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2.
Circ J ; 84(11): 1912-1921, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32981924

RESUMO

BACKGROUND: There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban.Methods and Results:In this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events. CONCLUSIONS: In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.

5.
Ann Vasc Dis ; 12(2): 182-186, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31275471

RESUMO

Objective: This multicenter observational study was conducted in order to investigate the incidence of cancer in patients with critical limb ischemia. Materials and Methods: We prospectively investigated the incidence of cancer in 68 patients with critical limb ischemia over a two-year period. Patients underwent an intensive examination at enrollment, which included tumor marker levels and chest and abdominal computed tomography, as well as one- and two-year follow-up examinations. We compared the observed incidence of cancer with the expected incidence calculated from national cancer rates by the standardized incidence ratio (SIR). Results: The majority (83.6%) of the patients were men, and 92.5% of the patients had a peripheral arterial disease that was classified as Fontaine stage III or IV. During enrollment, newly diagnosed cancers were detected in seven patients. Four additional cancers were detected during the follow-up period. All of the detected cancers were asymptomatic. We observed an increased risk of cancer (SIR, 4.04; 95% confidence interval, 1.31-9.42) in patients with critical limb ischemia. Conclusion: This study suggests that critical limb ischemia is associated with an increased risk of cancer. Our findings should be taken into serious consideration by future investigators considering the use of therapeutic angiogenesis.

6.
J Magn Reson ; 306: 80-85, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31337560

RESUMO

Superconducting magnet technology changed dramatically with the discovery of high temperature superconductors (HTS) in 1986, an event which drove the development of much higher field magnets. However, this technology paradigm shift has been delayed by as much as a decade in the case of NMR magnets. In this paper, we will provide a historical perspective to the reasons for this delay and assess the future prospects for high- and ultrahigh-field NMR magnets resulting from current trends in the development of HTS magnet technology.

7.
Biomacromolecules ; 20(3): 1394-1400, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30753057

RESUMO

The terminal groups of natural rubber (NR) are widely believed to play a crucial role in defining the excellent mechanical and other physical properties of processed NR products. Despite their presumed importance, the chemical structures of the terminal groups are elusive in widely used NR species with a high degree of polymerization, such as Hevea natural rubber (H-NR). In previous studies, structural analysis by solution NMR has been carried out on the terminal units of NR after chemical treatment involving chemical alterations, such as deproteinization with enzymes and other chemicals. However, there is concern that such chemical treatments may alter the properties of the terminal units. In this study, we established an NMR-based approach to analyze the structures of the terminal units in commercial H-NR without any chemical treatments, or with only a mild treatment of some samples, such as acetone extraction for removing the impurities. To suppress the signals of low-molecular-weight impurities, we have developed methods combining DOSY-based diffusion filters with multiple-WET (MWET) 2D-NMR, which we introduced previously to suppress strong signals from main-chain of polymer and solvents (Tanaka et al. Macromolecules, 2016, 49, 5750-5754). Using the new method and MWET 2D-NMR methods with high-field NMR at a 1H frequency of 900 MHz, we observed NMR signals of the terminal units of chemically untreated commercial H-NR for the first time. The NMR results for eight commercial H-NR samples consistently demonstrated the presence of at least five kinds of terminating-end (α-terminus) units of the H-NR polymer chain in addition to NMR signals for the initiating-end (ω-terminus) units. Our NMR analyses revealed for the first time that none of the α-terminal groups form a phosphate ester.


Assuntos
Hevea/química , Espectroscopia de Ressonância Magnética/métodos , Borracha/química , Estrutura Molecular
8.
BMJ Open ; 8(6): e020286, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29934383

RESUMO

INTRODUCTION: Rivaroxaban, a factor Xa inhibitor used as a direct oral anticoagulant, is beneficial over warfarin in terms of food-drug interactions and the need for therapeutic monitoring in patients with acute venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Because there is little data regarding VTE treatment in Japan, a real-world survey of Japanese patients being treated with rivaroxaban for VTE is needed. METHODS AND ANALYSIS: The Japanese Registry of Rivaroxaban Effectiveness & Safety for the Prevention of Recurrence in Patients with Deep Vein Thrombosis and Pulmonary Embolism has been established to investigate the clinical outcomes of rivaroxaban for the initial treatment and prevention of symptomatic recurrent VTE in Japanese patients with acute symptomatic/asymptomatic VTE. 150 institutions in Japan will enrol patients in the study; the target enrolment is 1000. All patients will be followed up two times a year for at least 18 months and up to 3 years after their enrolment. The primary outcome is symptomatic recurrent VTE occurring during the study period. The principal safety outcome is clinically relevant bleeding (ie, major bleeding or clinically relevant non-major bleeding) occurring during treatment. A clinical events committee will adjudicate all outcomes. ETHICS AND DISSEMINATION: The study protocol has been approved by the Nihon University Itabashi Hospital, Clinical Research Ethics Committee and all local institutional ethics committees of the participating hospitals. Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03091621,UMIN000025072; Pre-results.


Assuntos
Inibidores do Fator Xa/administração & dosagem , Embolia Pulmonar/tratamento farmacológico , Rivaroxabana/administração & dosagem , Trombose Venosa/tratamento farmacológico , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Estudos Prospectivos , Embolia Pulmonar/epidemiologia , Recidiva , Sistema de Registros , Projetos de Pesquisa , Fatores de Risco , Rivaroxabana/efeitos adversos , Trombose Venosa/epidemiologia , Varfarina/efeitos adversos , Varfarina/uso terapêutico
9.
J Nat Prod ; 80(11): 3010-3013, 2017 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-29099182

RESUMO

Houttuynoid M (1), a new houttuynoid, and the related known compound houttuynoid A (2) were isolated from Houttuynia cordata. Their structures were defined using NMR data analysis, HR-MSn experiment, and chemical derivatization. Houttuynoid M is the first example of a houttuynoid with a bis-houttuynin chain tethered to a flavonoid core. A putative biosynthetic pathway of houttuynoid M (1) is proposed. The anti-herpes simplex virus (anti-HSV) activities of 1 and 2 (IC50 values of 17.72 and 12.42 µM, respectively) were evaluated using a plaque formation assay with acyclovir as the positive control.


Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Houttuynia/química , Aciclovir/farmacologia , Aldeídos/química , Antivirais/química , Medicamentos de Ervas Chinesas/química , Flavonoides/química , Flavonoides/farmacologia , Glicosídeos/química , Estrutura Molecular
10.
Anal Sci ; 32(12): 1339-1345, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27941265

RESUMO

Solid-state NMR observations of low-gamma half-integer quadrupolar nuclei, 35Cl and 37Cl, were demonstrated using a 24 T hybrid magnet (1H resonance frequency of 1.02 GHz) comprised of the high-temperature (HTS) and low-temperature (LTS) superconductors, and compared with results using a 14.1 T standard NMR magnet. While at 24 T the linewidth is 1.7 times narrower than that at 14.1 T, the gain in the sensitivity is 7.0 times because of enhanced polarization, reduced linewidth, and the use of larger rotor. A simple theoretical model was used to rationalize the sensitivity enhancements. The ratio of 35Cl and 37Cl quadrupolar couplings agrees well with the ratio of quadrupolar moments, and no isotope-dependent chemical shift has been observed. In addition, the 3QMAS spectrum of 35Cl is shown to demonstrate the high sensitivity rendered by the 24 T spectrometer.

12.
Ann Thorac Cardiovasc Surg ; 22(5): 315-317, 2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26581497

RESUMO

PURPOSE: Cystic adventitial artery disease is an uncommon non-atherosclerotic peripheral vessel disease. Furthermore cystic adventitial disease of the common femoral artery is an extremely rare entity. We report the case of a 54 year-old man complaining of intermittent claudication who was referred to our vascular service. METHODS AND RESULTS: Doppler ultrasound and multidetector-row computed tomography (CT) with 3-dimensional volume rendering revealed severe stenosis with cystic an adventitial cyst in the common femoral artery. Intra-operative Doppler ultrasound showed the cyst to be multilocular type. Reversed great saphenous vein interposition was successfully placed. CONCLUSION: Removal of cyst together with artery and interposition using reversed great saphenous vein is the optimal treatment procedure to prevent recurrence.


Assuntos
Túnica Adventícia , Arteriopatias Oclusivas , Cistos , Artéria Femoral , Claudicação Intermitente , Túnica Adventícia/diagnóstico por imagem , Túnica Adventícia/cirurgia , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Arteriopatias Oclusivas/cirurgia , Biópsia , Angiografia por Tomografia Computadorizada , Cistos/diagnóstico por imagem , Cistos/fisiopatologia , Cistos/cirurgia , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Artéria Femoral/cirurgia , Humanos , Claudicação Intermitente/diagnóstico por imagem , Claudicação Intermitente/fisiopatologia , Claudicação Intermitente/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Veia Safena/transplante , Resultado do Tratamento , Ultrassonografia Doppler em Cores
13.
Anal Sci ; 31(12): 1267-72, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26656816

RESUMO

We developed a capillary chromatography system using a phase-separated solvent mixture as a carrier solution--i.e., a water-hydrophilic/hydrophobic organic solvent mixture--which we call "tube radial distribution chromatography" (TRDC). Here, we attempted to apply the TRDC system to a microchip incorporating microchannels with a double T-junction for injection of analyte solution and a three-to-one, narrow-to-wide channel confluence point for tube radial distribution phenomenon (TRDP) at room temperature. A ternary mixed solvent of water, acetonitrile and ethyl acetate was used as a carrier solution. TRDP in the wide microchannel was examined using various flow rates, temperatures, and component solvent ratios. Successful observation was carried out using a fluorescence microscope-CCD camera. Model analytes perylene (hydrophobic) and Eosin Y (hydrophilic) were separated by flowing through the microchannel, without any treatment such as packed columns or coating, at room temperature (25°C).

14.
J Magn Reson ; 261: 1-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26524647

RESUMO

This study reports a first successful demonstration of a single channel proton 3D and 2D high-throughput ultrafast magic angle spinning (MAS) solid-state NMR techniques in an ultra-high magnetic field (1020MHz) NMR spectrometer comprised of HTS/LTS magnet. High spectral resolution is well demonstrated.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Prótons , Campos Eletromagnéticos , Histidina/química , Ressonância Magnética Nuclear Biomolecular/métodos , Tirosina/química
15.
J Magn Reson ; 256: 30-33, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25978708

RESUMO

We have successfully developed a 1020MHz (24.0T) NMR magnet, establishing the world's highest magnetic field in high resolution NMR superconducting magnets. The magnet is a series connection of LTS (low-Tc superconductors NbTi and Nb3Sn) outer coils and an HTS (high-Tc superconductor, Bi-2223) innermost coil, being operated at superfluid liquid helium temperature such as around 1.8K and in a driven-mode by an external DC power supply. The drift of the magnetic field was initially ±0.8ppm/10h without the (2)H lock operation; it was then stabilized to be less than 1ppb/10h by using an NMR internal lock operation. The full-width at half maximum of a (1)H spectrum taken for 1% CHCl3 in acetone-d6 was as low as 0.7Hz (0.7ppb), which was sufficient for solution NMR. On the contrary, the temporal field stability under the external lock operation for solid-state NMR was 170ppb/10h, sufficient for NMR measurements for quadrupolar nuclei such as (17)O; a (17)O NMR measurement for labeled tri-peptide clearly demonstrated the effect of high magnetic field on solid-state NMR spectra.

16.
Thromb J ; 13: 2, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25717286

RESUMO

BACKGROUND: The global EINSTEIN DVT and PE studies compared rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily) with enoxaparin/vitamin K antagonist therapy and demonstrated non-inferiority for efficacy and superiority for major bleeding. Owing to differences in targeted anticoagulant intensities in Japan, Japanese patients were not enrolled into the global studies. Instead, a separate study of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in Japanese patients was conducted, which compared the Japanese standard of care with a reduced dose of rivaroxaban. METHODS: We conducted an open-label, randomized trial that compared 3, 6, or 12 months of oral rivaroxaban alone (10 mg twice daily or 15 mg twice daily for 3 weeks followed by 15 mg once daily) with activated partial thromboplastin time-adjusted intravenous unfractionated heparin (UFH) followed by warfarin (target international normalized ratio 2.0; range 1.5-2.5) in patients with acute, objectively confirmed symptomatic DVT and/or PE. Patients were assessed for the occurrence of symptomatic recurrent venous thromboembolic events or asymptomatic deterioration and bleeding. RESULTS: Eighty-one patients were assigned to rivaroxaban and 19 patients to UFH/warfarin. Three patients were excluded because of serious non-compliance issues. The composite of symptomatic venous thromboembolic events or asymptomatic deterioration occurred in 1 (1.4%) rivaroxaban patient and in 1 (5.3%) UFH/warfarin patient (absolute risk difference, 3.9% [95% confidence interval, -3.4-23.8]). No major bleeding occurred during study treatment. Clinically relevant non-major bleeding occurred in 6 (7.8%) patients in the rivaroxaban group and 1 (5.3%) patient in the UFH/warfarin group. CONCLUSIONS: The findings of this study in Japanese patients with acute DVT and/or PE suggest a similar efficacy and safety profile with rivaroxaban and control treatment, consistent with that of the worldwide EINSTEIN DVT and PE program. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01516840 and NCT01516814.

17.
SAGE Open Med Case Rep ; 3: 2050313X15591314, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27489691

RESUMO

A 40-year-old man underwent ascending aorta replacement for an acute type A aortic dissection. After the operations, methicillin-resistant Staphylococcus aureus was identified in sputum and blood cultures. Although anti-methicillin-resistant Staphylococcus aureus drugs were administered, most of the intermittent blood cultures remained positive. The focus of methicillin-resistant Staphylococcus aureus infection was not evident in the early stages, and no specific symptoms such as abscess or endocarditis were observed. However, abscesses in the brain, mediastinum and spleen were found 3 years after the operation. The minimum inhibitory concentration of vancomycin gradually increased from 1 to 4 µg/mL during the course of treatment. This case provides evidence for a potential role of combination therapy.

18.
J Struct Funct Genomics ; 15(4): 191-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25398586

RESUMO

We developed a method for efficient chromosome tagging in Pichia pastoris, using a useful tandem affinity purification (TAP) tag. The TAP tag, designated and used here as the THF tag, contains a thrombin protease cleavage site for removal of the TAP tag and a hexahistidine sequence (6× His) followed by three copies of the FLAG sequence (3× FLAG) for affinity purification. Using this method, THF-tagged RNA polymerases I, II, and III were successfully purified from P. pastoris. The method also enabled us to purify the tagged RNA polymerase II on a large scale, for its crystallization and preliminary X-ray crystallographic analysis. The method described here will be widely useful for the rapid and large-scale preparation of crystallization grade eukaryotic multi-subunit protein complexes.


Assuntos
Cromatografia de Afinidade/métodos , Proteínas Fúngicas/isolamento & purificação , Histidina/isolamento & purificação , Complexos Multiproteicos/isolamento & purificação , Pichia/química , Proteínas Fúngicas/biossíntese , Proteínas Fúngicas/genética , Histidina/biossíntese , Histidina/genética , Complexos Multiproteicos/biossíntese , Complexos Multiproteicos/genética , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação
19.
Sci Rep ; 4: 7199, 2014 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-25425181

RESUMO

Wet chemical reduction of metal ions, a common strategy for synthesizing metal nanoparticles, strongly depends on the electric potential of the metal, and its applications to late transition metal clusters have been limited to special cases. Here, we describe copper nanoclusters grown by synchrotron radiolysis in concert with wet chemistry. The local structure of copper aggregates grown by reducing Cu(II) pentanedionate using synchrotron x-ray beam was studied in situ by x-ray absorption spectroscopy. A detailed analysis of the XANES and EXAFS spectra, compared with DFT calculations and full-potential non-muffin-tin multiple scattering calculations, identified the nanocluster as Cu13 with icosahedral symmetry. The novel "charged" nanoclusters tightly bound to electron-donating amido molecules, which formed as a result of photo-induced deprotonation of ligand amines, were stabilized by irradiation. Monodispersive deposition of nanoclusters was enabled by controlling the type and density of "monomers", in remarkable contrast to the conventional growth of metallic nanoparticles.

20.
Circ J ; 78(3): 708-17, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24401573

RESUMO

BACKGROUND: Epidemiology and clinical management of acute venous thromboembolism (VTE) are not readily available in Japan. METHODS AND RESULTS: The Japan VTE Treatment Registry (JAVA) is a multicenter cohort study of consecutive patients with an objectively confirmed, symptomatic acute pulmonary embolism (PE), symptomatic acute deep vein thrombosis (DVT), or asymptomatic acute proximal DVT. Of the 1,076 patients enrolled with acute VTE, 68.7% presented with an isolated DVT; 17.0% had PE alone; and 14.4% had both. VTE management was characterized by a high rate of inferior vena cava filter insertion (40.6%), frequent thrombolysis (21.1%), and sub-therapeutic unfractionated heparin-based anticoagulation, followed by warfarin prescription, mostly targeting an international normalized ratio of 2.0 (range, 1.5-2.5). During a mean observation period of 252.5 days, 29 recurrent cases of VTE were documented, yielding an incidence rate of 3.9 per 100 patient-years. A total of 123 patients died during the study period, corresponding to a rate of 16.6 deaths per 100 patient-years. The incidence of major bleeding was 3.2% per patient-year, including 2 fatal hemorrhages and 7 intracranial hemorrhages. CONCLUSIONS: VTE management in Japan is characterized by a highly aggressive strategy in the acute phase, in contrast to protocols that use low-level anticoagulation. The VTE recurrence rates in Japan and Western countries are similar, but mortality is higher in Japan, with significant variability depending on patient and management characteristics.


Assuntos
Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/terapia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Feminino , Humanos , Coeficiente Internacional Normatizado , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/mortalidade , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia Trombolítica/métodos , Filtros de Veia Cava , Varfarina/administração & dosagem , Varfarina/efeitos adversos
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