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1.
Viruses ; 13(6)2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198717

RESUMO

In this study, we investigated severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) infection in cats in Nagasaki, Japan. In total, 44 of 133 (33.1%) cats with suspected SFTS were confirmed to be infected with SFTSV. Phylogenetic analyses of SFTSV isolates from cats indicated that the main genotype in Nagasaki was J1 and that unique reassortant strains with J2 (S segment) and unclassified genotypes (M and L segments) were also present. There were no significant differences in virus growth in cell cultures or fatality in SFTSV-infected mice between the SFTSV strains that were isolated from recovered and fatal cat cases. Remarkably, SFTSV RNAs were detected in the swabs from cats, indicating that the body fluids contain SFTSV. To evaluate the risk of SFTSV infection when providing animal care, we further examined the seroprevalence of SFTSV infection in veterinarian staff members; 3 of 71 (4.2%) were seropositive for SFTSV-specific antibodies. Our results provide useful information on the possibility of using cats as sentinel animals and raised concerns of the zoonotic risk of catching SFTSV from animals.


Assuntos
Doenças do Gato/epidemiologia , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Médicos Veterinários , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Doenças do Gato/virologia , Gatos , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Japão/epidemiologia , Phlebovirus/classificação , Phlebovirus/genética , Filogenia , RNA Viral , Febre Grave com Síndrome de Trombocitopenia/veterinária , Febre Grave com Síndrome de Trombocitopenia/virologia
2.
Yakugaku Zasshi ; 140(6): 763-766, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32475924

RESUMO

The Japanese Pharmacopoeia (JP) is an official document that defines the specifications, criteria, and standard test methods necessary to properly ensure the quality of medicines in Japan. To ensure the efficacy and safety of pharmaceutical products, it is essential to establish standards that ensure their quality. For this purpose, the JP aims to include all drugs that are important from the viewpoint of healthcare and medical treatment, and description of each monograph of medicine is maintained and improved so that those standards can be generally practiced. In addition, to play a key role as the official document in the field of pharmaceutical product quality, JP contents are enhanced by proactively introducing the latest scientific knowledge and technologies. As the international manufacturing of pharmaceutical products and their raw materials that are distributed in Japan is increasing, the JP has recently begun to promote the international harmonisation of pharmaceutical excipients and general tests through the Pharmacopoeial Discussion Group (PDG) and to swiftly implement the harmonised items in the JP. In addition, the JP will implement internationally harmonised concepts and specifications for pharmaceutical products, e.g., the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), to define the latest concepts of quality control for pharmaceutical products in the official document. We introduce the implementation of the latest scientific knowledge, technologies, and activities for international harmonisation of the JP.


Assuntos
Biofarmácia/normas , Cooperação Internacional , Conhecimento , Farmacopeias como Assunto , Humanos , Japão , Controle de Qualidade
3.
Am J Trop Med Hyg ; 102(6): 1217-1225, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32189614

RESUMO

Dengue virus (DENV) infection is a major cause of morbidity and mortality in Vietnam, and the incidence is higher and more consistent in the southern part of the country. This study investigated the circulation of DENV serotypes, viremia levels, immunological status, and cytokine levels, with disease severities among children infected in 2017 in Ho Chi Minh City, Southern Vietnam. Acute and convalescent serum samples were collected from clinically diagnosed dengue children. They were confirmed to have DENV infection by NS1 antigen, IgM and IgG ELISAs, virus isolation, and conventional and real-time RT-PCR. Measurement of 10 cytokine levels was performed in the serum samples. All the children were dengue IgM positive; 28% and 72% of them had primary and secondary DENV infections, respectively, whereas 54% of those with secondary infection were children with dengue with warning signs and with severe dengue. Any or mixed infection of the four serotypes of DENV RNA was detected in 58 children. Twenty DENV strains (DENV-1 = 16 and DENV-4 = 4) were isolated. Levels of IFN-γ, TNF-α, MCP-1, IL-10, and IL-6 were significantly higher in severe dengue cases. We report the predominance of DENV-1 over other serotypes in the 2017 dengue outbreak in Southern Vietnam. Our data showed that cytokine expressions were correlated with dengue pathogenesis and may help in identifying an effective therapeutic strategy.


Assuntos
Citocinas/sangue , Dengue/sangue , Dengue/epidemiologia , Adolescente , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Dengue/metabolismo , Dengue/patologia , Surtos de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Masculino , Estudos Retrospectivos , Vietnã/epidemiologia
4.
J Clin Virol ; 125: 104304, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32145478

RESUMO

BACKGROUND: Sri Lanka experienced its largest dengue outbreak in 2017 with more than 185,000 dengue cases including at least 250 fatalities. OBJECTIVES: Our study aimed to characterize the clinical, immunological and virological features of confirmed dengue patients in Sri Lanka during the outbreak in 2017 when unusual manifestations of severe dengue were observed. STUDY DESIGN: Sera from 295 patients who were admitted to Teaching Hospital Kandy, Kandy, Sri Lanka between March 2017- January 2018 were subjected to NS1 antigen, IgM and IgG ELISAs, virus isolation, conventional and real time RT-PCR and next generation sequencing. RESULTS: Primary and secondary infections were detected in 48.5 % and 51.5 % of the study population, respectively. Two hundred twenty five DENV strains were isolated (219 DENV-2, one DENV-3, two DENV-4, two mixed infections of DENV-2 and -3 and one mixed infection of DENV-2 and -4). Unusual and severe manifestations such as encephalitis, encephalopathy, liver failure, kidney failure, myocarditis, Guillain-Barré syndrome and multi-organ failure were noted in 44 dengue patients with 11 deaths. The viraemia levels in patients with primary infection and unusual manifestations were significantly higher compared to those in patients with secondary infection. A new clade of DENV-2 Cosmopolitan genotype strains was observed with the strains closely related to those from China, Malaysia, Indonesia, Singapore and Taiwan. CONCLUSIONS: The new clade of DENV-2 cosmopolitan genotype observed in Sri Lanka in 2017 caused an unprecedented, severe dengue outbreak. The emergence of DENV-3 and DENV-4 in the 2017 outbreak might cause future outbreaks in Sri Lanka.


Assuntos
Vírus da Dengue/genética , Dengue/complicações , Dengue/epidemiologia , Doenças do Sistema Nervoso/virologia , Dengue Grave/epidemiologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Coinfecção/complicações , Coinfecção/epidemiologia , Coinfecção/virologia , Dengue/mortalidade , Vírus da Dengue/classificação , Vírus da Dengue/patogenicidade , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Feminino , Genótipo , Humanos , Imunoglobulina M/sangue , Lactente , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Filogenia , RNA Viral/genética , Dengue Grave/mortalidade , Sri Lanka/epidemiologia , Adulto Jovem
5.
J Mater Chem B ; 8(7): 1489-1495, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31998931

RESUMO

Stimuli-responsive materials have been actively researched over the past few decades. Among such materials, spiropyran is one of the most attractive compounds because the structure and polarity of the material are dramatically changed after photo irradiation, unlike other materials. In this work, we designed and synthesized a spiropyran derivative (SpMA) with a methacryloyl group on the nitrobenzene ring of a spiropyran skeleton. The UV spectra of the newly synthesized SpMA showed the photo-isomerization of spiropyran. The maximum absorption wavelength (λmax) of SpMA was 616 nm in n-hexane, a nonpolar solvent, although λmax of SpMA was 532 nm in methanol, a polar protic solvent, which resulted in an 84 nm blue-shift. SpMA was successfully polymerized by ruthenium (Ru)-catalyzed living radical polymerization. Poly(SpMA) (PSpMA) was then spin-coated on a PET substrate in order to control the surface properties of water repellency and cell adhesion. The water repellency was decreased approximately 10° under UV irradiation, because of the polarity change of PSpMA caused by photo-isomerization from the spiropyran (SP) type to the merocyanine (MC) type. In addition, NIH3T3 cells were spread only on 6% of the surface of the PSpMA thin film after UV irradiation compared with no UV irradiation. The polarity change of PSpMA by photo-isomerization is also believed to be the reason for this behavior. As a result, we successfully synthesized a photo-controllable cell culture scaffold.


Assuntos
Benzopiranos/farmacologia , Indóis/farmacologia , Metacrilatos/farmacologia , Nitrocompostos/farmacologia , Polímeros/farmacologia , Animais , Benzopiranos/síntese química , Benzopiranos/química , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Indóis/síntese química , Indóis/química , Metacrilatos/química , Camundongos , Estrutura Molecular , Células NIH 3T3 , Nitrocompostos/síntese química , Nitrocompostos/química , Tamanho da Partícula , Polímeros/síntese química , Polímeros/química , Tomografia por Emissão de Pósitrons , Propriedades de Superfície
6.
Chem Pharm Bull (Tokyo) ; 67(12): 1301-1313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787657

RESUMO

A pharmacopoeia's core mission is to protect public health by creating and making available public standards to help ensure the quality of drugs. In recent years, pharmacopoeias around the world have harmonized their standards in the present context of globalized drug supply chains and markets. For example, the Pharmacopoeial Discussion Group has worked to harmonize excipient monographs and general chapters. In addition, the International Meeting of World Pharmacopoeias has been held by the WHO to discuss information exchange and international collaboration, among other topics. To contribute further to the protection of public health in the globalized drug market, we conducted a comparative study of the pharmacopoeias in Japan, Europe, and the United States. We aimed to examine current differences among the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia-National Formulary and to identify areas that require further collaboration among the three pharmacopoeias. In this study, we analyzed monographs and general chapters listed in the three pharmacopoeias. We identified the features of the monographs and general chapters listed in each pharmacopoeia, as well as differences across the pharmacopoeias. Moreover, on the basis of our findings, we suggest standards that require further collaboration among the pharmacopoeias in certain preferred areas. The comparison data produced by this study are expected to be used to develop strategies for future revisions of pharmacopoeias around the world.


Assuntos
Química Farmacêutica/normas , Europa (Continente) , Humanos , Japão , Estados Unidos
7.
Emerg Infect Dis ; 25(11): 2127-2128, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31625854

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) can be transmitted between humans. We describe a case of severe fever with thrombocytopenia syndrome in which SFTSV RNA was detected in semen after its disappearance from serum. Our findings indicate possible sexual transmission of this emerging virus.


Assuntos
Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/virologia , Phlebovirus/genética , RNA Viral , Sêmen/virologia , Infecções por Bunyaviridae/transmissão , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública
8.
J Biomater Sci Polym Ed ; 30(13): 1161-1171, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31200621

RESUMO

We have developed biocompatible scaffolds that enable cell fate control with visible light. The scaffolds are based on synthetic collagen-like polypeptide, poly(prolyl-hydroxyprolyl-glycyl) {poly(Pro-Hyp-Gly)} which has been used for cosmetics and other healthcare applications. Bioactive peptides were conjugated to the scaffolds via photoactivation reaction utilizing 488 nm visible light. In addition, the use of a photocleavable crosslinker enables dissociation of chemical moieties by 405 nm laser irradiation. The synthesis scheme enables optical control to attach and detach functional peptides in pre-patterned shapes. Using bone forming peptide (BFP), we demonstrate that calcium deposition by rat bone stromal cells can be directed on the scaffold. Using other signaling molecules and three-dimensional scaffolds, controlled differentiation of stem cells can be achieved by spatio-temporally specific irradiation of confocal microscope laser.


Assuntos
Colágeno/química , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Diferenciação Celular/fisiologia , Células Cultivadas , Ratos , Células-Tronco/citologia , Células-Tronco/fisiologia , Engenharia Tecidual
9.
Am J Trop Med Hyg ; 100(3): 643-646, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30628568

RESUMO

This study was conducted to find the burden of dengue virus (DENV) and Japanese encephalitis virus (JEV) among children under the age of 13, who presented with acute encephalitis syndrome at Mandalay Children Hospital in Myanmar in 2013. Molecular and serological investigations were performed on 123 cerebrospinal fluid (CSF) samples collected from these patients. By neutralization tests and/or virus isolation, four (3.3%) JEV- and one DENV-associated encephalitis cases (0.8%) were confirmed. Antibody titer against JEV Genotype 3 was the highest among the laboratory-confirmed JEV cases. One strain of DENV-1 with Genotype 1 was isolated from the CSF sample of the dengue encephalitis patient; this was similar to the virus circulating in the study area and neighboring countries. This study shows that flaviviruses are important pathogens causing encephalitis in Myanmar. Active disease surveillance, vector control, and vaccination programs should be enforced to reduce the morbidity and mortality caused by flavivirus encephalitis.


Assuntos
Dengue/complicações , Dengue/epidemiologia , Encefalite Japonesa/epidemiologia , Anticorpos Antivirais/líquido cefalorraquidiano , Criança , Pré-Escolar , Dengue/líquido cefalorraquidiano , Vírus da Dengue/genética , Encefalite Japonesa/líquido cefalorraquidiano , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Mianmar/epidemiologia , Testes de Neutralização , Filogenia
10.
Virus Res ; 247: 120-124, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29409678

RESUMO

An entomological surveillance of arboviruses was conducted in Myanmar in 2014. A total of 8357 Culex mosquito vectors were collected in the Mandalay area and virus isolation was done by using the mosquito cell line C6/36 E2. A total of eighteen strains of Culex flavivirus (CxFV) were isolated from Cx. tritaeniorhynchus, Cx. vishnui and Cx. fuscocephala. Like other insect-specific flaviviruses, CxFV can replicate only in mosquito cells but not in mammalian cells. These CxFV strains that were isolated in Japan from mosquitoes collected in Myanmar were closely related to the Wang Thong virus detected from Cx fusocephalus in Thailand and Cx.theileri flavivirus (CTFV) isolated from Cx. theileri mosquitoes in Portugal and Turkey. They encode a single open reading frame with 3357 amino acid residues. They have the characteristics of flaviviruses and have 95.62% amino acid identity with CTFV. This is the first report of CxFV in Myanmar with the characterized viral genome. This study illustrated that CxFV was circulating among the vectors of human pathogenic arboviruses in Myanmar but the impact of CxFV on other flaviviruses which are endemic in the study area still remains to be explored.


Assuntos
Culex/virologia , Flavivirus/genética , Genoma Viral , Mosquitos Vetores/virologia , Tropismo Viral , Animais , Monitoramento Epidemiológico , Flavivirus/classificação , Flavivirus/isolamento & purificação , Especificidade de Hospedeiro , Humanos , Mianmar , Fases de Leitura Aberta , Filogenia , Replicação Viral
11.
J Tissue Eng Regen Med ; 12(3): e1360-e1369, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28715113

RESUMO

Reproducing the features of the extracellular matrix is important for fabricating three-dimensional (3D) scaffolds for tissue regeneration. A collagen-like polypeptide, poly(Pro-Hyp-Gly), is a promising material for 3D scaffolds because of its excellent physical properties, biocompatibility, and biodegradability. In this paper, we present a novel photocrosslinked poly(Pro-Hyp-Gly) hydrogel as a 3D scaffold for simultaneous rat bone marrow stromal cell (rBMSC) encapsulation. The hydrogels were fabricated using visible-light photocrosslinking at various concentrations of methacrylated poly(Pro-Hyp-Gly) (20-50 mg/ml) and irradiation times (3 or 5 min). The results show that the rBMSCs encapsulated in the hydrogels survived 7 days of incubation. Calcium deposition on the encapsulated rBMSCs was assessed with scanning electron microscope observation, Alizarin Red S, and von Kossa staining. The most strongly stained area was observed in the hydrogel formed with 30 mg/ml of methacrylated poly(Pro-Hyp-Gly) with 5-min irradiation. These findings demonstrate that poly(Pro-Hyp-Gly) hydrogels support rBMSC viability and differentiation, as well as demonstrating the feasibility of using poly(Pro-Hyp-Gly) hydrogels as a cytocompatible, biodegradable 3D scaffold for tissue regeneration.


Assuntos
Cálcio/farmacologia , Células Imobilizadas/citologia , Colágeno/farmacologia , Reagentes para Ligações Cruzadas/farmacologia , Hidrogéis/farmacologia , Luz , Células-Tronco Mesenquimais/citologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Imobilizadas/efeitos dos fármacos , Colágeno/síntese química , Colágeno/química , Amarelo de Eosina-(YS)/química , Etanolaminas/química , Feminino , Hidrogéis/síntese química , Hidrogéis/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Metacrilatos/síntese química , Metacrilatos/química , Espectroscopia de Prótons por Ressonância Magnética , Pirrolidinonas/química , Ratos Wistar , Fatores de Tempo
12.
J Biomater Sci Polym Ed ; 28(14): 1480-1496, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28514893

RESUMO

Polyion complex (PIC) gel of poly(Pro-Hyp-Gly) was successfully fabricated by simply mixing polyanion and polycation derivatives of poly(Pro-Hyp-Gly), a collagen-like polypeptide. The polyanion, succinylated poly(Pro-Hyp-Gly), and the polycation, arginylated poly(Pro-Hyp-Gly), contain carboxy (pKa = 5.2) and guanidinium (pKa = 12.4) groups, respectively. Mixing the polyanion and the polycation at physiological pH (pH = 7.4) resulted in PIC gel. The hydrogel formation was optimum at an equimolar ratio of carboxy to guanidinium groups, suggesting that ionic interaction is the main determinant for the hydrogel formation. The hydrogel was successfully used for simultaneous rat bone marrow stromal cell encapsulation. The encapsulated cells survived and proliferated within the hydrogel. In addition, the cells exhibited different morphology in the hydrogel compared with cells cultured on a tissue culture dish as a two-dimensional (2D) control. At day one, a round morphology and homogeneous single cell distribution were observed in the hydrogel. In contrast, the cells spread and formed a fibroblast-like morphology on the 2D control. After three days, the cells in the hydrogel maintained their morphology and some of them formed multicellular aggregates, which is similar to cell morphology in an in vivo microenvironment. These results suggest that the PIC gel of poly(Pro-Hyp-Gly) can serve as a cytocompatible three-dimensional scaffold for stem cell encapsulation, supporting their viability, proliferation, and in vivo-like behavior.


Assuntos
Materiais Biocompatíveis/química , Colágeno/química , Células-Tronco Mesenquimais/química , Animais , Cápsulas , Sobrevivência Celular/efeitos dos fármacos , Colágeno/farmacologia , Géis , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Peso Molecular , Conformação Proteica em Folha beta , Ratos
13.
J Tissue Eng Regen Med ; 11(3): 869-876, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-25627868

RESUMO

Encapsulation of stem cells into a three-dimensional (3D) scaffold is necessary to achieve tissue regeneration. Prefabricated 3D scaffolds, such as fibres or porous sponges, have limitations regarding homogeneous cell distribution. Hydrogels that can encapsulate cells such as animal-derived collagen gels need adjustment of the pH and/or temperature upon cell mixing. In this report, we fabricated a poly-ion complex (PIC) hydrogel of chitosan and succinylated poly(Pro-Hyp-Gly) and assessed its effect on cell viability after encapsulation of rat bone marrow stromal cells. PIC hydrogels were obtained successfully with a concentration of each precursor as low as 3.0-3.8 mg/ml. The maximum gelation and swelling ratios were achieved with an equal molar ratio (1:1) of anionic and cationic groups. Using chitosan acetate as a cationic precursor produced a PIC hydrogel with both a significantly greater gelation ratio and a better swelling ratio than chitosan chloride. Ammonium succinylated poly(Pro-Hyp-Gly) as an anionic precursor gave similar gelation and swelling ratios to those of sodium succinylated poly(Pro-Hyp-Gly). Cell encapsulation was also achieved successfully by mixing rat bone marrow stromal cells with the PIC hydrogel simultaneously during its formation. The PIC hydrogel was maintained in the culture medium for 7 days at 37°C and the encapsulated cells survived and proliferated in it. Although it is necessary to improve its functionality, this PIC hydrogel has the potential to act as a 3D scaffold for cell encapsulation and tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Células Imobilizadas/citologia , Quitosana/farmacologia , Colágeno/farmacologia , Géis/farmacologia , Células-Tronco Mesenquimais/citologia , Ácido Succínico/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Cromatografia em Gel , Dicroísmo Circular , Feminino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier
14.
J Bone Miner Metab ; 35(4): 419-427, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27565972

RESUMO

Currently, the only available evidence for the efficacy of once-weekly 17.5 mg risedronate in preventing vertebral fractures was obtained in a 48-week study in Japan. We performed a 156-week prospective, longitudinal, observational study to determine the efficacy of the 17.5 mg risedronate in preventing vertebral fractures. We included Japanese patients with established osteoporosis who were older than 50 years and had radiographically confirmed vertebral fractures. The primary endpoint was the incidence of vertebral fractures every 24 weeks, with the final interval spanning 36 weeks. We also calculated the change in bone mineral density of the lumbar spine (L2-4 BMD) and urinary N-telopeptide of type I collagen (u-NTX), and assessed the incidence of adverse drug reactions and the drug adherence rate. Data from 241 patients were available for analysis of vertebral fracture prevention. The incidence rate of vertebral fractures decreased in a time-dependent manner (P = 0.0006; Poisson regression analysis). The risk ratio (fracture incidence per 100 person-years in the final 36 weeks versus that in the first 24 weeks) was 0.21 (95 % confidence interval 0.08-0.55). Compared to baseline values, L2-4 BMD increased by 6.41 % at 156 weeks, while u-NTX decreased by 36 % at 24 weeks and was maintained thereafter (P < 0.0001). The incidence rate of adverse drug reactions was 9.18 %. Drug adherence rates assessed every 4 weeks were over 90 %. Our results indicate that 156 weeks of treatment with once-weekly 17.5 mg risedronate effectively reduced the risk of vertebral fracture in Japanese patients with established osteoporosis older than 50 years.


Assuntos
Grupo com Ancestrais do Continente Asiático , Osteoporose/tratamento farmacológico , Ácido Risedrônico/administração & dosagem , Ácido Risedrônico/uso terapêutico , Fraturas da Coluna Vertebral/epidemiologia , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Colágeno Tipo I/urina , Esquema de Medicação , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Humanos , Incidência , Japão , Estudos Longitudinais , Vértebras Lombares/efeitos dos fármacos , Masculino , Osteoporose/complicações , Osteoporose/fisiopatologia , Osteoporose/urina , Cooperação do Paciente , Peptídeos/urina , Prevalência , Estudos Prospectivos , Ácido Risedrônico/efeitos adversos , Fatores de Risco , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/fisiopatologia , Fraturas da Coluna Vertebral/urina
15.
Clin Chem ; 61(4): 627-35, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25695852

RESUMO

BACKGROUND: Small molecules classified as haptens are generally measured by competitive immunoassay, which is theoretically inferior to noncompetitive sandwich immunoassay in terms of sensitivity and specificity. We created a method for developing sandwich immunoassays to measure haptens on the basis of antimetatype antibodies. METHODS: We generated antimetatype monoclonal antibodies against a hapten-antibody immunocomplex using an ex vivo antibody development system, the Autonomously Diversifying Library (ADLib) system. We selected 2 haptens, estradiol (E2) and 25-hydroxyvitamin D [25(OH)D], as analytes. Sandwich immunoassays for these 2 haptens were developed by use of a 96-well microtiter plate and a fully automated chemiluminescence analyzer, and the performances of these immunoassays were investigated. RESULTS: The developed assays exhibited sensitivity high enough to detect target haptens in serum samples. The limit of detection of the ELISA for E2 was 3.13 pg/mL, and that of the fully automated chemiluminescent enzyme immunoassay (CLEIA) system was 2.1 ng/mL for 25(OH)D. The cross-reactivity with immunoreactive derivatives was effectively improved compared with the competitive assay. The CVs for the sandwich ELISA for E2 were 4.2%-12.6% (intraassay) and 6.2%-21.8% (total imprecision). The CVs for the sandwich CLEIA for 25(OH)D were 1.0%-2.3% (intraassay) and 1.9%-3.5% (total imprecision). In particular, the sandwich CLEIA for 25(OH)D showed correlations of r = 0.99 with both LC-MS/MS and a commercially available (125)I RIA. CONCLUSIONS: Our method represents a potentially simple and practical approach for routine assays of haptens, including vitamins, hormones, drugs, and toxins.


Assuntos
Anticorpos Monoclonais , Estradiol/sangue , Haptenos/sangue , Imunoensaio/métodos , Vitamina D/análogos & derivados , Humanos , Imunoensaio/normas , Limite de Detecção , Sensibilidade e Especificidade , Vitamina D/sangue
16.
J Oleo Sci ; 63(12): 1303-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25452267

RESUMO

Water-based architectural paints commonly contain either mineral oil-based or silicone-based antifoams. Mineral oil-based antifoams generally reduce the gloss of paint films; thus, silicone-based antifoams are mainly used in the field of architectural paints. The relationship between the antifoaming performance and the particle size of hydrophobic silica for mineral oil-based antifoams was investigated and a novel mineral oil-based antifoam that provided a glossy surface to the paint films equivalent to the surface obtained with silicone-based antifoams and with excellent antifoaming performance compared to silicone-based antifoams was developed. The novel mineral oil-based antifoam exhibits better performance than silicon-based antifoam, and thus the former is a perfect alternative to the latter for use in architectural paints.


Assuntos
Antiespumantes/química , Óleo Mineral/química , Pintura , Dióxido de Silício/química , Interações Hidrofóbicas e Hidrofílicas , Pintura/análise , Tamanho da Partícula , Silicones , Propriedades de Superfície
17.
Biomater Sci ; 2(9): 1172-1185, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25485105

RESUMO

We demonstrate utilization of star-shaped polymers as high-density polymer brush coatings and their effectiveness to inhibit the adhesion of platelets and bacteria. Star polymers consisting of poly(2-hydroxyethyl methacrylate) (PHEMA) and/or poly(methyl methacrylate) (PMMA), were synthesized using living radical polymerization with a ruthenium catalyst. The polymer coatings were prepared by simple drop casting of the polymer solution onto poly(ethylene terephthalate) (PET) surfaces and then dried. Among the star polymers prepared in this study, the PHEMA star polymer (star-PHEMA) and the PHEMA/PMMA (mol. ratio of 71/29) heteroarm star polymer (star-H71M29) coatings showed the highest percentage of inhibition against platelet adhesion (78-88% relative to noncoated PET surface) and Escherichia coli (94-97%). These coatings also showed anti-adhesion activity against platelets after incubation in Dulbecco's phosphate buffered saline or surfactant solution for 7 days. In addition, the PMMA component of the star polymers increased the scratch resistance of the coating. These results indicate that the star-polymer architecture provides high polymer chain density on PET surfaces to prevent adhesion of platelets and bacteria, as well as coating stability and physical durability to prevent exposure of bare PET surfaces. The star polymers provide a simple and effective approach to preparing anti-adhesion polymer coatings on biomedical materials against the adhesion of platelets and bacteria.

18.
Nat Rev Nephrol ; 10(5): 290-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24642801

RESUMO

The time and cost involved in bringing new drugs to the market hamper their approval. This problem is especially apparent in the case of renal diseases. Efficient drug research requires an a priori understanding of disease pathophysiology, target validation, rational and efficient drug discovery strategies and early testing of the physiological and pharmacological effects of the new agent in humans. Drug development initiated by academia benefits from international research networks and relies on internationally acceptable high-quality nonclinical data packages and bulk investigational drugs. Academics should, therefore, better understand pharmaceutical practice regulations and novel, efficient drug-development strategies. Many researchers remain unfamiliar with these areas and should collaborate with regulatory authorities to discover and validate surrogate markers for use in drug development, and to efficiently and effectively maximize the benefits and minimize the adverse effects of new drugs. The Japanese government and regulatory authorities have implemented a framework to encourage such collaborations; extension of this framework beyond its current reach is envisaged.


Assuntos
Descoberta de Drogas , Nefropatias/tratamento farmacológico , Biomarcadores , Ensaios Clínicos como Assunto , Países em Desenvolvimento , Desenho de Fármacos , Indústria Farmacêutica , Drogas em Investigação , Humanos , Japão , Falência Renal Crônica/terapia , Parcerias Público-Privadas , Doenças Raras/tratamento farmacológico , Diálise Renal/economia , Diálise Renal/tendências
19.
Cancer Res ; 73(1): 62-73, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23108144

RESUMO

Both innate and adaptive immunity are crucial for cancer immunosurveillance, but precise therapeutic equations to restore immunosurveillance in patients with cancer patients have yet to be developed. In murine models, α-galactosylceramide (α-GalCer)-loaded, tumor antigen-expressing syngeneic or allogeneic cells can act as cellular adjuvants, linking the innate and adaptive immune systems. In the current study, we established human artificial adjuvant vector cells (aAVC) consisting of human HEK293 embryonic kidney cells stably transfected with the natural killer T (NKT) immune cell receptor CD1d, loaded with the CD1d ligand α-GalCer and then transfected with antigen-encoding mRNA. When administered to mice or dogs, these aAVC-activated invariant NKT (iNKT) cells elicited antigen-specific T-cell responses with no adverse events. In parallel experiments, using NOD/SCID/IL-2rγc(null)-immunodeficient (hDC-NOG) mouse model, we also showed that the human melanoma antigen, MART-1, expressed by mRNA transfected aAVCs can be cross-presented to antigen-specific T cells by human dendritic cells. Antigen-specific T-cell responses elicited and expanded by aAVCs were verified as functional in tumor immunity. Our results support the clinical development of aAVCs to harness innate and adaptive immunity for effective cancer immunotherapy.


Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/transplante , Imunidade Adaptativa/imunologia , Animais , Apresentação Cruzada/imunologia , Cães , Citometria de Fluxo , Células HEK293 , Humanos , Imunidade Inata/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Transfecção
20.
Biopolymers ; 96(3): 302-15, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20939034

RESUMO

Collagens are widely used in medical applications, including as a scaffold for tissue regeneration. However, animal-derived collagens have several drawbacks, such as low thermal stability, nonspecific cell adhesion, antigenicity, and contamination with pathogenic substances. To overcome these problems, we chemically synthesized the collagen-like polypeptide, poly(prolyl-hydroxyprolyl-glycyl) (poly(Pro-Hyp-Gly)), which forms a collagen-like triple-helical structure and shows biodegradability and biocompatibility. Here, we designed a novel scaffold where fibronectin-derived Gly Arg-Gly-Asp-Ser (GRGDS) and Pro-His-Ser-Arg-Asn (PHSRN) peptides were simultaneously conjugated with poly(Pro-Hyp-Gly). We assessed cell adhesion and migration activities using NIH3T3 cells in the scaffold and stratification ofimmortalized rabbit corneal epithelial cells. Cell adhesion was enhanced in scaffolds with GRGDS, increased with increasing amounts of conjugated GRGDS, and was significantly higher than bovine type I atelocollagen but lower than bovine fibronectin. Interestingly, simultaneous conjugation of GRGDS and PHSRN synergistically enhanced cell migration. Scaffolds containing almost equal amounts of GRGDS and PHSRN showed significantly higher cell migration than bovine type I atelocollagen. Addition of free GRGDS completely inhibited cell migration on the scaffold, whereas addition of free PHSRN partially inhibited cell migration. These results suggest that GRGDS plays a definitive role, and PHSRN plays an additional role, in cell migration. Conjugation of GRGDS resulted in the same level of stratification of rabbit corneal epithelial cells compared with bovine type I atelocollagen and bovine fibronectin. Because the simultaneous conjugation of GRGDS and PHSRN on poly(Pro-Hyp-Gly) enhances cell adhesion, migration, and stratification, it may be a useful scaffold for tissue regeneration.


Assuntos
Movimento Celular , Colágeno/química , Peptídeos/química , Tecidos Suporte/química , Animais , Bovinos , Adesão Celular , Fibronectinas/química , Humanos , Camundongos , Células NIH 3T3 , Coelhos
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