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J Toxicol Sci ; 44(1): 1-11, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30626775


Cosmetics containing rhododendrol (RD) were voluntarily recalled after incidents of leukoderma related to their use. Users reported using up to five different RD-containing products by layered application. In this study, we investigated the effects of layered application, formulations, and their components on the skin permeation of cosmetics containing RD. Experiments were designed to simulate actual in-use conditions, such as varying application volumes, physical mixing of formulations, sequence of cosmetics application and time interval between applications, to establish their effect on the skin permeation of RD. Milk and lotion RD-containing cosmetics (2%), 1% aqueous RD, and preparations of formulation components were applied as the first or second layers as finite doses of 10 or 20 µL/cm2. Permeation experiments were performed through excised porcine ear skin using Franz diffusion cells with an effective diffusion area of 1.77 cm2. Cosmetics applied by layered application exhibited lower skin permeation of RD compared with a single application despite having the same application dose. High initial volume (20 µL at 0 or 5 sec) did not exhibit any significant reduction in the permeation of RD. Formulations and their components caused varying reductions in RD permeation, probably due to changes in thermodynamic activity of the active component. Layered application, formulation components, application volume, time interval and sequence of application had significant influences on the skin permeation of the active component. Moreover, this study established a method of investigating the influence of formulations and their components on the skin permeation of actives after layered application.

Butanoles/administración & dosificación , Cosméticos/administración & dosificación , Absorción Cutánea , Administración Cutánea , Animales , Butanoles/química , Composición de Medicamentos , Técnicas In Vitro , Piel/metabolismo , Porcinos
J Nutr Sci Vitaminol (Tokyo) ; 64(3): 209-214, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29962432


The association between advanced age and the thiamine concentration has not been conclusively determined. A recent report from Japan showed that more than half of nursing home elderly residents at an institution had a low whole-blood thiamine concentration (<20 ng/mL). Therefore, a high incidence of low thiamine concentrations among hospitalized elderly has been anticipated in the Japanese population but never investigated. We evaluated the whole thiamine concentration in newly hospitalized elderly patients (≥65 y old) with infectious diseases. Evaluations were performed on admission and at days 6-8 of hospitalization with liquid chromatography tandem mass spectrometry (LC/MS/MS). As a result, we enrolled a total of 471 patients from September 2015 to December 2016. The median thiamine concentration was 46 ng/mL (IQR, 37-58 ng/mL). Only 7 patients (1%) had thiamine concentrations below 20 ng/mL (66 nmol/L) on admission. Five of these patients were bedridden and unable to eat food by themselves, and the other two patients used loop diuretics for chronic heart failure. The thiamine concentration declined in most patients (84%) at days 6-8 of admission, regardless of their dietary intake during hospitalization. In conclusion, a low thiamine concentration was not prevalent among newly hospitalized elderly patients with infectious diseases. However, the thiamine concentration significantly decreased during the 6-8 d of hospitalization.

Envejecimiento/sangre , Hospitalización , Tiamina/sangre , Anciano , Anciano de 80 o más Años , Femenino , Hospitales Comunitarios/estadística & datos numéricos , Humanos , Japón/epidemiología , Masculino , Deficiencia de Tiamina/epidemiología
J Hum Genet ; 63(1): 55-62, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29167552


ETS proto-oncogene 1, transcription factor (ETS1) is involved in various immune responses. Genome-wide association studies on systemic lupus erythematosus in Chinese populations identified the association of ETS1 polymorphism in 3' untranslated region, rs1128334A, which was associated with lower ETS1 expression. In view of substantial sharing of susceptibility genes across multiple autoimmune diseases, we examined whether ETS1 is associated with a rare autoimmune rheumatic disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Association of rs1128334 was tested in 466 Japanese patients with AAV and 1099 healthy controls by logistic regression analysis under the additive model. AAV patients were classified into 285 microscopic polyangiitis (MPA), 92 granulomatosis with polyangiitis (GPA), 56 eosinophilic GPA, and 33 unclassifiable AAV, according to the European Medicines Agency (EMEA) algorithm. Among the patients, 376 were positive for MPO-ANCA and 62 for PR3-ANCA. When the patients were classified according to the EMEA classification, rs1128334A allele was significantly increased in GPA (P = 0.0060, P c = 0.030, odds ratio (OR), 1.54; 95% confidence interval (CI), 1.13-2.10). With respect to the ANCA specificity, significant association was observed in PR3-ANCA positive AAV (P = 0.0042, P c = 0.021, OR, 1.72; 95% CI, 1.19-2.49). In conclusion, ETS1 polymorphism was suggested to be associated with GPA and PR3-ANCA positive AAV in a Japanese population.

Regiones no Traducidas 3' , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/genética , Granulomatosis con Poliangitis/genética , Polimorfismo Genético , Proteína Proto-Oncogénica c-ets-1/genética , Grupo de Ascendencia Continental Asiática , Femenino , Humanos , Japón , Masculino
Extremophiles ; 21(5): 903-917, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28688056


The redox-responsive regulator SurR in the hyperthermophilic archaea Pyrococcus furiosus and Thermococcus kodakarensis binds to the SurR-binding consensus sequence (SBS) by responding to the presence of elemental sulfur. Here we constructed a surR gene disruption strain (DTS) in T. kodakarensis, and identified the genes that were under SurR control by comparing the transcriptomes of DTS and parent strains. Among these genes, transcript levels of ferredoxin:NADP+ oxidoreductases 1 and 2 (FNOR1 and FNOR2) genes displayed opposite responses to surR deletion, indicating that SurR repressed FNOR1 transcription while enhancing FNOR2 transcription. Each promoter region contains an SBS upstream (uSBS) and downstream (dSBS) of TATA. In addition to in vitro binding assays, we examined the roles of each SBS in vivo. In FNOR1, mutations in either one of the SBSs resulted in a complete loss of repression, indicating that the presence of both SBSs was essential for repression. In FNOR2, uSBS indeed functioned to enhance gene expression, whereas dSBS functioned in gene repression. SurR bound to uSBS2 of FNOR2 more efficiently than to dSBS2 in vitro, which may explain why SurR overall enhances FNOR2 transcription. Further analyses indicated the importance in the distance between uSBS and TATA for transcriptional activation in FNOR2.

Proteínas Arqueales/metabolismo , Ferredoxina-NADP Reductasa/metabolismo , Regulación de la Expresión Génica Arqueal , Thermococcus/genética , Factores de Transcripción/metabolismo , Proteínas Arqueales/genética , Ferredoxina-NADP Reductasa/genética , Oxidación-Reducción , Thermococcus/enzimología , Factores de Transcripción/genética , Activación Transcripcional
J Infect Chemother ; 19(6): 1047-52, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23715827


The transmission of multidrug-resistant organisms (MDROs) is an emerging problem in acute healthcare facilities. To reduce this transmission, we introduced intensive infection control team (ICT) activities and investigated the impact of their introduction. This study was conducted at a single teaching hospital from 1 April 2010 to 31 March 2012. During the intervention period, all carbapenem use was monitored by the ICT, and doctors using carbapenems inappropriately were individually instructed. Information related to patients with newly identified MDROs was provided daily to the ICT and instructions on the appropriate infection control measures for MDROs were given immediately with continuous monitoring. The medical records of newly hospitalized patients were reviewed daily to check previous microbiological results and infection control intervention by the ICT was also performed for patients with a previous history of MDROs. Compared with the pre-intervention period, the antimicrobial usage density of carbapenems decreased significantly (28.5 vs. 17.8 defined daily doses/1000 inpatient days; p < 0.001) and the frequency of use of sanitary items, especially the use of aprons, increased significantly (710 vs 1854 pieces/1000 inpatient days; p < 0.001). The number of cases with hospital-acquired MRSA (0.66 vs. 0.29 cases/1000 inpatient days; p < 0.001), hospital-acquired drug-resistant Pseudomonas aeruginosa (0.23 vs. 0.06 cases/1000 inpatient days; p = 0.006) and nosocomial Clostridium difficile-associated disease (0.47 vs. 0.11 cases/1000 inpatient days; p < 0.001) decreased significantly during the intervention period. Our study showed that proactive and continuous ICT interventions were effective for reduction of MDRO transmission.

Infecciones por Clostridium/prevención & control , Infección Hospitalaria/prevención & control , Control de Infecciones/estadística & datos numéricos , Infecciones por Pseudomonas/prevención & control , Infecciones Estafilocócicas/prevención & control , Antibacterianos/farmacología , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/microbiología , Clostridium difficile/efectos de los fármacos , Clostridium difficile/aislamiento & purificación , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Humanos , Control de Infecciones/métodos , Japón/epidemiología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología