bluuebunny/crossref_metadata_2025 huggingface dataset:
The Polarized ESR Spectrum of 1-Methyl-3-methoxycarbonylpyridinyl Radical
Authors: Akiyama Kimio , Ikegami Yusaku
Published: July 2006

The CIDEP spectrum of 1-methyl-3-methoxycarbonylpyridinyl radical has been measured by time-resolved ESR method. The radical is generated from its dimer by photodissociation through the radical pair mechanism from the singlet state.
Crystal Structures of 2,7-Bis(methylthio)-1,6-dithiapyrene (MTDTPY) and 2,3:7,8-Bis(ethanedithio)-1,6-dithiapyrene (ETDTPY). Sheet-Like Networks of Dimeric Pairs
Authors: Nakasuji Kazuhiro , Sasaki Mitsuru , Kotani Tomoyuki , Murata Ichiro , Kawamoto Atsushi , Tanaka Jiro
Published: July 2006

The crystal structures of methylthio and ethanedithio substituted peri-condensed Weitz type donors, bis(methylthio)dithiapyrene and bis(ethanedithio)dithiapyrene, showed sheet-like networks of dimeric pairs of the donor molecules.
A New α-Iodination of Ketones Using Iodine–Cerium(IV) Ammonium Nitrate
Authors: Horiuchi C Akira , Kiji Shinji
Published: July 2006

Direct α-iodination of some ketones using iodine–cerium(IV) ammonium nitrate in acetic acid or methanol, gave the corresponding α-iodoketone in high yield. In the case of 2-pentanone, 4-methyl-2-pentanone, 2-hexanone, and 2-heptanone in methanol, the regioselective products were obtained.
Raman Spectral Change of Crown Ethers and Related Polyethylene Glycol Dialkyl Ethers Due to Accommodation of Water
Authors: Fukushima Kunio , Ito Masami , Sakurada Koji , Shiraishi Shigeki
Published: July 2006

Raman spectra of crown ethers and related polyethylene glycol dialkyl ethers in solutions were measured. The spectra showed remarkable characteristics, which are interpreted to be due to accommodation of water. Conformations of the crowns and the ethers accommodating water are similar to those in their complexes with cations.
Photochemical CO2 Reduction by an NADH Model Compound in the Presence of [Ru(bpy)3]2+ and [Ru(bpy)2(CO)2]2+ (bpy = 2,2′-bipyridine) in H2O / DMF
Authors: Ishida Hitoshi , Tanaka Koji , Tanaka Toshio
Published: July 2006

Photochemical conversion of CO2 to CO and HCOO− was achieved by using an NADH model compound, 1-benzyl-1,4-dihydronicotinamide (BNAH), as an electron donor in the presence of [Ru(bpy3]2+ (bpy = 2,2′-bipyridine) and [Ru(bpy)2(CO)2]2+ in H2O / DMF. The quantum yields for the CO and HCOO− formation attained 14.8 and 2.7%, respectively, in H2O/DMF (1:9 v/v).
Preparation and Structural Characterization of Binuclear Manganese(III) Complexes with 1,5-Bis(salicylideneamino)-3-pentanol and Its Derivatives
Authors: Mikuriya Masahiro , Kida Sigeo , Murase Ichiro
Published: July 2006

Three binuclear manganese(III) complexes with the title Schiff base ligands have been prepared and characterized. X-Ray structure analysis of [Mn2(Lb) (CH3O) (CH3COO) (CH3OH) (ClO4)] (H3Lb = 1,5-bis(5-chlorosalicylideneamino)-3-pentanol) has revealed that the two manganese ions are bridged by the alkoxide oxygen atom of the Schiff base ligand, the methoxide oxygen atom, and the oxygen atoms of the acetate ion with the Mn–Mn separation of 2.921(2) Å.
Preparation of Highly Active Sulfided Mo/Al2O3 Catalyst for Hydrogenation of Cyclopropane and Olefins
Authors: Sugioka Masatoshi , Kanazuka Takaji
Published: July 2006

The effect of sulfiding with H2S on the activity of Mo/Al2O3 catalyst in the hydrogenation of cyclopropane and various olefins was investigated. Extremely high active sulfided Mo/Al2O3 catalyst was prepared by sulfiding of Mo/Al2O3 with H2S followed by evacuation under high vacuum at 450 °C.
Synergetic Ligand Effect in the Hydrogen Exchange Reaction of Propene over Pd–Cu and Pt–Cu Alloy Catalysts
Authors: Naito Shuichi , Tanimoto Mitsutoshi
Published: July 2006

Marked changes of reaction intermediates on alloying were disclosed by the microwave spectroscopic analysis of the monodeuteriopropene formed during C3H6–C3D6 exchange reaction over Pd–Cu and Pt–Cu alloy catalysts.
An Electrochemical Evidence for the Participation of Iron(IV) Porpyrin Species in the C–C Bond Cleavage of 1,2-Diaryl-1,2-ethanediol
Authors: Okamoto Tadashi , Sasaki Ken , Takano Mikio , Oka Shinzaburo
Published: July 2006

Cyclic voltammogram of a mixture of tetraphenylporphrinatoiron(III) and 1,2-bis(4-methoxyphenyl)ethane-1,2-diol in dichloromethane showed a catalytic wave at the potential corresponding to the oxidation of Fe(III) to Fe(IV). The rate of reaction of Fe(IV) with the diol following the electrochemical process was determined.
Ion-pair Extraction of Gallium(III) from Hydrochloric Acid with Various Methoxy-substituted Triarylphosphines
Authors: Yamashoji Yuko , Matsushita Takayuki , Wada Masanori , Shono Toshiyuki
Published: July 2006

A series of methoxy substituted triarylphosphines RnPh3-np where R can be 2-MeOPh, 4-MeOPh, 2,6-MeOPh, and 2,4,6-MeOPh and n=1, 2, and 3, has been prepared and employed as extractants for gallium(III) from hydrochloric acid solutions. Their extractabilities for gallium(III) were found to become more effective with their increased basicities.
The Structure of a New Sesquiterpene Glycoside from the Flowers of Pittosporum tobira
Authors: Suga Takayuki , Munesada Kiyotaka , Ogihara Kazuhito , Morita Tohru , Shirai Takayuki
Published: July 2006

A new sesquiterpene glycoside, named pittosporatobiraside, was isolated from the flowers of Pittosporum tobira. The structure of the pittosporatobiraside was elucidated to be 12-angeloyloxy-6,14-dimethyl-2-methylene-9-(1-methylethyl)-15,17-dioxatricyclo[8.7.0.011,16]heptadec-5-en-13-one by physico-chemical methods. This is a new type of glycoside, i.e., 3-angeloyloxy-2,6-dideoxy- xylo-4-hexosulopyranoside, of a germacrane-type sesquiterpene alcohol.
Structure of Tetraamraonium Octamolybdobis(diaquacoiprate(II)) Hexahydrate
Authors: Ito Fumiyuki , Ozeki Tomoji , Ichida Hikaru , Miyamae Hiroshi , Sasaki Yukiyoshi
Published: July 2006

A novel type of heteropolymolybdate containing Cu(II) was obtained and its crystal structure was determined by X-ray diffraction method. In the structure, two CuO6 octahedra connect two adjacent Mo8O28 units ky corner-sharing to form an infinite chain. The CuO6 prolates along the chain. The axial Cu–O distances and equatrial ones are ca. 2.5 and 2.0 Å respectively, which shows a Jahn–Teller distortion.
EXAFS Study on Polynuclear Molybdenum and Tungsten Compounds
Authors: Miyanaga Takafumi , Matsubayashi Nobuyuki , Fukumoto Takao , Yokoi Kunihiko , Watanabe Iwao , Murata Katsuo , Ikeda Shigero
Published: July 2006

EXAFS (Extended X-ray Absorption Fine Structure) spectra were analyzed for various polynuclear molybdates and tungstates in order to examine the feasibility of this method for the structural study of complex polynuclear compounds. We found an unusual phenomenon that Mo–O peaks in Fourier transforms of Mo6O192− and PMo12O403− are hardly discernible while the corresponding tungstates give the W–O peaks clearly and normally.
Thermal Cross Linking of Polyallylamine Modified by Perfluoroacylation as Langmuir–Blodgett Films
Authors: Sekiya Akira , Tamura Masanori , Watanabe Masako , Ishida Hiroyasu
Published: July 2006

Thermogravimetry analysis of polyallylamine modified by perfluoroacylation showed that thermal cross linking occurred if less than 20% of the amino groups in polyallylamine were modified by perfluoroacylation. The Langmuir–Blodgett (LB) Z type films of these low modified polymers were prepared and cross linked LB films were successfully prepared by heating these films. Characterization of the cross linked LB films was attempted.
Preparation of 3A,6A-Anhydro-β-cyclodextrin and Its Taka Amylolysis
Authors: Fujita Kahee , Yamamura Hatsuo , Imoto Taiji , Tabushi Iwao
Published: July 2006

3A,6A-Anhydro-β-cyclodextrin was prepared by the reaction of 6-O-(p-tosyl)-β-cyclodextrin with aqueous alkali. This anhydrocyclodextrin was enzymatically hydrolyzed by Taka amylase to give 3″,6″-anhydromaltotetraose exclusively.
Photochemical Reaction of [4(4′-Alkoxybenzoyl)phenylmethyl]phosphonic Acids. Application to a Photo-degradable Surfactant
Authors: Okamoto Yoshiki , Yoshida Hidetoshi , Takamuku Setsuo
Published: July 2006

Upon UV-irradiation, the C–P bonds of [4(4′-alkoxybenzoyl)phenyl]methylphosphonic acids were cleaved in water (pH 12) to give 4-alkoxyphenyl p-tolyl ketones and orthophosphate in high efficiency. It was demonstrated that the acids can be used as photo-degradable surfactants.
Diastereofacial Control in the Reaction of Chiral α-Amino Ketones with Several Organometallics
Authors: Fujisawa Tamotsu , Funabora Makoto , Ukaji Yutaka , Sato Toshio
Published: July 2006

The addition reaction of organometallics to chiral α-amino ketones, prepared from α-halo ketones and (S)-2-methoxymethylpyrrolidine as a chiral auxiliary, gave different diastereomers of chiral amino alcohols depending on the difference of coordination ability of the metal used, i.e. organometallics such as Grignard reagent, organozinc, and cerium reagents preferred re-face attack, while organolithium compound attacked from si-face.
New Reversible Enhancement/Depression Phenomenon on Catalysis of Platinum Supported on One-Atomic Layer Niobium Oxide for Ethene Hydrogenation
Authors: Asakura Kiyotaka , Iwasawa Yasuhiro
Published: July 2006

While platinum supported on one-atomic layer Niobium oxide which was chemically attached on a silica surface did not exhibit an SMSI phenomenon unlike usual Nb2O5-supported Pt, the ethene hydrogenation activity of the catalyst reduced at 773 K was much higher than a SiO2-supported Pt catalyst. Another interesting feature is that the activity was reversibly enhanced or depressed as a function of pre-evacuation temperature.
A New Mode of Aromatic Substitution and Redox Reaction of Substituted Benzenes with Disulfide Dication: 1,5-Dithioniabicyclo[3.3.0] octane Bis(trifluoromethanesulfonate)
Authors: Fujihara Hisashi , Akaishi Ryouichi , Furukawa Naomichi
Published: July 2006

Disulfide dication was found to react with several aromatics to give either the substitution or redox products. The reaction mode depends remarkably on the oxidation potential of the aromatics.
Characterization of Ternary Copper(II) Complexes Containing Reduced PQQ (PQQH2) and Bipyridine or Terpyridine
Authors: Suzuki Shinnichiro , Sakurai Takeshi , Itoh Shinobu , Ohoshiro Yoshiki
Published: July 2006

The ternary copper(II) complex containing reduced coenzyme PQQ (PQQH2) and bipyridine or terpyridine was prepared and characterized by electronic absorption and electron paramagnetic resonance (EPR) spectroscopy. The structures of these complexes are quite similar to those of the corresponding ternary complexes containing PQQ (oxidized form), in which the binding of PQQ to Cu(II) through N(6) and COO−(7) groups has been proposed.
Iodination of Aromatic Ethers by Use of Benzyltrimethylammonium Dichloroiodate and Zinc Chloride
Authors: Kajigaeshi Shoji , Kakinami Takaaki , Moriwaki Masayuki , Watanabe Masakazu , Fujisaki Shizuo , Okamoto Tsuyoshi
Published: July 2006

The reaction of aromatic ethers with benzyltrimethylammonium dichloroiodate(1-) in acetic acid in the presence of zinc chloride at room temperature gave iodo-substituted aromatic ethers in good yields.
Photoinduced Masked-Formylation of Vinylsulfone Derivatives with 1,3-Dioxolane. Application to the Synthesis of 3,4-Disubstituted Pyrroles
Authors: Inomata Katsuhiko , Suhara Hiroshi , Kinoshita Hideki , Kotake Hiroshi
Published: July 2006

It was found that α-cyanovinylsulfones, which were prepared by an improved Knoevenagel condensation, react readily with 1,3-dioxolane under ultraviolet irradiation in the presence of a photosensitizer. The reaction provided a new convenient method for the preparation of 3,4-disubstituted pyrroles.
Molecular Orientation and Domain Formation in Surface Monolayers of Azobenzene-Containing Amphiphiles and Their Polyion Complexes
Authors: Kimizuka Nobuo , Kunitake Toyoki
Published: July 2006

Examination of the surface monolayer on pure water or on aqueous polyanion of two azobenzene-containing compounds by the pressure-area isotherm and absorption spectroscopy established the controlled formation of surface microcrystals, islands, liquid expanded films, and condensed films.
Total Synthesis of (+)-Validoxylamine A
Authors: Ogawa Seiichiro , Miyamoto Yasunobu
Published: July 2006

(+)-Validoxylamine A was synthesized by selective deoxygenation of (+)-validoxylamine B derivative, which was obtained by the coupling of the partially protected (+)-valienamine and (1R,2S,5R,7R,8R,9R,10R)-8,9-dibenzyloxy-5-phenyl-4,6,11-trioxatricyclo[8.1.0.02,7]undecane. The present synthesis constitutes a formal total synthesis of antibiotic validamycin A.
Reactivity of Cumulene Complexes. Two Competing Pathways in Oxidative Solvolysis of Tetramethylbutatriene(hexacarbonyl)diiron
Authors: Kiyooka Syun-ichi , Atagi Takuya , Fujiyama Ryoji , Isobe Kiyoshi
Published: July 2006

The oxidation of tetramethylbutatriene(hexacarbonyl)diiron in alcohols by eerie ammonium nitrite regioselectively gives diene-diesters and acetylene-diethers in moderate yields. The reaction is the first example showing that both the carbonylation and etherification of cumulene ligand with solvent alcohols take place concurrently on cationic 17-electron species.
Synthesis of (R)-(+)-4-Butyl-2,6-cycloheptadienone, a Constituent of Marine Algae
Authors: Asaoka Morio , Takenouchi Kazuya , Takei Hisashi
Published: July 2006

The title compound was synthesized from (R)-(−)-5-trimethylsilyl-2-cyclohexenone in 19% overall yield.
A Possible Model of Aromatic-Guest Recognition in Paracyclophane-Guest Inclusion Processes
Authors: Aoyama Norihito , Sakurai Minoru , Kitagawa Masaki , Inoue Yoshio , Chûjô Riichirô
Published: July 2006

On the basis of the MMP2 molecular mechanics calculations, a possible mechanism is proposed for aromatic-guest selectivity found in the formation of paracyclophane-guest inclusion complexes.
Synthesis of 2-Acetoxy-4-formylphenyl 2,3-Di-O-acetyl-6-deoxy-β-d-arabino-5-hexulofuranoside, Structure Confirmation of the Anomeric Configuration of Antibiotic Hygromycin A
Authors: Chida Noritaka , Ohtsuka Masami , Ogawa Seiichiro
Published: July 2006

2-Acetoxy-4-formylphenyl 2,3-di-O-acetyl-6-deoxy-β-d-arabino-5-hexulofuranoside, one of the degradation products of antibiotic hygromycin A, was synthesized. The present study confirmed the anomeric configuration of the antibiotic to be “β”.
A Convenient Method for the Transformation of Allylstannanes to Alcohols, Ethers, Esters, and Amines
Authors: Takeda Takeshi , Inoue Tomoya , Fujiwara Tooru
Published: July 2006

Allylstannanes were easily oxidized with copper(II) bromide in the presence of water, alcohols, and sodium acetate to give the corresponding allylic alcohols, ethers, and acetates, respectively. The allylic amines were also obtained by the successive treatments of allylstannanes with copper(II) bromide and amines.
Recognition–Adsorption of Artificial Liposomes onto Glass Surface Modified with Octadecylsilyl Monolayer
Authors: Yamamura Kazuo , Hatakeyama Hitoshi , Tabushi Iwao
Published: July 2006

Octadecylsilyl(ODS) modified glass support having R–NH2 in the template cavity on ODS, (H2N–R)y·ODS[SiO2], adsorbed negatively charged artificial liposomes, (X(i)/Lip·CL−), opening a way to a new unique supramolecular assembly system.
A Novel Fluorescent Tracer for Visualizing Coupled Cells in Neural Circuits of Living Tissue
Authors: Hoshi Hideo , O'Brien John , Mills Stephen L.
Published: July 2006

Gap junctions have diverse roles in a wide variety of tissues and have recently become a subject of intense investigation in neural circuits where synchrony and oscillations may play an important part. In circuits where gap junctions are present, the possibility arises of identifying intercommunicating cells via introduction of tracer into one cell and observing its spread into its coupled neighbors. Staining the coupled cells by this means opens the door to many vital techniques including paired-cell electrophysiology, RT-PCR, and morphological characterization of previously unknown coupled cells. Tracers commonly used at the present time are not generally suitable for these purposes in many tissues, including neurons. This paper describes how a fluorescent nuclear tracer, Po-pro-1, can be used to visualize coupled cells in several types of retinal neurons thought to be comprised of different connexin proteins including Cx36, Cx45, Cx50, and Cx57.
Three-dimensional Reconstruction of Fracture Callus Morphogenesis
Authors: Gerstenfeld Louis C. , Alkhiary Yaser M. , Krall Elizabeth A. , Nicholls Fred H. , Stapleton Stephanie N. , Fitch Jennifer L. , Bauer Megan , Kayal Rayyan , Graves Dana T. , Jepsen Karl J. , Einhorn Thomas A.
Published: July 2006

Rat and mouse femur and tibia fracture calluses were collected over various time increments of healing. Serial sections were produced at spatial segments across the fracture callus. Standard histological methods and in situ hybridization to col1a1 and col2a1 mRNAs were used to define areas of cartilage and bone formation as well as tissue areas undergoing remodeling. Computer-assisted reconstructions of histological sections were used to generate three-dimensional images of the spatial morphogenesis of the fracture calluses. Endochondral bone formation occurred in an asymmetrical manner in both the femur and tibia, with cartilage tissues seen primarily proximal or distal to the fractures in the respective calluses of these bones. Remodeling of the calcified cartilage proceeded from the edges of the callus inward toward the fracture producing an inner-supporting trabecular structure over which a thin outer cortical shell forms. These data suggest that the specific developmental mechanisms that control the asymmetrical pattern of endochondral bone formation in fracture healing recapitulated the original asymmetry of development of a given bone because femur and tibia grow predominantly from their respective distal and proximal physis. These data further show that remodeling of the calcified cartilage produces a trabecular bone structure unique to fracture healing that provides the rapid regain in weight-bearing capacity to the injured bone. (J Histochem Cytochem 54:1215-1228, 2006)
A questionnaire survey on the management of Graves’ orbitopathy in Europe
Authors: _ _ , Perros P , Baldeschi L , Boboridis K , Dickinson A J , Hullo A , Kahaly G J , Kendall-Taylor P , Krassas G E , Lane C M , Lazarus J H , Marcocci C , Marino M , Mourits M P , Nardi M , Orgiazzi J , Pinchera A , Pitz S , Prummel M F , Wiersinga W M
Published: July 2006

Objective: To determine management patterns among clinicians who treat patients with Graves’ orbitopathy (GO) in Europe.

Design and methods: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians.

Results: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P < 0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P < 0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P < 0.05) and surgical decompression (from 20.9 to 52.9%, P < 0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P < 0.01).

Conclusion: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.
Baseline characteristics and response to GH replacement of hypopituitary patients previously irradiated for pituitary adenoma or craniopharyngioma: data from the Pfizer International Metabolic Database
Authors: Maiter D , Abs R , Johannsson G , Scanlon M , Jönsson P J , Wilton P , Koltowska-Häggström M
Published: July 2006

Objective: To test the hypothesis whether the effects of GH replacement therapy in adults could be affected by prior pituitary irradiation, the baseline characteristics and response to GH were evaluated in adults with severe GH deficiency (GHD), who had received or not irradiation for the treatment of pituitary adenoma or craniopharyngioma.

Design: Data from 447 patients, who had received radiotherapy (427 in addition to surgery), and 630 patients, who were operated on but not irradiated for their tumour, were retrieved from Pfizer International Metabolic Database (KIMS) and compared at baseline and 1 and 2 years following the onset of GH replacement.

Results: Irradiated and non-irradiated patients exhibited the expected phenotype of GHD at baseline. However, irradiated patients had a greater impairment in the quality of life (QoL), a higher fat mass, lower high-density lipoprotein cholesterol levels and a lower bone mineral content (BMC) than non-irradiated patients. Treatment with GH induced similar changes in both groups. After 1 year of GH replacement, there was an increase in serum IGF-I and fat-free mass, a reduction in fat mass and an improvement in QoL, all changes being equivalent in irradiated and non-irradiated patients. The lipid profile also improved with the irradiated patients showing a better response. These beneficial effects were maintained and the BMC also increased in both groups by the second year of treatment.

Conclusions: This analysis shows that prior irradiation for pituitary adenoma or craniopharyngioma does not compromise the beneficial effects of GH replacement therapy.
Is ghrelin a signal of decreased fat-free mass in elderly subjects?
Authors: Bertoli S , Magni P , Krogh V , Ruscica M , Dozio E , Testolin G , Battezzati A
Published: July 2006

Objective: Aging is associated with appetite decline, weight loss, reduced fat-free mass (FFM), and increased fat mass (FM). Ghrelin and leptin are short- and long-term determinants of energy balance respectively, whose dysregulation could alter food intake. We evaluate the relationship of circulating ghrelin and leptin responses to standardized oral mixed nutrient load (SOMNL) with body composition, daily food intake, and insulin sensitivity in healthy elderly subjects (ES).

Design and methods: Twenty-six ES (12/14 M/F, 69±4 years) and ten young healthy controls (LY) (5/5 M/F, 27±3 years) were studied at the International Center for the Assessment of Nutritional Status (Milan, Italy) with air plethysmography, dual energy X-ray absorptiometry, indirect calorimetry, and dietary intake assessment. Basal and postprandial ghrelin, leptin, testosterone, glucose, insulin and C-peptide concentrations, and insulin resistance (homeostasis model assessment (HOMA-R)) and sensitivity (quantitative insulin-sensitivity check index (QUICKI)) were evaluated.

Results: Basal ghrelin levels were similar in ES and LY, whereas leptin was higher in ES than LY, in agreement with the higher amount of FM. Basal and percentage change in ghrelin were inversely related to FFM, appendicular skeletal muscle mass (SMM), and QUICKI, but not to FM. Basal and percentage change in leptin were directly related to FM and not to FFM indexes. Ghrelin basal concentration was negatively correlated with energy and protein intake and with QUICKI. Percentage change in Ghrelin after SOMNL correlated negatively with protein intake, but positively with resting energy expenditure and energy intake, and glucose, insulin, C-peptide basal concentrations, and HOMA-R.

Conclusion: In ES, basal and postprandial ghrelin increases with FFM, specifically SMM, reduction, whereas leptin increases with relative FM increases.
Effect of Food and Ranitidine on Saquinavir Pharmacokinetics and Gastric pH in Healthy Volunteers
Authors: Kakuda Thomas N. , Falcon Ronald W.
Published: July 2006

Study Objectives. To assess the relative bioavailability of saquinavir after administration with ranitidine alone, ranitidine and food, and food alone; and to investigate the mechanism underlying the effects of pH and food on saquinavir absorption.

Design. Single‐center, open‐label, randomized, three‐part crossover, pharmacokinetic pilot study.

Setting. General clinical research center in Scotland.

Subjects. Twelve healthy male volunteers.

Intervention. Each subject was given a single dose of saquinavir mesylate 600 mg with one of three randomly assigned treatments: ranitidine 150 mg on the evening before and 150 mg on the day of study drug administration, without food (treatment A); ranitidine 150 mg on the evening before and 150 mg on the day of study drug administration, with food (treatment B); and with food alone (treatment C, control). After a 7‐day washout period between each of the interventions, subjects received the other two treatments.

Measurements and Main Results. Blood samples were taken serially for 24 hours after each saquinavir dose, and gastric pH was measured during the 8 hours after dosing. Adverse events were monitored throughout the study. Single doses of saquinavir were well tolerated with or without ranitidine. Of the three treatments, the highest mean maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) for saquinavir occurred with treatment B; the lowest Cmax and AUC occurred with treatment A. Compared with treatment C (control), saquinavir's bioavailability was 15.9% (90% confidence interval [CI] 10–25%) after treatment A and 167% (90% CI 106–265%) after treatment B. Interindividual variability in both Cmax and AUC was slightly greater after treatments A and B than after treatment C. No correlation was found between pharmacokinetic parameters (Cmax and AUC) and gastric pH parameters, including maximum pH and pH at the time of drug delivery.

Conclusion. Plasma concentrations of saquinavir were significantly higher when the drug was administered with food and ranitidine than when it was given with food alone. However, these increases were not related to changes in gastric pH caused by ranitidine. It can be postulated that food does not increase the bioavailability of saquinavir through its effect on gastric pH.
Factors Affecting the Apparent Clearance of Tacrolimus in Korean Adult Liver Transplant Recipients
Authors: Lee Ju Yeun , Hahn Hyeon Joo , Son In Ja , Suh Kyung Suk , Yi Nam Joon , Oh Jung Mi , Shin Wan Gyoon
Published: July 2006

Study Objective. To identify the factors affecting tacrolimus apparent total body clearance (Cl/F [F = bioavailability]) in adult liver transplant recipients.

Design. Population pharmacokinetic analysis using data from a retrospective chart review.

Setting. University‐affiliated hospital in Seoul, South Korea.

Patients. Fifty‐one adult liver transplant recipients who had received tacrolimus after transplantation.

Measurements and Main Results. Data on 35 adult liver transplant recipients for model building and 16 patients for model validation were obtained retrospectively. Population average parameter estimates of Cl/F and apparent volume of distribution (V/F) were sought by using the nonlinear mixed‐effect model (NONMEM) program. A number of clinical covariates were screened for their influence on these pharmacokinetic parameters. The final optimal population model related Cl/F to total bilirubin, early (≤ 3 days) and late (> 35 days) postoperative days, international normalized ratio (INR), and graft:recipient weight ratio (GRWR). The NONMEM estimates indicated that the Cl/F of tacrolimus was decreased in patients with a small graft, hyperbilirubinemia, and a high INR. In addition, the Cl/F of tacrolimus almost doubled 4 days after transplantation, but decreased with an increase in duration of therapy after day 35. Mean prediction error and mean absolute prediction error were 0.26 and 3.78 ng/ml, respectively, for the validation sample. A final analysis in all 51 patients, which consisted of 1775 blood samples for concentration measurements, identified the following regression model: Cl/F (L/hr) = (0.36 + 2.01/POD • L) • TBIL−0.23 (TBIL = 1 if TBIL level ≤ 1.2 mg/dl, otherwise TBIL = TBIL level) • 0.49(if POD ≤ 3 days) • 0.75(if INR > 1.4) • 0.86(if GRWR ≤ 1.25%) • WT, where L was 1 if postoperative day (POD) was greater than 35 days, otherwise L was 0; V/F was 568 L, TBIL was total bilirubin, and WT was body weight. The interindividual variabilities (coefficients of variation) in Cl/F and V/F were 35.35% and 68.12%, respectively. The residual variability was 3.14 ng/ml.

Conclusion. These findings could be useful to the health care provider for adjustment of tacrolimus dosage in adult liver transplant recipients with various clinical factors.
Reversal of Elevated International Normalized Ratios and Bleeding with Low‐Dose Recombinant Activated Factor VII in Patients Receiving Warfarin
Authors: Dager William E. , King Jeff H. , Regalia Ron C. , Williamson Dean , Gosselin Robert C. , White Richard H. , Tharratt R. Steven , Albertson Timothy E.
Published: July 2006

Study Objective. To assess the effectiveness of using low‐dose recombinant activated factor VII (rFVIIa) to reverse the effects of warfarin in critically ill patients with major bleeding events.

Design. Prospective observational study.

Setting. Intensive care unit of a 500‐bed university‐affiliated hospital.

Patients. Sixteen nonhemophiliac patients who had been receiving warfarin and had an acute major bleeding event.

Intervention. Patients received rFVIIa 1.2 mg for reversal of anticoagulation.

Measurements and Main Results. Patients were identified from clinical pharmacology consult service electronic tracking records, and their data were cross‐checked with the pharmacy information system. Information collected for each patient included extent of bleeding and magnitude of elevation in international normalized ratio (INR). A mean ± SD dose of rFVIIa 16.3 ± 4.1 μg/kg (range 11–25 μg/kg) reduced the mean INR from 2.8 ± 1.6 (range 1.44–6.34) to 1.07 ± 0.27 (range 0.86–1.92, p<0.001). A rapid onset of response for achieving a desirable hemostatic effect was observed in 14 of the 16 patients.

Conclusion. Low‐dose rFVIIa appears to be an effective, rapid reversal modality for major bleeding events in the presence of warfarin and an elevated INR. The agent's response is quicker than that expected with fresh frozen plasma combined with vitamin K. In emergency situations, rFVIIa 1.2 mg can be used to reverse the anticoagulant effect of warfarin and other vitamin K antagonists without inducing a hypercoagulable state; the product, however, is expensive.
Tigecycline: First of a New Class of Antimicrobial Agents
Authors: Rose Warren E. , Rybak Michael J.
Published: July 2006

Tigecycline is the first commercially available member of the glycylcyclines, a new class of antimicrobial agents. The glycylcyclines are derivatives of the tetracycline antibiotics, with structural modifications that allow for potent gram‐positive, gram‐negative, and anaerobic activity, including certain multidrug‐resistant strains. The enhanced activity can be attributed to stronger binding affinity and enhanced protection against several mechanisms of resistance that affect other antibiotic classes such as tetracyclines. Tigecycline exhibits generally bacteriostatic action by reversibly binding to the 30S ribosomal subunit and inhibiting protein translation. In vitro activity has been demonstrated against multidrug‐resistant gram‐positive pathogens including methicillin‐resistant and glycopeptide‐intermediate and ‐resistant Staphylococcus aureus, as well as vancomycin‐resistant enterococci. Multidrug‐resistant gram‐negative pathogens, such as Acinetobacter baumannii and extended‐spectrum β‐lactamase–producing Klebsiella pneumoniae and Escherichia coli, are typically highly susceptible to tigecycline. The drug also has displayed significant activity against many clinically important anaerobic organisms. This agent demonstrates a predictable pharmacokinetic profile and minimal drug interactions, and is generally well tolerated, with nausea being the most common adverse event. It was approved in June 2005 for the treatment of complicated skin and skin structure infections (SSSIs) and complicated intraabdominal infections. Currently, a limited number of broad‐spectrum antimicrobials are available to combat multidrug‐resistant organisms. The addition of new agents is essential to limiting the spread of these pathogens and improving outcomes in patients with these types of infections. Tigecycline has demonstrated promising results in initial in vitro and clinical studies for SSSIs and complicated intraabdominal infections; however, further clinical experience will clarify its role as a broad‐spectrum agent.
Olanzapine‐Associated Neuroleptic Malignant Syndrome
Authors: Norgard Nick B. , Stark Jennifer E.
Published: July 2006

Neuroleptic malignant syndrome (NMS) is a rare but potentially serious complication of neuroleptic drugs. It may vary in both presenting characteristics and severity. Several different criteria for diagnosis exist, and each differs from the others slightly. We describe a 66‐year‐old woman with chronic paranoid schizophrenia who was prescribed olanzapine along with several other psychiatric drugs and an antihypertensive drug. The patient displayed several characteristics of NMS during therapy with olanzapine, including fever, elevated creatine kinase level, leukocytosis, and mild muscle rigidity. When olanzapine was held, the signs and symptoms improved and then returned with rechallenge of olanzapine. For this reason, olanzapine was considered strongly associated with this patient's apparent NMS episode. The patient's β‐blocker therapy may have masked additional signs of NMS. In addition, the patient tolerated other neuroleptics that were started in the hospital after the suspected NMS episode. The variation among different diagnostic criteria makes this syndrome a challenging diagnosis at times, in particular when atypical antipsychotics are suspected as the causative agent.
Geography versus brands in a global wine market
Authors: Schamel Günter
Published: July 2006

Producer brands increasingly dominate global wine markets, while generic advertising promotes regionality and exports (e.g., Australia, Spain). We analyze U.S. price data and quality indicators for 24 wine regions within 11 countries using a hedonic model. We assess the value of producer brands vs. geographical indicators, defining an indicator for high, average, and low quality producers (brands) within a region based on relative peer performance, i.e., whether they consistently produce qualities above or below their regional average. In contrast to high quality producers from France and Italy, their counterparts from the New World never exceed prices for high quality Napa Valley brands. Thus, New World wine still has to catch up with the Old World in terms of regional reputation, but leading brands are able to pick up much of the price differential. Generic promotions, export quality controls, and regional quality leaders emphasizing origin in their own marketing may level the playing field for laggard regions. [EconLit citations: D400, Q130, L140]. © 2006 Wiley Periodicals, Inc. Agribusiness 22: 363–374, 2006.
A peptide from thrombospondin 1 modulates experimental erosive arthritis by regulating connective tissue growth factor
Authors: Manns Joanne M. , Uknis Audrey B. , Rico Mario C. , Agelan Alexis , Castaneda Julian , Arango Israel , Barbe Mary F. , Safadi Fayez F. , Popoff Steven N. , DeLa Cadena Raul A.
Published: July 2006

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with leukocyte adhesion to and extravasation through vascular endothelium into synovial tissue. Recent evidence indicates that the thrombospondin 1 gene is up‐regulated in patients with RA. We have identified a region within the TSP‐1 type 3 repeats that inhibits human neutrophil elastase (HNE) and binds to human neutrophils. The present study was undertaken to investigate the therapeutic benefit of this TSP‐1–derived peptide sequence and its effect on connective tissue growth factor (CTGF), a protein involved in fibrotic disorders and in neovascularization, which is a hallmark of RA.

Methods

CTGF gene and protein expression, as well as protein levels of CTGF in the synovium, after treatment with the TSP‐1–derived peptide were studied in the peptidoglycan–polysaccharide animal model of erosive arthritis.

Results

Peptide treatment prevented joint infiltration and inflammation and was associated with reduced circulating antigen levels of HNE and TSP‐1. Additionally, CTGF was up‐regulated in this experimental model of RA. Treatment with the TSP‐1–derived peptide was associated with down‐regulation of the message and protein levels of CTGF. Immunofluorescence studies showed that the mean area fraction of CTGF immunoreactivity in the peptide‐treated group of animals was significantly less than that in the untreated group.

Conclusion

These results document a role for TSP‐1 in regulating CTGF gene and protein expression in synovial tissue, suggesting a link with the disease course in this model of RA. This TSP‐1–derived synthetic peptide may represent an important template for drug development in RA and other inflammatory conditions associated with neutrophil activation.
Bone marrow endothelial progenitors are defective in systemic sclerosis
Authors: Papa Nicoletta Del , Quirici Nadia , Soligo Davide , Scavullo Cinzia , Cortiana Michela , Borsotti Chiara , Maglione Wanda , Comina Denise P. , Vitali Claudio , Fraticelli Paolo , Gabrielli Armando , Cortelezzi Agostino , Lambertenghi‐Deliliers Giorgio
Published: July 2006

Objective

Vascular abnormalities represent the main component of the pathobiology of systemic sclerosis (SSc), progressing from structural derangements of the microcirculation with abortive neoangiogenesis to final vessel loss. Since circulating endothelial progenitor cells (EPCs) are important in the vascular repair process, we undertook this study to examine their numbers in the peripheral blood (PB) of SSc patients and to evaluate whether their status is related to impaired quantitative and/or qualitative aspects of the bone marrow (BM) microenvironment.

Methods

Circulating EPCs from 62 SSc patients were evaluated by flow cytometry and characterized as CD45 negative and CD133 positive. BM EPCs, identified as CD133 positive, were isolated from 14 SSc patients and grown to induce endothelial differentiation. In addition, progenitor numbers and functional properties of hematopoietic and stromal compartments were analyzed by various assays.

Results

We found that EPCs were detectable in the PB of patients with SSc, and their number was significantly increased in patients with early‐stage disease but not in those with late‐stage disease. All of the examined BM samples contained reduced numbers of EPCs and stromal cells, both of which were functionally impaired. Both endothelial and stromal progenitors expressed vascular endothelial growth factor receptor, indicating that BM is strongly induced to differentiate into the endothelial lineage; furthermore, only BM EPCs from patients with early disease led to endothelial differentiation in vitro.

Conclusion

This study provides the first demonstration that in SSc, there is a complex impairment in the BM microenvironment involving both the endothelial and mesenchymal stem cell compartments and that this impairment might play a role in defective vasculogenesis in scleroderma.
Effect of crowding by dextrans and Ficolls on the rate of alkaline phosphatase–catalyzed hydrolysis: A size‐dependent investigation
Authors: Homchaudhuri L. , Sarma Navanita , Swaminathan Rajaram
Published: July 2006

The cell cytosol is crowded with macromolecules such as proteins, nucleic acids, and membranes. The consequences of such crowding remain unclear. How is the rate of a typical enzymatic reaction, involving a freely diffusing enzyme and substrate, affected by the presence of macromolecules of different sizes, shapes, and concentrations? Here, we mimic the cytosolic crowding in vitro, using dextrans and Ficolls, for the first time in a variety of sizes ranging from 15 to 500 kDa, in a concentration range 0–30% w/w. Alkaline phosphatase–catalyzed hydrolysis of p‐nitrophenyl phosphate (PNPP) was chosen as the model reaction. A pronounced decrease in the rate with increase in fractional volume occupancy of dextran is observed for larger dextrans (200 and 500 kDa) in contrast to smaller dextrans (15–70 kDa). Our results indicate that, at 20% w/w, smaller dextrans (15–70 kDa) reduce the initial rate moderately (1.4‐ to 2.4‐fold slowing), while larger dextrans (>200 kDa) slow the reaction considerably (>5‐fold). Ficolls (70 and 400 kDa) slow the reaction moderately (1.3‐ to 2.3‐fold). The influence of smaller dextrans was accounted by a combination of increase in viscosity as sensed by PNPP and a minor offsetting increase in enzyme activity due to crowding. Larger dextrans apparently reduce the frequency of enzyme substrate encounter. The reduced influence of Ficolls is attributed to their compact and quasispherical shape, much unlike the dextrans. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 477–486, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The effect of heat shock on paclitaxel production in Taxus yunnanensis cell suspension cultures: Role of abscisic acid pretreatment
Authors: Zhang Changhe , Fevereiro Pedro S.
Published: July 2006

The heat shock (HS) response is a conserved cellular defense mechanism to elevated temperatures, observed in cells from bacteria to human. It is characterized by the increased accumulation of HS proteins. This work examines the effect of HS on the secondary metabolite biosynthesis of cultured plant cells. Suspension cultures of Taxus yunnanensis cells, which produce the anticancer diterpenoid paclitaxel (Taxol®), were heat shocked at 35–50°C for 30–60 min. The results show that HS reduced cell viability and growth but significantly induced paclitaxel production. The HS‐induced paclitaxel production depended on the intensity of HS and the physiological state of the cells. Abscisic acid (ABA)‐pretreatment not only increased cell viability and growth upon HS but also improved HS‐induced paclitaxel yield. The best culture phase to apply the HS was the late‐exponential growth phase. Under the optimized condition, HS enhanced paclitaxel yield by sixfold to 6.8 mg/L. In addition, a prior mild‐HS treatment also significantly increased HS‐induced paclitaxel production. Furthermore, HS induced oxidative burst, the early event of plant defense response to pathogen attack and other stress challenge; the addition of putative inhibitors of lipoxygenase, a key enzyme for jasmonic acid biosynthesis, significantly inhibited HS‐induced pacliatxel accumulation. The stimulation of secondary metabolite production by HS may be a result of HS‐induced plant cell defense response. Biotechnol. Bioeng. 2007;96: 506–514. © 2006 Wiley Periodicals, Inc.
Azanonaboranes Containing Imidazole Derivatives for Boron Neutron Capture Therapy: Synthesis, Characterization, and In Vitro Toxicity Evaluation
Authors: El‐Zaria Mohamed E. , Genady Afaf R. , Gabel Detlef
Published: July 2006

A number of azanonaboranes containing imidazole derivatives have been synthesized by a ligand‐exchange reaction. The exo‐NH2R group of the azanonaborane of the type [(RH2N)B8H11NHR] can be exchanged by one hetero‐nitrogen atom of the imidazole ring. In the case of histamine, the exchange takes place on the aliphatic amino group, the hetero‐nitrogen atom of the imidazole ring or both of them. The products were confirmed by NMR, IR spectroscopy, elemental analysis, and mass spectrometry. The electron‐withdrawing effect of the nitro group in 2‐nitroimidazole is the main hindrance to achieve the exchange reaction. In vitro experiments were performed with B16 melanoma cells. A comparison of the biological properties of the products in which the B8N cluster is connected to the hetero‐nitrogen atom of imidazole ring or the aliphatic NH2 group showed that incorporation of B8N cluster unit into primary amino group increases the compound's toxicity. In contrast, this specificity for cytotoxicity effect was not observed in the case of histamine containing two B8N clusters which was relatively nontoxic and did not inhibit colony formation up to concentrations of 2 mM.
Structures and Electronic Absorption Spectra of a Recently Synthesised Class of Photodynamic Therapy Agents
Authors: Quartarolo Angelo Domenico , Russo Nino , Sicilia Emilia
Published: July 2006

A theoretical study was performed on a novel class of boron‐containing molecules (various substituted tetraarylazadipyrromethenes), which show in vitro activity for application in photodynamic therapy. Geometric optimisation of the structures for the singlet and triplet electronic states was carried out on compounds in vacuo at the density functional level of theory, by employing the PBE0 hybrid functional and the split‐valence plus polarisation basis set. The absorbance properties in the UV‐visible region were examined by means of time‐dependent density functional response theory, using the same functional as mentioned above. To evaluate the influence of the solvent on the excitation energies, the continuum polarisable model was applied. Calculated electronic excitations, such as those regarding the Q‐like band, were found to be in good agreement (within 0.01–0.1 eV) with experimental values and experimental trends on changing both the substituents and solvent.
Response to low‐dose ketoconazole and subsequent dose escalation to high‐dose ketoconazole in patients with androgen‐independent prostate cancer
Authors: Nakabayashi Mari , Xie Wanling , Regan Meredith M. , Jackman David M. , Kantoff Philip W. , Oh William K.
Published: July 2006

BACKGROUND.

High‐dose ketoconazole (HDK) in combination with steroids has been recognized as an effective secondary hormonal therapy in androgen‐independent prostate cancer (AIPC). However, HDK causes more severe adverse events than low‐dose ketoconazole (LDK). To the authors' knowledge, relatively little is known regarding the efficacy of LDK in AIPC. The efficacy of LDK and of subsequent dose escalation from LDK to HDK was evaluated as secondary hormonal therapy in patients with AIPC.

METHODS.

In a single institution, patients with AIPC treated with LDK (at a dose of 200 mg orally 3 times daily) as secondary hormonal therapy with or without concomitant steroids were retrospectively identified. In addition, patients were identified who received dose escalation to HDK (400 mg orally 3 times daily) after experiencing a rising prostate‐specific antigen (PSA) level.

RESULTS.

Thirty‐nine of 138 eligible patients (28.3%, 95% confidence interval [95% CI], 20.9–36.6%) treated with LDK experienced PSA declines ≥50%. The median time to disease progression or dose escalation on LDK was 3.2 months (range, 0.1+–61 months). Dose escalation to HDK was subsequently performed in 55 patients (39.9%), 7 of whom (12.7%) demonstrated a subsequent PSA decline ≥50%. A longer duration of primary androgen deprivation therapy and total duration of all previous hormonal therapies was associated with a longer time to progression with LDK (P < .05). The most common reversible adverse effect of LDK was NCI Common Toxicity Criteria Grade 1 or 2 fatigue (12.3%).

CONCLUSIONS.

LDK is associated with a PSA response rate comparable to HDK as secondary hormonal therapy in patients with AIPC, but with less toxicity. Although uncommon, additional durable responses occurred in some patients after dose escalation. Cancer 2006. © 2006 American Cancer Society.