Identification of stable cytotoxic factors in the gas phase extract of cigarette smoke and pharmacological characterization of their cytotoxicity.

Smoking is a major risk factor for atherosclerotic vascular diseases, but the mechanism for its genesis is unknown. We have recently shown that the gas phase of cigarette smoke (nicotine- and tar-free cigarette smoke extract; CSE) likely to reach the systemic circulation contains stable substances which cause cytotoxicity like plasma membrane damage and cell death in cultured cells, and also that the plasma membrane damage is caused through sequential activation of protein kinase C (PKC) and NADPH oxidase (NOX) and the resulting generation of reactive oxygen species (PKC/NOX-dependent mechanism), whereas cell death is caused through PKC/NOX-dependent and -independent mechanisms. To identify these stable substances, the CSE was prepared by passing the main-stream smoke of 10 cigarettes through a Cambridge glass fiber filter, trapping of the smoke in a vessel cooled at -80°C, and subsequent dissolution in 10ml of water.

In vitro and in vivo evaluations of a radioiodinated thymidine phosphorylase inhibitor as a tumor diagnostic agent for angiogenic enzyme imaging.

Introduction: The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis, tumor invasiveness and activation of antitumor agents. We evaluated radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ([(125)I]IIMU) having high TP-inhibitory potency as the new radiotracer for SPECT targeting of TP expression in tumors.

Methods: The characteristics of the radioiodinated TP inhibitor IIMU were determined by evaluating the uptake by tumor cells in vitro and by biodistribution studies in vivo.

Synthesis and evaluation of a radioiodinated lumiracoxib derivative for the imaging of cyclooxygenase-2 expression.

Introduction: Despite extensive attempts to develop cyclooxygenase (COX)-2 imaging radiotracers, no suitable positron emission tomography (PET)/single photon emission computed tomography (SPECT) tracers are currently available for in vivo imaging of COX-2 expression. The aims of this study were to synthesize and evaluate a radioiodinated derivative of lumiracoxib, 2-[(2-fluoro-6-iodophenyl)-amino]-5-methylphenylacetic acid (FIMA), which is structurally distinct from other drugs in the class and has weakly acidic properties, as a SPECT tracer for imaging COX-2 expression.

Methods: The COX inhibitory potency was assessed by measuring COX-catalyzed oxidation with hydrogen peroxide.

Synthesis of a new NIR fluorescent Nd complex labeling agent.

Fluorescent analysis has been widely used in biological, chemical and analytical research. A useful fluorescent labeling agent should include NIR emission, a large Stoke's shift, and good labeling ability without interfering with the pharmacological profile of the labeled compound. Thus, we planned to develop an M-AMF-DOTA(Nd) derivative composed of an NIR fluorescent moiety and a maleimide conjugating moiety as a new NIR fluorescent labeling agent which fulfills these requirements.

An experimental approach to study the biosynthesis of brominated metabolites by the red algal genus Laurencia.

The production of labeled brominated metabolites with radioactive (82)Br in Laurencia species was investigated as part of a study of the biosynthesis of halogenated metabolites from species belonging to the red algal genus Laurencia (Rhodomelaceae, Ceramiales). Radiobromide [(82)Br], thin-layer chromatography (TLC), and TLC-autoradioluminography (ARLG) were used. When cultured in artificial seawater medium (ASP(12)NTA including Na(82)Br) under 16:8 h light:dark (LD) illumination cycles for 24 h, each of the strains of Laurencia, Laurencia japonensis Abe et Masuda, Laurencia nipponica Yamada (laurencin-producing race and laureatin-producing race), and Laurencia okamurae Yamada, produced species- (or race-) specific (82)Br-containing metabolites.

Isolation and identification of new vasodilative substances in diesel exhaust particles.

Background, Aim, And Scope: We recently developed a new isolation method for diesel exhaust particles (DEP), involving successive extraction with H(2)O, sodium bicarbonate, and sodium hydroxide, in which the sodium hydroxide extract was found to consist of phenolic components. Analysis of the extract revealed that vasodilative-active nitrophenols are in DEP in significantly higher concentrations than those estimated by an earlier method involving a combination of solvent extraction and repeated chromatography. These findings indicated that our new procedure offers a simple, efficient, and reliable method for the isolation and identification of bioactive substances in DEP.

NIR fluorescent ytterbium compound for in vivo fluorescence molecular imaging.

We have developed a new NIR fluorescent probe based on an ytterbium(III) (E)-1-(pyridin-2-yl-diazenyl)naphthalen-2-ol (PAN) complex. This probe emits near-infrared luminescence derived from the Yb ion through excitation of the PAN moiety with visible light (lambda(ex)= 530 nm, lambda(em)= 975 nm). The results support the possible utility of the probe for in vivo fluorescence molecular imaging.

Improvement of an efficient separation method for chemicals in diesel exhaust particles: analysis for nitrophenols.

Goal, Scope, And Background: Diesel exhaust is believed to consist of thousands of organic constituents and is a major cause of urban pollution. We recently reported that a systematic separation procedure involving successive solvent extractions, followed by repeated column chromatography, resulted in the isolation of vasodilatory active nitrophenols. These findings indicated that the estimation of the amount of nitrophenols in the environment is important to evaluate their effect on human health.

Usefulness of 11C-methionine for differentiating tumors from granulomas in experimental rat models: a comparison with 18F-FDG and 18F-FLT.

Unlabelled: Many clinical PET studies have shown that increased (18)F-FDG uptake is not specific to malignant tumors. (18)F-FDG is also taken up in inflammatory lesions, particularly in granulomatous lesions such as sarcoidosis or active inflammatory processes after chemoradiotherapy, making it difficult to differentiate malignant tumors from benign lesions, and is the main source of false-positive (18)F-FDG PET findings in oncology. These problems may be overcome by multitracer studies using 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) or l-(11)C-methionine.

Extensive FDG uptake and its modification with corticosteroid in a granuloma rat model: an experimental study for differentiating granuloma from tumors.

Introduction: Increased (18)F-fluorodeoxyglucose (FDG) uptake in inflammatory lesions, particularly in granulomatous inflammation (e.g., sarcoidosis), makes it difficult to differentiate malignant tumors from benign lesions and is the main source of false-positive FDG-PET findings in oncology.

A novel and efficient synthesis of [2-11C]5-fluorouracil for prognosis of cancer chemotherapy.

Purpose: In order to facilitate the use of the PET-based Strauss test for 5-FU sensitivity, a rapid and facile synthesis of [2-11C]5-fluorouracil ([2-11C]5-FU), based on = [11C]phosgene ([11C]COCl2), is reported.

Method: The key intermediate (E)-beta- benzoylamino-Alpha-fluoroacrylamide (1) and [11C]phosgene was submitted to cyclocondensation to give [2-11C]5-fluorouracil.

Results: [2-11C]5-Fluorouracil was synthesized in 17 min with high (25%) radiochemical yield.

Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as potential SPECT tracers for cyclooxygenase-2 expression.

Unlabelled: Although several COX-2 inhibitors have recently been radiolabeled, their potential for imaging COX-2 expression remains unclear. In particular, the sulfonamide moiety of COX-2 inhibitors may cause slow blood clearance of the radiotracer, due to its affinity for carbonic anhydrase (CA) in erythrocytes. Thus, we designed a methyl sulfone-type analogue, 5-(4-iodophenyl)-1-[4-(methylsulfonyl)phenyl]-3-trifluoromethyl-1H-pyrazole (IMTP).

Separation and characterization of alkyltrimethylbenzene derivatives in diesel exhaust particles (DEP).

In our continuing studies on estrogenic compounds in diesel exhaust particles (DEP), we have reported the systematic separation of alkyldibenzothiophenes from the estrogenic hexane fraction of DEP. In this study, another estrogenic fraction was further isolated and characterized. DEP were roughly fractionated by successive extraction with hexane, benzene, dichloromethane, methanol, 1 M ammonia and 1 M HCl.

Stereoselective synthesis of tetrahydronaphthocyclobuta[1,2-d]pyrimidinediones from 5-fluoro-1,3-dimethyluracil and naphthalenes.

Upon UV-irradiation in the presence of piperylene, 5-fluoro-1,3-dimethyluracil (5-FDMU) couples with naphthalenes having either an electron-withdrawing group or an electron-donating group by way of 1,2-cycloaddition via mode selectivity to give the corresponding naphthocyclobutapyrimidines regio- and stereo-selectively.

(2S)-2-[1-(2,4-Difluoro-5-iodophenyl)-2-deoxy-beta-D-ribofuranos-5-yloxy]-8-methyl-4H-1,3,2-benzodioxaphosphole 2-oxide.

The title compound, C(19)H(18)F(2)IO(6)P, prepared as a potential antiviral and anticancer agent from 3-methylsalicylchlorophosphane and 1-(2,4-difluoro-5-iodophenyl)-2-deoxy-beta-D-ribofuranose, is one of a 1:1 mixture of two diastereomers. The diastereomers differ in their configuration, S or R, at the asymmetric phosphorus center. X-Ray crystallographic analysis of the title compound has determined the absolute configuration at the asymmetric P center to be S.

Estrogenic and anti-androgenic activity of nitrophenols in diesel exhaust particles (DEP).

We recently isolated 4-nitrophenol, 2-methyl-4-nitrophenol, 3-methyl-4-nitrophenol, and 4-nitro-3-phenylphenol from diesel exhaust particles (DEP) and identified them as vasodilators. Because these compounds are alkylphenolic derivatives that might mimic hormones, we evaluated their estrogenic activity by human estrogen receptor (hER)-yeast screen assay. All of these nitrophenol derivatives except 2-methyl-4-nitrophenol exhibited estrogenic activity.

Synthesis and antiviral activity of novel fluorinated 2',3'-dideoxynucleosides.

A series of 5-(trifluoroethoxymethyl)-2',3'-dideoxyuridines and 5-[bis(trifluoroethoxy)-methyl]-2',3'-dideoxyuridines have been prepared and screened for antiviral activity. The conformations of these compounds are discussed on the bases of NOE studies and the MO calculations. Modelling and NOE studies suggest both syn- and anti conformations for these 5-(2,2,2-trifluoroethoxymethyl)- and 5-[bis(2,2,2-trifluoroethoxy)-methyl]- derivatives.

Characteristic brain distribution of 1-(14)C-octanoate in a rat model of focal cerebral ischemia in comparison with those of (123)I-IMP and (123)I-iomazenil.

Unlabelled: 1-(11)C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-(11)C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-(14)C-octanoate and compared it with N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) distribution (cerebral blood flow), (123)I-iomazenil ((123)I-IMZ) distribution (neuronal viability based on (123)I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia.

Methods: The right middle cerebral artery of each rat was occluded intraluminally.

Synthesis of 1-beta-D-(5-deoxy-5-iodoarabinofuranosyl)-2-nitroimidazole (beta-IAZA): a novel marker of tissue hypoxia.

The present work describes the synthesis of the beta-isomer of 1-alpha-D-(5-deoxy-5-iodoarabinofuranosyl)-2-nitroimidazole (IAZA). Radioiodinated IAZA ((123)I-IAZA) has been extensively studied as a radiopharmaceutical for the diagnosis of regional and/or focal tissue hypoxia in a variety of clinical pathologies. The beta-anomer of IAZA, 1-beta-D-(5-deoxy-5-iodoarabinofuranosyl)-2-nitroimidazole (beta-IAZA, 1), was synthesized via an unconventional route starting from 1-beta-D-(ribofuranosyl)-2-nitroimidazole (AZR), with a change of configuration at the C-2'-position to afford 1-beta-D-(arabinofuranosyl)-2-nitroimidazole (beta-AZA, 7).

Isolation of nitrophenols from diesel exhaust particles (DEP) as vasodilatation compounds.

The compounds in diesel exhaust particles (DEP) that are responsible for vasodilatation were isolated and characterized for the first time. From benzene extract of DEP, 2-methyl-4-nitrophenol, 3-methyl-4-nitrophenl and 4-nitrophenol were isolated, and their vasodilatation activities were confirmed. 3-methyl-4-nitrophenol caused dilatation of rat thoracic artery, and the other two nitrophenols, also showed vasodilatation activities.

Guaiacylglycerol-7'-O-methyl 8'-vanillic acid ether and related compounds from Boreava orientalis.

The threo and erythro forms of guaiacylglycerol-7'-O-methyl 8'-vanillic acid ethers, threo and erythro guaiacylglycerol 8'-vanillin ethers, and threo guaiacylglycerol 8'-(4-hydroxymethyl-2-methoxyphenyl) ether have been isolated from fruits of Boreava orientalis. Structural determinations were made on the basis of UV, MS, 1H- and 13C-NMR spectral data, including two-dimensional shift correlation. The relative configurations were assigned on the basis of 1H-NMR chemical shifts.

Separation and identification of Taxifolin 3-O-glucoside isomers from Chamaecyparis obtusa (Cupressaceae).

Taxifolin 3-O-glucoside isomers, [(2R, 3R)-, (2R, 3S)-, (2S, 3R)- and (2S, 3S)-] were isolated from leaves of Chamaecyparis obtuse (Cupressaceae). Their structures were elucidated on the basis of UV, MS, CD, 1H- and 13C-NMR spectral data, including 2D shift correlation. It was found that the compounds could be distinguished by the use of 1H- and 13C-NMR spectral data.

Increased [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) yield with recycled target [18O]water: factors affecting the [18F]FDG yield.

The reuse of [18O] water after being purified by distillation has been reported to give lower [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) yields, probably due to the presence of organic impurities. In our routine production of [18F]FDG, however, we observed increased [18F]FDG yields with recycled [18O]water. Thus, factors affecting [18F]FDG yield were examined using as-purchased (virgin) and recycled (by photochemical combustion and distillation) [18O]water.

Photoinduced transannular reaction of 1,3-dimethylcyclooctapyrimidine-2,4-diones.

This article reports further elaboration of the authors' investigations on the acid-catalyzed photorearrangements undergone by derivatives of 1,3-dimethylcyclooctapyrimidine-2,4-dione. In this case the results are represented for compounds containing a simple methyl or fluorine substituent at different positions in the eight-membered ring. Upon photolysis in frozen benzene containing trifluoroacetic acid, the monomethylated compounds give varying yields of pentalenopyrimidinedione products that are not generated from the fluorinated compounds, which are either inert or undergo hydration accompanied by dehyrofluorination.

A simplified and improved synthesis of [11C]phosgene with iron and iron (III) oxide.

[11C]Phosgene ([11C]COCl2), a useful precursor for labeling several radiopharmaceuticals, is generally produced by catalytic oxidation of [11C]carbon tetrachloride over Fe granules, although in low yields or with poor reproducibility. In order to develop am improved synthesis of [11C]phosgene, two oxidizing agents, Fe2O3 and CuO, were examined. The yield of [11C]phosgene was significantly increased using Fe2O3 powder mixed with Fe granules, while the use of CuO alone, or CuO powder mixed with Fe granules resulted in an insignificant yield.