RESUMO
The aim of the study was to assess the efficacy/safety of once- (100 mg q.d.) or twice-daily (50 mg b.i.d.) sitagliptin 100 mg/day in Japanese patients with type 2 diabetes (T2DM). In this randomized, double-blind study, 80 patients with inadequate glycemic control (HbA1c=6.5-10%; FPG =15.0 mmol/l) were randomized equally to sitagliptin 100 mg q.d., 50 mg b.i.d. or placebo for 4 weeks. At baseline and Week 4, frequent blood sampling was performed to assess 24-h weighted mean glucose (24-h WMG). Patients in the efficacy analyses (n=76) had a mean baseline HbA1c of 7.7%. At Week 4, least-squares mean changes in 24-h WMG were reduced with sitagliptin 100 mg q.d. and 50 mg b.i.d. versus placebo (-1.9, -1.6, and -0.5 mmol/l, respectively; p<0.001). Sitagliptin significantly improved FPG and 2-h PPG compared to placebo. No significant differences in 24-h WMG, FPG, or 2-h PPG were observed between the sitagliptin groups. Sitagliptin was well tolerated with no hypoglycemic events. In Japanese patients with T2DM, sitagliptin 100 mg/day provided substantial and continuous 24-h glucose-lowering over 4 weeks. The same glucose-lowering efficacy and tolerability were observed with sitagliptin 100 mg/day whether administered as a once-daily or twice-daily regimen. These results support a once-daily dosing regimen in Japanese patients with T2DM.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Pirazinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Glicemia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Tolerância a Medicamentos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/toxicidade , Japão , Pessoa de Meia-Idade , Seleção de Pacientes , Placebos , Pirazinas/toxicidade , Fosfato de Sitagliptina , Triazóis/toxicidade , Adulto JovemRESUMO
The invariant mass spectra of phi-->K+K- are measured in 12 GeV p+A reactions in order to search for the in-medium modification of phi mesons. The observed K+K- spectra are well reproduced by the relativistic Breit-Wigner function with a combinatorial background shape in three betagamma regions between 1.0 and 3.5. The nuclear mass number dependence of the yields of the K+K- decay channel is compared to the simultaneously measured e+e- decay channel for carbon and copper targets. We parameterize the production yields as sigma(A)=sigma0Aalpha and obtain alphaphi-->K+K- -alphaphi-->e+e- to be 0.14+/-0.12. Limits are obtained for the partial decay widths of the phi mesons in nuclear matter.
RESUMO
Invariant mass spectra of e(+) e(-) pairs have been measured in 12 GeV p + A reactions to detect possible in-medium modification of vector mesons. Copper and carbon targets are used to study the nuclear-size dependence of e(+) e(-) invariant mass distributions. A significant excess on the low-mass side of the phi meson peak is observed in the low betagamma(= beta/square root(1-beta(2))) region of phi mesons (betagamma < 1.25) with copper targets. However, in the high betagamma region (betagamma > 1.25), spectral shapes of phi mesons are well described by the Breit-Wigner shape when experimental effects are considered. Thus, in addition to our earlier publications on rho/omega modification, this study has experimentally verified vector meson mass modification at normal nuclear density.
RESUMO
The invariant mass spectra of e+e- pairs produced in 12 GeV proton-induced nuclear reactions are measured at the KEK Proton Synchrotron. On the low-mass side of the meson peak, a significant enhancement over the known hadronic sources has been observed. The mass spectra, including the excess, are well reproduced by a model that takes into account the density dependence of the vector meson mass modification, as theoretically predicted.
RESUMO
In order to clarify the peroxisomal membrane proteins (PMPs), we characterized one of the major PMPs, PMP38. The deduced amino acid sequence for its cDNA in Arabidopsis thaliana contained polypeptides with 331 amino acids and had high similarity with those of Homo sapiens PMP34 and Candida boidinii PMP47 known as homologues of mitochondrial ATP/ADP carrier protein. We expected PMP38 to be localized on peroxisomal membranes, because it had the membrane peroxisomal targeting signal. Cell fractionation and immunocytochemical analysis using pumpkin cotyledons revealed that PMP38 is localized on peroxisomal membranes as an integral membrane protein. The amount of PMP38 in pumpkin cotyledons increased and reached the maximum protein level after 6 d in the dark but decreased thereafter. Illumination of the seedlings caused a significant decrease in the amount of the protein. These results clearly showed that the membrane protein PMP38 in glyoxysomes changes dramatically during the transformation of glyoxysomes to leaf peroxisomes, as do the other glyoxysomal enzymes, especially enzymes of the fatty acid beta-oxidation cycle, that are localized in the matrix of glyoxysomes.
Assuntos
Proteínas de Transporte/genética , Cotilédone/metabolismo , Cucurbitaceae/metabolismo , Glioxissomos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Peroxissomos/metabolismo , Proteínas de Plantas , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Senescência Celular , Cotilédone/crescimento & desenvolvimento , Cucurbitaceae/genética , Cucurbitaceae/crescimento & desenvolvimento , Glioxissomos/genética , Humanos , Immunoblotting , Membranas Intracelulares/metabolismo , Luz , Proteína Mitocondrial Trifuncional , Dados de Sequência Molecular , Complexos Multienzimáticos/metabolismo , Peroxissomos/genética , Transporte Proteico , Homologia de Sequência de AminoácidosRESUMO
Continuously excited free oscillations of the whole Earth have been found in the ground noise in a frequency band of long-period surface waves. Here we report evidence of an annual variation of this phenomenon, indicating that the excitation source is not within the solid Earth. There is evidence that these seismic free oscillations resonate with acoustic free oscillations of the atmosphere. The observed amplitudes suggest that the excitation source is at or just above Earth's surface.
RESUMO
Earth's free oscillations were considered to be transient phenomena occurring after large earthquakes. An analysis of records of the IDA (International Deployment of Accelerometers) gravimeter network shows that Earth is freely oscillating at an observable level even in seismically inactive periods. The observed oscillations are the fundamental spheroidal modes at frequencies between 2 and 7 millihertz. Numerical modeling indicates that these incessant excitations cannot be explained by stacked effects of a large number of small earthquakes. The observed "background" free oscillations represent some unknown dynamic process of Earth.
RESUMO
Three cardenolide glycosides, calotropin (1), frugoside (2), and 4'-O-beta-D-glucopyranosylfrugoside (3), were obtained as the cytotoxic principles of "akond mul" (roots of Calotropis gigantea L.). The cytotoxicity of these compounds against various cell lines of human and mouse origin was tested. They showed similar cell line selectivity to those of cardiac glycosides such as digoxin and ouabain: they are toxic to cell lines of human origin, but not to those from mouse at 2 micrograms/ml.
Assuntos
Antineoplásicos/isolamento & purificação , Proteínas de Ligação ao Cálcio/isolamento & purificação , Digitoxigenina/análogos & derivados , Glucosídeos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/farmacologia , Proteínas de Ciclo Celular , Digitoxigenina/química , Digitoxigenina/isolamento & purificação , Digitoxigenina/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Camundongos , Plantas Medicinais , Proteína A6 Ligante de Cálcio S100 , Proteínas S100 , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Recent seismic tomography of the Earth's mantle has revealed a large-scale pattern of mantle convection comprising upwelling columnar plumes in the Pacific and Africa and downwelling planar sheets along the Circum Pacific. Upwelling and downwelling occur most extensively under the south Pacific and west Pacific, respectively. High-resolution image of plate subduction has been obtained from the dense seismic networks around Japan. Japanese seismologists are in the best position to resolve the internal structure of downwelling current as an integral part of the whole convection system.