RESUMO
BACKGROUND: Airway eosinophils are considered to play an important role in the pathogenesis of asthma. Interleukin-5 is believed to be a key cytokine for the development, proliferation and activation of eosinophils. Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody that depletes blood and airway eosinophils. We conducted a phase 2a study in South Korea and Japan to evaluate the effect of benralizumab in an East Asian population. The primary objective was to evaluate the effect of benralizumab in adults with uncontrolled eosinophilic asthma with 2-6 incidences of exacerbations in the past year using a medium/high dose of inhaled corticosteroids and long-acting ß2-agonists. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. The subjects (n = 106) were randomized into four groups: placebo (n = 27) or benralizumab 2 mg (n = 27), 20 mg (n = 26) and 100 mg (n = 26). Benralizumab or placebo were administered subcutaneously on weeks 0 (day 1), 4, 8, 16, 24, 32 and 40. The primary endpoint was the asthma exacerbation rate at week 52. RESULTS: The asthma exacerbation rate was reduced by 33, 45 or 36% versus the placebo group when treated with 2, 20 or 100 mg of benralizumab, respectively. The percent mean change in forced expiratory volume at 1 s increased with each of the three doses in subjects treated with benralizumab. CONCLUSIONS: Benralizumab reduced asthma exacerbation and improved lung function and asthma control in adults with uncontrolled eosinophilic asthma.
Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Eosinófilos/patologia , Escarro , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Biomarcadores , Progressão da Doença , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Humanos , Japão , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-5/antagonistas & inibidores , República da Coreia , Testes de Função Respiratória , Escarro/citologia , Resultado do TratamentoRESUMO
Pulse-mode operation was realized in spin-polarized transmission electron microscopy (SP-TEM) using a laser-driven electron gun with a GaAs-GaAsP strained-layer-superlattice photocathode. TEM images were acquired with a pulsed electron beam with a 5-µs pulse duration. Phase locking of wobbling TEM images was demonstrated using a pulsed beam with a 1-kHz repetition frequency, which matched the image wobbling frequency. It was found that in composite images formed by superimposing 2 × 10(4) separate single-pulse exposures, the amount of image blurring due to wobbling was a linear function of the pulse duration. These results suggest the possibility of pump-probe measurements in SP-TEM using the pulsed electron beam as a probe, allowing nanometer-scale time-resolved spin mapping.
RESUMO
New glycosides of seven acetophenone derivatives (1-7) and two phenylpropanoids (8, 9), named juniperosides III-XI, have been isolated from the MeOH extract of the leaves and stems of Juniperus occidentalis Hook. (Cupressaceae), together with eleven other known compounds. The structures of these compounds have been successfully elucidated using a variety of spectroscopic techniques.
Assuntos
Acetofenonas/química , Glicosídeos/química , Juniperus/química , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/químicaRESUMO
Two new phenylpropanoid glycosides were isolated from the leaves and stems of Juniperus communis var. depressa (Cupressaceae) along with 14 known compounds. Their structures were determined by spectral analyses, in particular by 2D-NMR spectral evidence.
Assuntos
Glicosídeos/química , Juniperus/química , Extratos Vegetais/química , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/químicaRESUMO
A high-voltage dc photocathode electron gun was successfully conditioned up to a voltage of 550 kV and a long-time holding test for 8 h was demonstrated at an acceleration voltage of 500 kV. The dc photocathode electron gun is designed for future light sources based on energy-recovery linac and consists of a Cockcroft-Walton generator, a segmented cylindrical ceramic insulator, guard-ring electrodes, a support-rod electrode, a vacuum chamber, and a pressurized insulating gas tank. The segmented cylindrical ceramic insulator and the guard-ring electrodes were utilized to prevent any damage to the insulator from electrons emitted by the support-rod electrode.
RESUMO
The light extraction efficiency of top-emitting organic light-emitting diodes (OLEDs) was improved by insertion of a two-dimensional (2D) diffraction layer. The 2D diffraction layer was fabricated by our original nanofabrication technique, the embedded particle monolayer method, which could form a self-assembled particle monolayer. As a result, the electroluminescence intensity of the device with the 2D diffraction layer was improved by 1.67 times (in total luminous flux) and 2.07 times (in peak wavelength). High luminance top-emitting OLEDs were fabricated using the potentially low-cost self-assembling technique.
RESUMO
Three novel furoquinoline alkaloid oxogeranyl ethers (1-3) and one known furoquinoline alkaloid (4) were isolated from the leaves of Boninia glabra, an endemic plant of the Bonin Islands. Their structures were elucidated on the basis of spectroscopic analysis.
Assuntos
Alcaloides/isolamento & purificação , Quinolinas/isolamento & purificação , Rutaceae/química , Japão , Espectroscopia de Ressonância Magnética , Folhas de Planta/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
A chloroform extract of the leaves of Juniperas taxifolia exhibited a marked antiproliferative effect on human promyelocytic leukemia HL-60 cells at a concentration of 2.5 microg/ml. Deoxypodophyllotoxin (4) was identified in the extract as an outstanding antiproliferative compound, and five diterpenes (1-3, 5, and 6) were isolated as known compounds with weak or no cytotoxicity. These compounds were examined for their respective apoptosis- and differentiation-inducing activities toward HL-60 cells by DNA fragmentation and NBT-reducing assays, respectively. Among them, 7alpha-hydroxysandaracopimaric acid (6) was found to have a potent differentiation-inducing activity in a dose-dependent manner at 0.125-2 microg/ml (0.39-6.29 microM), together with apoptosis-inducing activity at concentrations of more than 2.5 microg/ml (7.86 microM). Deoxypodophyllotoxin (4) that exerted cytotoxic and apoptosis-inducing activities at 2 ng/ml (5 nM) did not induce differentiation at the same concentration, and the other diterpenes (1-3 and 5) showed no effect on cell differentiation, even at 5 microg/ml. It was thus demonstrated for the first time that 7alpha-hydroxysandaracopimaric acid was an effective differentiation-inducing compound toward HL-60 cells.
Assuntos
Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Juniperus/química , Leucemia Promielocítica Aguda/patologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Células HL-60 , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
This review describes chemical and biological studies on natural products achieved by the author for the latest 47 years and its main contents are composed of the following researches of the eight sections, entitled 1) Hopane-type triterpenes from a lichen, Parmelia leucotyliza, 2) Spirostanol and frostanol glycosides from Metanarthecium luteo-viride (Liliaceae), 3) Selective reduction of double bonds: preparation of 22,23-dihydroergosterol from ergosterol, 4) Compositions and structures of fragrant sesquiterpenes from several types of agarwoods, 5) Triterpenes and other components from Meliaceous plants, 6) Constituents of seeds of crude drugs and medicinal plants, 7) Hopane-type triterpene glycosides from a fern, Diplazium subsinuatum, 8) Search and structural elucidation of biologically active components from American plants obtained from United States of America (Oregon and California), Mexico, Guatemala, and Honduras. In this review, many classes of natural products, i.e., terpenoids (mono-, sesqui-, di-, and triterpenoids), steroids, glycosides, saponins, tannins, phenylpropanoids, lignans, flavonoids (flavones, flavonols, flavanones, biflavones, flavan-3-ols, etc.), etc. are dealt with and referred to.
Assuntos
Preparações de Plantas/química , Plantas Medicinais/química , Ergosterol/química , Ergosterol/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Conformação Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Espirostanos/química , Espirostanos/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
A new ursane-type triterpene, named as cheiranthic acid (1), was isolated from the MeOH extract of whole plants of Oenothera cheiranthifolia (Onagraceae) along with an isomeric pair of known oleanane- and ursane-type triterpenes (arjunolic acid and asiatic acid) and three flavonol glucuronide analogues (quercetin 3-O-glucuronide, its n-butyl ester, and myricetin 3-O-glucuronide). Their structures were elucidated based on spectroscopic evidence.
Assuntos
Flavonóis/isolamento & purificação , Glucuronídeos/isolamento & purificação , Oenothera/química , Plantas Medicinais/química , Triterpenos/isolamento & purificação , Ésteres/química , Ésteres/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonóis/química , Glucuronídeos/química , Isomerismo , Metanol/química , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Extratos Vegetais/química , Quercetina/análogos & derivados , Quercetina/química , Quercetina/isolamento & purificação , Análise Espectral , Triterpenos/químicaRESUMO
A new flavone xyloside, 1, and two new flavan-3-ol glucosides, 3 and 4, were isolated together with three known flavones, 2, 11, and 12, five known flavans, 5-9, and a known dihydrochalcone, 10, from the stems and leaves of Juniperus communis var. depressa (Cupressaceae) collected in Oregon, U.S.A., and their structures were determined on the basis of spectral evidence. A novel flavone nucleus such as that in 1 is seldom found in nature today, and new methylcatechin glucosides 3 and 4 are also rare in nature. In addition, we investigated the inhibitory activity of individual components, i.e., 8-11, and others, that were abundantly isolated from the same plant material for the Maillard reaction.
Assuntos
Flavonas/química , Glucosídeos/isolamento & purificação , Glicosídeos/isolamento & purificação , Juniperus/química , Glucosídeos/química , Glicosídeos/química , Reação de Maillard , Estrutura Molecular , Análise EspectralRESUMO
Two unusual triterpenoids, (24S)-24-methyl-25,32-cyclo-5alpha-lanosta-9(11)-en-3beta-ol and (24S)-24-methyl-25,32-cyclo-cycloartane-3beta-ol, were isolated from leaves of Pandanus boninensis along with known triterpenoids and lignans. Their structures were established on the basis of spectroscopic methods and X-ray analysis.
Assuntos
Pandanaceae/química , Triterpenos/química , Cristalografia por Raios X , Lignanas/química , Lignanas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Triterpenos/isolamento & purificaçãoRESUMO
A new monoterpene glucoside (1) and three new natural megastigmane glycosides (2-4) were isolated along with a known megastigmane glucoside (5) from twigs with leaves of Juniperus communis var. depressa (Cupressaceae) collected in Oregon, U.S.A., and their structures were determined on the basis of spectral and chemical evidence. In addition, the antibacterial activities of the isolated components against Helicobacter pylori were also investigated.
Assuntos
Cicloexanonas/isolamento & purificação , Glucosídeos/isolamento & purificação , Glicosídeos/isolamento & purificação , Juniperus/química , Monoterpenos/isolamento & purificação , Norisoprenoides/isolamento & purificação , Configuração de Carboidratos , Cicloexanonas/farmacologia , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Monoterpenos/farmacologia , Norisoprenoides/farmacologiaRESUMO
Fourteen flavonol glycosides including two new compounds were isolated from the leaves of two Diospyros plants (D. cathayensis and D. rhombifolia). The structures of isolated compounds were determined by spectroscopic analysis. The scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical of the isolated compounds was also investigated.
Assuntos
Diospyros , Flavonóis/isolamento & purificação , Glicosídeos/isolamento & purificação , Flavonóis/química , Glicosídeos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de PlantaRESUMO
A new 4alpha-aryltetralin-type lignan called burseranin (1) and a known analogous lignan picropolygamain (2) were isolated along with known triterpenes, lupeol and epi-lupeol from the methanol extract of stems of Bursera graveolens, which showed a remarkable inhibitory activity against human HT1080 fibrosarcoma cells. The whole structure of 1 was established based on combined spectral studies and the absolute structure for 2 was first confirmed by CD spectral evidence. In addition, cytotoxic activities of the stem (methanol) extract and its components are evaluated in this paper.
Assuntos
Antineoplásicos Fitogênicos/química , Bursera/química , Lignanas/química , Tetra-Hidronaftalenos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Dicroísmo Circular , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , México , Extratos Vegetais/química , Caules de Planta/química , Tetra-Hidronaftalenos/isolamento & purificação , Tetra-Hidronaftalenos/farmacologiaRESUMO
Two neolignan glycosides (junipercomnosides A and B) were isolated from aerial parts of Juniperus communis var. depressa along with two known neolignan glycosides and seven flavonoid glycosides. The structures of the isolated compounds were determined by spectral analysis, in particular by 2D-NMR analysis. The significance of distribution of flavonoids in the chemotaxonomy of genus Juniperus was also discussed.
Assuntos
Flavonoides/química , Glicosídeos/química , Juniperus/química , Lignanas/química , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Lignanas/isolamento & purificação , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Componentes Aéreos da Planta/químicaRESUMO
Possible molecular conformations in peptide nanorings and nanotubes were theoretically investigated by a mathematical conformation analysis as well as ab initio Hartree-Fock calculations. The mathematical analysis predicts not only the conventional nanorings having an extended-type (E-type) backbone (trans zigzag) but also the novel ones having bound-type (B-type) backbones with a smaller internal diameter. Ab initio calculations for the amino acid substitution reveal that all 20 encoded residues can form both types of the above nanorings as a local minimum. However, the energetically stable type is determined in accordance with the kind of the replaced side chains. Moreover, the present work theoretically reveals that both types of nanorings stack to form nanotubes through inter-ring hydrogen bonds, i.e., larger E-type nanotubes and smaller B-type nanotubes. Electronically, the HOMO and LUMO states of the nanoring and nanotube backbones are formed by the in-plane pi state. The replacement by the appropriate residues is furthermore predicted to intrude additional levels in the energy gap and to form the frontier states localized at the side chains.
Assuntos
Modelos Químicos , Nanotecnologia/métodos , Peptídeos Cíclicos/química , Ligação de Hidrogênio , Modelos Moleculares , Conformação ProteicaRESUMO
Two new phenol glucosides termed juniperosides I (1) and II (2) were isolated, together with known two biflavones, cupressuflavone and amentoflavone and a diterpene, 3beta-hydroxy sandaracopimaric acid, from leaves of Juniperus occidentalis HOOK. (Cupressaceae) collected in Oregon, U.S.A., and their structures were established as (1S)- and (1R)-1-(2'-hydroxy-6'-methylphenyl)ethanol 2'-O-beta-D-glucopyranosides (1, 2), respectively, on the basis of spectral, chemical, and synthetic evidence. The glycosides 1 and 2, as well as the corresponding aglycones 1a and 2a, are apparently novel types of naturally occurring compounds; to our knowledge, isolation of these types of natural phenol derivatives has only rarely been reported from the vegetable kingdom.
Assuntos
Diterpenos/química , Flavonoides/química , Glucosídeos/química , Juniperus/química , Fenol/química , Diterpenos/isolamento & purificação , Flavonoides/isolamento & purificação , Glucosídeos/isolamento & purificação , América do Norte , Fenol/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Estados UnidosRESUMO
A methanol extract of Coptidis Rhizoma effectively enhanced the outgrowth of neurite in PC12 cells induced by nerve growth factor (NGF). Following solvent partition and preparative HPLC, berberine was isolated as the major active compound. Berberine enhanced the proportion of neurite-bearing cells in a dose-dependent manner without cytotoxicity. Its structural relatives, palmatine and coptisine, showed a slightly weaker NGF-enhancing effect than berberine. These three alkaloids inhibited acetylcholinesterase activity at a level comparable to that of physostigmine, but this inhibition was not responsible for the potentiation of NGF-induced neurite outgrowth. It is demonstrated for the first time that protoberberine alkaloids potentiated the NGF-induced differentiation of neural cells.