Calcipotriol and betamethasone dipropionate synergistically enhances the balance between regulatory and proinflammatory T cells in a murine psoriasis model.

A topical medication combining calcipotriol (Cal) and betamethasone dipropionate (BDP) has proven effective in a number of randomized controlled trials performed in patients with psoriasis, but its mechanism of action has not been fully elucidated. We investigated whether the combination of Cal and BDP (Cal/BDP) in this topical medication had a synergistic effect on psoriasis-like dermatitis and explored the underlying immunological mechanisms in a murine psoriasis model induced by application of imiquimod. Cal/BDP synergistically inhibited ear thickening induced by imiquimod compared to monotherapy with either Cal or BDP.

Low systemic exposure and calcemic effect of calcipotriol/betamethasone ointment in rats with imiquimod-induced psoriasis-like dermatitis.

Vitamin D (VD) analogues-containing ointments are known to occasionally cause hypercalcemia in psoriasis patients, and the frequency of hypercalcemia is suggested to vary based on the VD analogue used. In this study, to address the differences in calcemic effects of VD-containing ointments, the calcemic effects of marketed VD-containing ointments, including calcipotriol (Cal), maxacalcitol (Max), tacalcitol (Tac), calcipotriol/betamethasone dipropionate (Cal/BDP) and maxacalcitol/betamethasone butyrate propionate (Max/BBP) ointments, were evaluated in a rat model of imiquimod-induced dermatitis. The topical application of Tac, Max and Max/BBP ointments, but not Cal and Cal/BDP ointments, to the imiquimod-induced skin lesions significantly induced an increase in the serum calcium level compared with the vaseline-treated group.

Olopatadine hydrochloride suppresses hot flashes induced by topical treatment with tacrolimus ointment in rats.

Tacrolimus ointment is prescribed for patients with atopic dermatitis, although it is known to cause transient burning sensations and hot flashes in the applied skin. The aim of this study was to evaluate the effects of olopatadine hydrochloride (olopatadine), an antiallergic agent with a histamine H1 receptor (H1R) antagonistic activity, on the incidence of hot flashes induced by topical treatment with tacrolimus ointment in rats. Consequently, the skin temperature was increased by the topical application of tacrolimus ointment in rats, and the rise in skin temperature was inhibited by pretreatment with olopatadine in a dose-dependent manner.

Fluorescence response of 3-trifluoroacetylaminophthalimide to a Li(+)-I(-) ion pair induced by 254 nm photolysis in acetonitrile.

A 3-trifluoroacetylaminophthalimide selectively distinguished LiI from other alkaline-metal iodides and lithium halides by a marked fluorescence colour change, from orange-yellow to sky-blue, subsequent to 254 nm photolysis.

Phthalide-derived novel fluoroionophores incorporating picolylamino receptors: synthesis and response to metal cations.

Phthalide derivatives incorporating mono- and di-picolylamino functionalities at the 6-position have been prepared as novel fluoroionophores and their fluorescence responses to metal cations have been investigated. These phthalides not only exhibited efficient fluorescence in an aqueous medium but also displayed fluorescence on-off response upon addition of transition-metal cations, namely Cu(2+). The 6-aminophthalide fluorophore served as the core of the fluorescent probes although it has rarely been applied to a chemosensor.

Facile synthesis of picene from 1,2-di(1-naphthyl)ethane by 9-fluorenone-sensitized photolysis.

A facile formation of picene was achieved by photosensitization of 1,2-di(1-naphthyl)ethane using 9-fluorenone as a sensitizer. This sensitized photoreaction is the first photochemical cyclization of ethylene-bridged naphthalene moieties to afford the picene skeleton. 5,8-Dibromopicene, prepared by this procedure using 1,2-di[1-(4-bromonaphthyl)]ethane as the substrate, was readily converted to novel functionalized picenes by conventional substitution and cross-coupling reactions.

Key physiological phenomena governing transgene expression based on tissue pressure-mediated transfection in mice.

It is generally recognized that in vivo gene transfection is one of the most important techniques used in the post-genome era. Above all, naked plasmid DNA transfection has attracted much attention because of its advantages including convenience of preparation and handling and lack of toxicity associated with the transfection agents. We have investigated tissue pressure-mediated transfection performed by light and controlled pressure of the target tissue after normal intravenous injection of plasmid DNA.

Pressure-mediated transfection of murine spleen and liver.

Extension of in vivo nucleic acid transfection techniques and increased information about those transfection properties and side effects are urgently needed to advance biological research and drug therapy. Tissue pressure-mediated transfection, involving lightly pressing the target tissue after intravenous injection of plasmid DNA or small-interfering RNA (siRNA), is a promising approach because of its high transfection efficiency and resulting low tissue damage. In this study, the gene expression/silencing properties and proinflammatory cytokine production associated with tissue pressure-mediated transfection were evaluated to extend its application.

Fluorescence response of a 4-trifluoroacetylaminophthalimide to iodide ions upon 254 nm irradiation in MeCN.

The title trifluoroacetylaminophthalimide derivative produced a violet fluorescence (lambdaFLmax 392 nm) in MeCN, and it displayed a green emission (lambdaFLmax 506 nm) after irradiation at 254 nm in the presence of iodide ions. The corresponding amidate ion of the trifluoroacetamide was identified as the green fluorescence emitter. The deprotonation reaction may be caused by proton-abstracting solvated electrons generated by a photochemical charge--transfer-to-solvent process from I(-) to MeCN.

Photoreaction of a 2,11-diaza[3.3]paracyclophane derivative: formation of octahedrane by photochemical dimerization of benzene.

Upon photoirradiation at 300 nm, the title diazaparacyclophane (R = COCF3) provided an octahedrane by the photodimerization of its benzene chromophores. This is the first photochemical formation of octahedrane, namely, via the dimerization of benzene. No octahedrane formation was observed for the photolysis of corresponding carbon-bridged paracyclophane.

Novel parallel reaction between a [1,5] sigmatropic alkylthio shift and a [1,5] sigmatropic hydrogen shift observed in a 2H-azepine ring.

Although heating 2-methoxy-2H-azepine results in a [1,5] sigmatropic hydrogen shift, heating 2-propylthio-2H-azepine results in not only a [1,5] sigmatropic hydrogen shift but also a [1,5] sigmatropic propylthio shift. Kinetic measurements reveal that migratory aptitudes increase in the order of MeO < H, PrS. These [1,5] sigmatropic shifts are discussed on the basis of ab initio DFT calculations.

Electrophilic behavior of the pi delocalized azepinium ion: Friedel-Crafts reactions with benzenes and five-membered aromatic heterocycles.

[reaction: see text] Although the reactivity of tropylium ion with aromatic substrates is low, the reaction of azepinium ion with aromatic substrates such as benzene, phenol, furan, and thiophene resulted in the formation of 2-aryl-2H-azepine as a major product. An exceptional result in the formation of ring-contracted product was observed in the reaction with pyrrole.

Reaction of 2-methoxy-3H-azepine with NBS: efficient synthesis of 2-substituted 2H-azepines.

[reaction: see text] The reaction of 2-methoxy-3H-azepines, in the presence or absence of a nucleophile, with N-bromosuccinimide (NBS) gave a regioselective 1,4-adduct from which the corresponding 2H-azepine derivatives were formed via base-promoted hydrogen bromide elimination, generally in moderate to quantitative yield. Competitive formation of 4-bromo-2-methoxy-3H-azepine by electrophilic substitutuion or 3H-azepin-2-yl 2H-azepin-2-yl ether by transetherification was minimized at lower reaction temperatures. Quantitative substitution of 2-(2',4',6'-trichlorophenoxy)-2H-azepine derivatives, formed in moderate yield from the respective 3H-azepine and NBS in the presence of 2,4,6-trichlorophenol (TCP), by various nucleophiles gave the corresponding 2-substituted 2H-azepine.

Triplet-sensitized photolysis of the photoisomer of a 2,11-diaza[3,3](9,10)anthracenoparacyclophane: an adiabatic cycloreversion and a [2pia + 2pia + 2sigmas] rearrangement in a triplet state of the biplanophane system.

The triplet-sensitized photoreactions of the title biplanophane system 6, the photoisomer of a 2,11-diaza[3,3](9,10)anthracenoparacyclophane derivative 5, were investigated by stationary and laser-flash photolyses using xanthone (XT) and benzophenone (BP) as triplet sensitizers. When photoisomer 6 underwent XT-sensitized irradiation, a triplet cyclophane 5 and a novel polycyclic product 7 were obtained via an adiabatic cycloreversion and a formal [2pia + 2pia + 2sigmas] rearrangement, respectively. The maximum quantum yield for the formation of cyclophane 5 (0.

Cycloaddition-Rearrangement Sequence of 2-Amido Substituted Furans as a Method of Synthesizing Hexahydroindolinones.

A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels-Alder cycloaddition (IMDAF) reaction of 2-amido substituted furans. The initially formed [4 + 2] cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge.

A Cycloaddition Approach toward the Synthesis of Substituted Indolines and Tetrahydroquinolines.

The intramolecular Diels-Alder reaction of 2-substituted aminofurans (IMDAF) results in the formation of various indolines and tetrahydroquinolines. The isolation of these ring systems from the IMDAF reaction can be rationalized in terms of an initial [4 + 2]-cycloaddition that first produces an oxa-bridged cycloadduct, which was not detected since it readily underwent nitrogen-assisted ring opening. Proton exchange followed by an eventual dehydration provides the aromatic product.