konno Takumi , Okamoto Ken-ichi
Published: March 2006

The reaction of [Ni{Co(aet)2(en)}2]4+ (1) with excess CdCl2 gave an S-bridged CoIIICdII dinuclear complex, [CdCl3{Co(aet)2(en)}] (2), which is interconvertible to a CoIII4CdII2 hexanuclear complex, [Cd2Cl{Co(aet)2(en)}4]7+ (3). X-Ray analyses of 2 and 3(NO3)7 indicated that each Cd atom in the complexes has a trigonal-bipyramidal geometry.
Novel Aggregation of fac(S)-[Rh(aet)3] by Square-Planar Palladium(II): Crystal Structure of Spontaneously Resolved RhIII3PdII2 Pentanuclear Complex [Pd{Pd(aet)}{Rh(aet)2}{Rh(aet)3}2]Br4 (aet = 2-Aminoethanethiolate)
Authors: Konno Takumi , Sasaki Chieko , Okamoto Ken-ichi
Published: March 2006

The reaction of fac(S)-[Rh(aet)3] (aet = NH2CH2CH2S−) with PdII gave a novel S-bridged RhIII3PdII2 pentanuclear complex, [Pd{Pd(aet)}{Rh(aet)2}{Rh(aet)3}2]4+ (1), of which bromide salt was spontaneously resolved. 1 was converted into [Pd{Pd(aet)}{Rh(aet)(NH2CH2CH2SCH3)}{Rh(aet)3}2]5+ (2) by methylation reaction.
Electrochemical Reactivity of LiFePO4 Prepared by Hydrothermal Method
Authors: Dokko Kaoru , Koizumi Shohei , Kanamura Kiyoshi
Published: February 2006

LiFePO4 was prepared by hydrothermal method starting from CH3COOLi, FeSO4, and (NH4)2HPO4 at 170 °C. The particle size of the obtained LiFePO4 was about 3 μm. The performance of the LiFePO4 as a positive electrode material for rechargeable lithium battery was evaluated in an organic electrolyte. The LiFePO4 exhibited a discharge capacity of 145 mA h g−1 at the electrode potential of 3.5 V vs Li/Li+.
Patent Protection, Complementary Assets, and Firms’ Incentives for Technology Licensing
Authors: Arora Ashish , Ceccagnoli Marco
Published: March 2006

This paper analyzes the relationship between technology licensing and the effectiveness of patent protection. Using the 1994 Carnegie Mellon survey on industrial research and development (R&D) in the United States, we develop and test a simple structural model in which the patenting and licensing decisions are jointly determined. We find that increases in the effectiveness of patent protection increases licensing propensity, but only when the firm lacks specialized complementary assets required to commercialize new technologies. In contrast, for firms with specialized complementary assets, increases in patent effectiveness increase patenting propensity but reduce the propensity to license. We present systematic cross-industry empirical support for the proposition that intellectual property protection is a key determinant of the vertical boundaries of the firm and the market for technology but that its impact is mediated by a firm’s ownership of specialized complementary assets.
Continual Corporate Entrepreneurial Search for Long-Term Growth
Authors: Bhardwaj Gaurab , Camillus John C. , Hounshell David A.
Published: March 2006

This paper examines how established firms conduct continual entrepreneurial search for possibilities for long-term growth. Drawing on comprehensive internal documents of the DuPont Company over a 20-year period, we develop a search process that is a departure from frequent depictions of search as local or random. Longitudinal field data show that corporate entrepreneurs follow a “moving, anchored search” for growth possibilities. Employing this framework as lens, we develop propositions. We find that corporate entrepreneurs are more likely to conduct search in new domains following events that cause them to expect future performance to change significantly and lastingly. This is in contrast to the literature that has typically modeled the initiation of search as a response to poor past performance. Because new domains are unexplored territories for corporate entrepreneurs, they utilize transitional levers that they perceive will facilitate the move from existing domains to new ones. These perceived transitional levers, however, typically prove inaccurate or incomplete. Content within domains is searched using anchors whose locations and numbers change. The combination of search process and content searched influences the particular growth possibilities discovered and created. Search and pursuit of growth possibilities is accompanied by the creation of new knowledge and new capabilities.
Multistage Selection and the Financing of New Ventures
Authors: Eckhardt Jonathan T. , Shane Scott , Delmar Frédéric
Published: March 2006

Using a random sample of 221 new Swedish ventures initiated in 1998, we examine why some new ventures are more likely than others to successfully be awarded capital from external sources. We examine venture financing as a staged selection process in which two sequential selection events systematically winnow the population of ventures and influence which ventures receive financing. For a venture to receive external financing its founders must first select it as a candidate for external funding, and then a financier must fund it. We find evidence that founders select ventures as candidates for external finance based on their perceptions of market competition, market growth, and employment growth, while financiers base funding decisions on objective verifiable indicators of venture development, such as the completion of organizing activities, marketing activities, and the level of sales of the venture. Our findings have implications for venture financing and evolutionary theories of social processes.
Social Capital, Geography, and Survival: Gujarati Immigrant Entrepreneurs in the U.S. Lodging Industry
Authors: Kalnins Arturs , Chung Wilbur
Published: March 2006

Immigrant entrepreneurs often rely on their group’s local social capital in their new home market to establish and maintain their businesses. In particular, immigrant entrepreneurs with few resources of their own receive help from those possessing more resources. Supporting these arguments using the empirical setting of Gujarati immigrant entrepreneurs in the lodging industry, we find that the likelihood of survival of an immigrant entrepreneur’s hotel increases when surrounded by higher counts of branded hotels (representing high-resource establishments) owned by individuals from their ethnic group but is unaffected by unbranded motels (representing low-resource establishments) owned by members of their ethnic group or by branded hotels owned by individuals from other ethnic groups. These results isolate and reinforce the importance of social capital not only for immigrant entrepreneurs but also more generally for any entrepreneurs belonging to ethnic, professional, religious, or social groups.
Perceived Efficacy, Indications, and Information Sources for Medically Indigent Patients and Their Healthcare Providers Regarding Dietary Supplements
Authors: Clay Patrick G , Glaros Alan G , Clauson Kevin A
Published: March 2006

Background:

Evidence exists that medically indigent and minority patients use dietary supplements at rates as high or higher than that of the general population. Safety concerns regarding the use of dietary supplements are further exacerbated by a suboptimal level of patient disclosure and provider inquiry.

Objective:

To determine dietary supplement use, indications, perceived efficacy, and information sources of patients and providers using a pilot study in a clinic for the medically indigent.

Methods:

Five hundred self-administered patient surveys and 50 healthcare provider surveys were made available to any patient at a free health clinic in Kansas City, MO. Surveys were collected and descriptive analyses were performed.

Results:

Three hundred eleven patient surveys were returned. Of the 37.3% (116/311) of respondents who had used dietary supplements, 13.8% (n = 16) had 10 comorbid conditions. Ninety-six dietary supplements were used for 8 medical condition categories. The 9 agents most frequently reported used were garlic (n = 32), aloe/green tea (n = 27 each), chamomile/echinacea (n = 24 each), St. John's wort (n = 22), ginseng (n = 18), and cranberry/Ginkgo biloba (n = 17 each). Patients reported a broad range of indications for taking dietary supplements. Patients reported (mean ± SD) 2.37 ± 4.23 agents as effective and 0.78 ± 1.73 as ineffective or harmful. Provider surveys revealed that 60% (21/35) and 74% (26/35) were currently or had ever used dietary supplements, respectively. Fifty-seven percent (20/35) of providers reported attending educational programs on dietary supplements, and providers perceived patient supplement use to be most influenced by advertisements (40%) and friends (40%).

Conclusions:

The medically indigent population uses a wide variety of dietary supplements. There is little consistency in perceived indications, which may prevent clinicians from accurately predicting specific herbal use rationale given any individual's or population's set of comorbid conditions. Clinicians are encouraged to accurately determine their individual practice setting's use pattern.
Dalbavancin: A New Option for the Treatment of Gram-Positive Infections
Authors: Lin Shu-Wen , Carver Peggy L , DePestel Daryl D
Published: March 2006

Objective:

To review the pharmacology, microbiology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of dalbavancin, a new semisynthetic lipoglycopeptide.

Data Sources:

A MEDLINE search, restricted to the English language, was conducted from 1966 through January 2006. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society of Microbiology, and the Infectious Diseases Society of America from 2000 to 2005 and information available from the manufacturer's Web site.

Study Selection and Data Extraction:

In vitro and preclinical studies, as well as Phase I, II, and III clinical trials, were evaluated to summarize the microbiology, pharmacology, clinical efficacy, and safety of dalbavancin. All published trials and abstracts citing dalbavancin were selected.

Data Synthesis:

Dalbavancin, a novel lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has in vitro activity against a variety of gram-positive organisms, but no activity against gram-negative or vancomycin-resistant enterococci that possess VanA gene. Due to its prolonged half-life (6–10 days), dalbavancin can be administered intravenously once weekly. In Phase II and III clinical trials, dalbavancin was effective and well tolerated for the treatment of skin and soft-tissue infections, catheter-related bloodstream infections, and skin and skin-structure infections. To date, adverse events are mild and limited; the most common include pyrexia, headache, nausea, oral candidiasis, diarrhea, and constipation.

Conclusions:

Dalbavancin appears to be a promising antimicrobial agent for the treatment of gram-positive infections. A new drug application was filed with the Food and Drug Administration (FDA) in December 2004. The FDA issued an approvable letter in 2005 for dalbavancin. If approved, dalbavancin is expected to be launched in the first quarter of 2006.
Increased Sensitivity to Warfarin After Heart Valve Replacement
Authors: Rahman Mesbah , BinEsmael Taha M , Payne Nicola , Butchart Eric G
Published: March 2006

Background:

The dosage requirement of warfarin to achieve a given international normalized ratio (INR) often varies considerably between the immediate postoperative period and long-term follow-up in patients with prosthetic heart valves, leading to INR instability.

Objective:

To document the extent of warfarin sensitivity in a prospective study of patients receiving heart valve replacements.

Methods:

Clinical and laboratory data regarding anticoagulation for 111 patients who received warfarin following heart valve replacement were collected during their hospital stay (induction period) and between 1 and 3 months after surgery (follow-up period).

Results:

Mean patient age was 65.39 ± 10.55 years (range 29–85), with 66 men. The mean INR value during the follow-up period was, on average, 0.21 higher than the induction period (2.81 ± 0.5 vs 2.6 ± 0.6; p = 0.007). The mean follow-up warfarin dose was 1.54 mg higher than the mean induction warfarin dose (5.09 ± 2.03 vs 3.55 ± 1.94 mg; p < 0.001). The warfarin dose index, which indicates relative sensitivity of warfarin, decreased from 1.16 to 0.65 (p < 0.001). Although the INR values during the induction and follow-up periods were similar, the dose requirement in the follow-up period was, on average, 43% higher than that of the induction period.

Conclusions:

Immediately after heart valve replacement, patients are more sensitive to warfarin and should receive a lower warfarin dose during the initial phase of oral anticoagulation treatment. This enhanced sensitivity decreases with time. Patients require frequent monitoring and are likely to need an increase in the warfarin dose to avoid insufficient anticoagulation during the early follow-up period.
Treatment of Hepatitis C in HIV-Coinfected Patients
Authors: Hughes Christine A , Shafran Stephen D
Published: March 2006

Objective:

To review the current management of hepatitis C virus (HCV) in persons coinfected with HIV.

Data Sources:

A MEDLINE search (1966–February 2006) was conducted, using key words such as HIV, human immunodeficiency virus, hepatitis C, interferon, pegylated interferon, and therapy. Article bibliographies and conference abstracts were also reviewed to identify relevant studies.

Study Selection and Data Extraction:

Studies that examined HCV treatment in individuals coinfected with HIV and articles that focused on HCV/HIV coinfection were considered for this review.

Data Synthesis:

Coinfection with HIV leads to a more rapid and severe course of HCV-related liver disease. Treatment of HCV with pegylated interferon (PEG-IFN) and ribavirin therapy is relatively well tolerated in individuals coinfected with HIV, with overall sustained virologic response (SVR) rates of 27–40%. High relapse rates and poor response in HCV-genotype 1 contribute to the lower SVR in coinfected individuals compared with HCV monoinfection. Treatment of HCV is more complicated in HIV-infected persons due to increased risk of myelosuppression, drug interactions, hepatotoxicity of antiretroviral therapy, and the relative contraindication to interferon therapy in advanced HIV disease. Current guidelines recommend that all HIV-positive patients with chronic HCV infection be considered as treatment candidates for anti-HCV therapy due to the higher risk of liver disease progression. Further studies are needed, however, to define the appropriate dose and duration of therapy in HCV/HIV-coinfected individuals.

Conclusions:

Response to treatment with PEG-IFN and ribavirin is poorer in patients coinfected with HCV/HIV than in those infected with HCV alone. The benefits of anti-HCV therapy, including viral eradication, need to be weighed against the risks of adverse effects and drug-drug interactions between anti-HCV and antiretroviral medications.
Appeals System and Its Outcomes in National Health Insurance in Taiwan
Authors: Lin Swu-Jane , Kuo Shin-Chen , Kao Yang Yea-Huei
Published: March 2006

Background:

Prior authorization has been used extensively as one of the mechanisms to control costs and ensure quality of care by the National Health Insurance (NHI) plan in Taiwan. An appeals system, the Dispute Mediation Committee (DMC), independent of the NHI, is available for interested parties to dispute denials of prior authorization. Currently, medications for Alzheimer's disease constitute the largest category of appeals.

Objective:

To describe the appeals system and analyze outcomes of cases of medications for Alzheimer's disease submitted to the Bureau of NHI (BNHI) for prior authorization and to the DMC for appeals.

Methods:

Prescriptions of donepezil and rivastigmine submitted for prior authorization from 2000 through 2002 were analyzed. Cases denied prior authorization and later submitted as appeals to the DMC were summarized with descriptive and bivariate methods.

Results:

A total of 12237 cases of donepezil and 6975 cases of rivastigmine were submitted to the BNHI for prior authorization; among them, 72.6% of donepezil and 66.5% of rivastigmine cases received authorization. Among the thousands of cases denied prior authorization, 124 appealed to the DMC for dispute resolution. The result of the majority of the appeals (111 [89.5%]) was to uphold the BNHI denial decision. Most of the appeals were denied because of the lack of appropriate exclusion of other possible causes of dementia.

Conclusions:

Most appeals were again denied after expert review. Better education concerning utilization guidelines and a platform for insurer, insuree, and physician to dialog are needed to improve the effectiveness and efficiency of the appeals system.
Cost Analysis of Erythropoietic-Stimulating Therapy Dosing in Oncology Inpatients
Authors: Killian Aaron D , Gupta Vikas , Goetz Alisa E
Published: March 2006

Background:

Inpatient costs associated with different erythropoietic-stimulating therapy regimens have not been compared in an oncology setting.

Objective:

To conduct a cost analysis of different regimens of epoetin alfa (EPO) and darbepoetin alfa (DARB) in an inpatient oncology setting.

Methods:

A retrospective evaluation of oncology diagnosis-related group discharges during 2003, in 30 community hospitals, identified EPO treatment patterns. Wholesale acquisition costs were determined for patients who received EPO 40 000 units or more once weekly. Potential differences in costs were calculated using conversion ratios for an equivalent EPO dose 3 times weekly or DARB dose once weekly (EPO:DARB ratio 260:1, approximating DARB 150 μg once weekly). A sensitivity analysis was performed using an EPO:DARB ratio of 400:1, approximating DARB 100 μg once weekly (1.5 μg/kg).

Results:

Among the 1410 EPO doses administered (n = 677 pts.), a dose of 40000 units or more was used 44% of the time (n = 311 pts.), with dosing initiated on average 5.6 days after admission. For these 311 evaluable patients, switching from EPO 40 000 units once weekly to EPO 10 000 units 3 times weekly reduced per-patient and total drug acquisition costs by approximately 50% ($704 vs $359 and $218 938 vs $111 615, respectively). Relative to EPO once weekly, switching patients to DARB resulted in increased drug acquisition costs at the 260:1 conversion and lower costs at the 400:1 conversion. However, EPO 3 times weekly remained the least costly option by 44–63%. The cost-savings realized with EPO 10000 units 3 times weekly increased with longer duration of hospitalization.

Conclusions:

In an inpatient setting, use of EPO 10000 units 3 times weekly may minimize expenditures associated with treatment of cancer-related anemia using erythropoietic-stimulating therapies.
Formulary Forum: Sodium Oxybate for Cataplexy
Authors: Lemon Michael D , Strain Joe D , Farver Debra K
Published: March 2006

Objective:

To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, precautions, dosing recommendations, and patient counseling of sodium oxybate for the treatment of cataplexy in patients with narcolepsy.

Data Sources:

OVID and PubMed databases were searched (1966–January 2006) using the key words sodium oxybate, gamma-hydroxybutyrate, narcolepsy, and cataplexy. Only English-language articles were selected.

Study Selection and Data Extraction:

All information on sodium oxybate related to narcolepsy and cataplexy was considered. Study selection included human trials evaluating safety and efficacy of sodium oxybate for the treatment of cataplexy.

Data Synthesis:

Sodium oxybate is approved by the Food and Drug Administration for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. In placebo-controlled trials, sodium oxybate demonstrated efficacy in reducing the number of cataplexy attacks. The dosing regimen includes a split dose given at bedtime and 2.5–4 hours later due to its short elimination half-life. The drug is generally well tolerated, with headache, nausea, dizziness, pain, and somnolence being the most common adverse events.

Conclusions:

Sodium oxybate is safe and effective for the treatment of cataplexy. Potential disadvantages include a multiple dosing regimen, abuse potential, cost, and a closed distribution system. Potential advantages demonstrated in clinical trials include significant decreases in the number of weekly cataplexy attacks, improvement in daytime sleepiness, and improvement in the Clinical Global Impression of Change score and nighttime awakenings. Overall, sodium oxybate provides a new option for the treatment of cataplexy.
Effect of Buprenorphine and Antiretroviral Agents on the QT Interval in Opioid-Dependent Patients
Authors: Baker Jennifer R , Best AI M , Pade Patricia A , McCance-Katz Elinore F
Published: March 2006

Background:

Cardiac arrhythmias have been linked to treatment with methadone and levacetylmethadol. HIV-positive patients often have conditions that place them at risk for QT interval prolongation including HIV–associated dilated cardiomyopathy, coronary artery disease as a consequence of highly active antiretroviral (ARV) therapy–associated metabolic syndrome, and uncorrected electrolyte abnormalities. As of February 14, 2006, no cases of adverse events related to QT interval prolongation have been reported in patients receiving buprenorphine, an opioid partial agonist and the newest drug approved for the treatment of opioid dependence.

Objective:

To evaluate the effects of buprenorphine/naloxone alone and in combination with 1 of 5 ARV agents (efavirenz, nelfinavir, delavirdine, ritonavir, lopinavir/ritonavir) on the QT interval.

Methods:

This study was prospective, open-label, and within-subject in design, with subjects serving as their own controls. In 50 HIV-negative, opioid-dependent subjects, electrocardiogram recordings were obtained at baseline, after receiving buprenorphine/naloxone for 2 weeks, and then following buprenorphine/naloxone plus ARV administration for 5–15 days at steady-state. QTc interval measurements were compared using mixed-model, repeated-measures ANOVA. Recent cocaine use and gender were considered covariates.

Results:

Buprenorphine/naloxone alone and often in the presence of evidence for recent use of cocaine did not significantly alter the QT interval (p = 0.612). Buprenorphine/naloxone in combination with ARVs caused a statistically, but not clinically, significant increase (p = 0.005) in the QT interval. Subjects receiving buprenorphine/naloxone in combination with either delavirdine or ritonavir had the greatest increase in QTc intervals.

Conclusions:

Prolonged QT intervals were not observed in opioid-dependent subjects receiving buprenorphine/naloxone alone. QT interval increases were observed with buprenorphine/naloxone in combination with either delavirdine or ritonavir, which inhibit CYP3A4.
Should Drug Therapy Be Personalized Based on Race?
Authors: Vivian Eva M
Published: March 2006

The A-HeFT (African American Heart Failure Trial) showed that isosorbide/hydralazine was associated with significant reductions in mortality in African Americans with heart failure compared with placebo. The results of a recently published genetic substudy identified a gene variant related to nitric oxide synthase production that attributed to the treatment response observed in patients enrolled in the A-HeFT. This finding suggests that isosorbide/hydralazine's ability to improve heart failure outcomes is tied to a genetic trait that may be more prevalent in African Americans than whites, but is not necessarily related to perceived race.
Identification of mRNA Markers for Molecular Staging of Lymph Nodes in Colorectal Cancer
Authors: Xi Liqiang , Gooding William , McCarty Kenneth , Godfrey Tony E , Hughes Steven J
Published: March 2006

Background: One evolving approach to improved prognostication of cancer patients is the identification of previously occult disease by use of quantitative reverse transcription-PCR. Surprisingly, no systematic analysis of potential mRNA markers for colorectal cancer has been reported. We therefore performed an extensive mRNA marker survey for colorectal cancers.

Methods: We identified potential markers through literature and database searches. We analyzed all markers by quantitative reverse transcription-PCR on a limited set of primary tumors and benign lymph nodes. Selected markers were further evaluated on a larger tissue set with positive lymph nodes.

Results: We evaluated 43 markers and undertook further analysis of 6 in the secondary screening. Five gene markers—CDX1, carcinoembryonic antigen (CEA), CK20, TACSTD1, and Villin1 (VIL1)—provided perfect classification of lymph node status.

Conclusions: Several mRNA markers are capable of providing exceptionally accurate characterization of lymph node status in colorectal cancer. An automated, multimarker, quantitative reverse transcription-PCR assay for characterization of lymph nodes from colorectal cancer patients may be useful for improved staging and therapeutic decision making in colorectal cancer.
Development of a Supermartensitic Stainless Steel Microalloyed with Niobium
Authors: Rodrigues CAD , Lorenzo PLD , Sokolowski A , Barbosa A , Rollo JMDA
Published: February 2006

The new class of supermartensitic stainless steels (SMSS) exhibits higher mechanical strength, corrosion resistance, and weldability properties when compared with conventional martensitic stainless steels. This paper presents the results of detailed investigations on 12,50Cr-5,36Ni-2,10Mo-0,20Nb steels that were obtained in a conventional furnace under vacuum and subsequently hot rolled and heat treated similar to the procedure used in production of conventional stainless steels. The microstructural characterization was carried out by optical microscopy (OM), scanning electron microscopy (SEM), and hot stage microscopy. Phase transformations and the effects from heat treatment were examined using a dilatometer. The microstructure, after quenching and tempering, is typical of a martensite matrix with carbonitride of Nb (C,N) small precipitates (40 nm) and mechanical properties of 26RC hardness, 910 MPa tensile strength, 860 MPa yield strength, 20,8% elongation and 199J Charpy impact.
Functional Analysis of Circadian Pacemaker Neurons inDrosophila melanogaster
Authors: Rieger Dirk , Shafer Orie Thomas , Tomioka Kenji , Helfrich-Förster Charlotte
Published: March 2006

The molecular mechanisms of circadian rhythms are well known, but how multiple clocks within one organism generate a structured rhythmic output remains a mystery. Many animals show bimodal activity rhythms with morning (M) and evening (E) activity bouts. One long-standing model assumes that two mutually coupled oscillators underlie these bouts and show different sensitivities to light. Three groups of lateral neurons (LN) and three groups of dorsal neurons govern behavioral rhythmicity ofDrosophila. Recent data suggest that two groups of the LN (the ventral subset of the small LN cells and the dorsal subset of LN cells) are plausible candidates for the M and E oscillator, respectively. We provide evidence that these neuronal groups respond differently to light and can be completely desynchronized from one another by constant light, leading to two activity components that free-run with different periods. As expected, a long-period component started from the E activity bout. However, a short-period component originated not exclusively from the morning peak but more prominently from the evening peak. This reveals an interesting deviation from the original Pittendrigh and Daan (1976) model and suggests that a subgroup of the ventral subset of the small LN acts as “main” oscillator controlling M and E activity bouts inDrosophila.
Estrogen Alters Spine Number and Morphology in Prefrontal Cortex of Aged Female Rhesus Monkeys
Authors: Hao Jiandong , Rapp Peter R. , Leffler Abba E. , Leffler Shoshana R. , Janssen William G. M. , Lou Wendy , McKay Heather , Roberts Jeffrey A. , Wearne Susan L. , Hof Patrick R. , Morrison John H.
Published: March 2006

Long-term cyclic treatment with 17β-estradiol reverses age-related impairment in ovariectomized rhesus monkeys on a test of cognitive function mediated by the prefrontal cortex (PFC). Here, we examined potential neurobiological substrates of this effect using intracellular loading and morphometric analyses to test the possibility that the cognitive benefits of hormone treatment are associated with structural plasticity in layer III pyramidal cells in PFC area 46. 17β-Estradiol did not affect several parameters such as total dendritic length and branching. In contrast, 17β-estradiol administration increased apical and basal dendritic spine density, and induced a shift toward smaller spines, a response linked to increased spine motility, NMDA receptor-mediated activity, and learning. These results document that, although the aged primate PFC is vulnerable in the absence of factors such as circulating estrogens, it remains responsive to long-term cyclic 17β-estradiol treatment, and that increased dendritic spine density and altered spine morphology may contribute to the cognitive benefits of such treatment.
Lipid Binding Regulates Synaptic Targeting of PICK1, AMPA Receptor Trafficking, and Synaptic Plasticity
Authors: Jin Wenying , Ge Woo-Ping , Xu Junyu , Cao Mian , Peng Lisheng , Yung Wingho , Liao Dezhi , Duan Shumin , Zhang Mingjie , Xia Jun
Published: March 2006

The targeting and surface expression of membrane proteins are critical to their functions. In neurons, synaptic targeting and surface expression of AMPA-type glutamate receptors were found to be critical for synaptic plasticity such as long-term potentiation and long-term depression (LTD). PICK1 (protein interacting with C kinase 1) is a cytosolic protein that interacts with many membrane proteins, including AMPA receptors via its PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain. Its interactions with membrane proteins regulate their subcellular targeting and surface expression. However, the mechanism by which PICK1 regulates protein trafficking has not been fully elucidated. Here, we show that PICK1 directly binds to lipids, mainly phosphoinositides, via its BAR (Bin/amphiphysin/Rvs) domain. Lipid binding of the PICK1 BAR domain is positively regulated by its PDZ domain and negatively regulated by its C-terminal acidic domain. Mutation of critical residues of the PICK1 BAR domain eliminates its lipid-binding capability. Lipid binding of PICK1 controls the subcellular localization of the protein, because BAR domain mutant of PICK1 has diminished synaptic targeting compared with wild-type PICK1. In addition, the BAR domain mutant of PICK1 does not cluster AMPA receptors. Moreover, wild-type PICK1 enhances synaptic targeting of AMPA receptors, whereas the BAR domain mutant of PICK1 fails to do so. The BAR domain mutant of PICK1 loses its ability to regulate surface expression of the AMPA receptors and impairs expression of LTD in hippocampal neurons. Together, our findings indicate that the lipid binding of the PICK1 BAR domain is important for its synaptic targeting, AMPA receptor trafficking, and synaptic plasticity.
Rolling Blackout Is Required for Synaptic Vesicle Exocytosis
Authors: Huang Fu-De , Woodruff Elvin , Mohrmann Ralf , Broadie Kendal
Published: March 2006

Rolling blackout (RBO) is a putative transmembrane lipase required for phospholipase C-dependent phosphatidylinositol 4,5-bisphosphate–diacylglycerol signaling inDrosophilaneurons. Conditional temperature-sensitive (TS)rbomutants display complete, reversible paralysis within minutes, demonstrating that RBO is acutely required for movement. RBO protein is localized predominantly in presynaptic boutons at neuromuscular junction (NMJ) synapses and throughout central synaptic neuropil, andrboTS mutants display a complete, reversible block of both central and peripheral synaptic transmission within minutes. This phenotype appears limited to adults, because larval NMJs do not manifest the acute blockade. Electron microscopy of adultrboTS mutant boutons reveals an increase in total synaptic vesicle (SV) content, with a concomitant shrinkage of presynaptic bouton size and an accumulation of docked SVs at presynaptic active zones within minutes. Genetic tests reveal a synergistic interaction betweenrboandsyntaxin1ATS mutants, suggesting that RBO is required in the mechanism ofN-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated SV exocytosis, or in a parallel pathway necessary for SV fusion. TherboTS mutation does not detectably alter SNARE complex assembly, suggesting a downstream requirement in SV fusion. We conclude that RBO plays an essential role in neurotransmitter release, downstream of SV docking, likely mediating SV fusion.