RESUMEN
Patient engagement for patient safety is emphasized in recent years. Therefore, the Committee on Quality and Patient Safety of the Japan Primary Care Association developed a Japanese Patient Engagement Promotion Training (J-PEPT) course. J-PEPT promotes to facilitate the implementation of PE strategies and contributes to nationwide dissemination for patient safety.
RESUMEN
We have identified a novel series of ring-fused pyrazole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <1nM) as well as excellent cellular activity against mixed lymphocyte reaction (MLR) (IC(50)s <1nM).
Asunto(s)
Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/síntesis química , Pirroles/química , Adenosina Trifosfato/química , Sitios de Unión , Simulación por Computador , Cristalografía por Rayos X , Enlace de Hidrógeno , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Pirroles/síntesis química , Pirroles/farmacología , Relación Estructura-ActividadRESUMEN
We have described the synthesis, enzyme inhibitory activity, structure-activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <10nM) for Lck kinase inhibition.
Asunto(s)
Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/síntesis química , Pirroles/síntesis química , Adenosina Trifosfato/química , Sitios de Unión , Simulación por Computador , Cristalografía por Rayos X , Enlace de Hidrógeno , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Pirroles/química , Pirroles/farmacología , Relación Estructura-ActividadRESUMEN
To search for the pruritogen of atopic dermatitis, a characteristic symptom in atopic dermatitis patients, we examined interleukin-31 (IL-31) mRNA expression in NC/Nga mice as an animal model of atopic dermatitis. The expression of IL-31 mRNA in the skin of NC/Nga mice with scratching behavior was significantly higher than that in NC/Nga mice without scratching behavior. Our findings suggest that IL-31 may participate in the cause of itch sensation and promote scratching behavior in NC/Nga mice with atopic dermatitis.
Asunto(s)
Dermatitis Atópica/genética , Expresión Génica/genética , Interleucinas/genética , Animales , Masculino , Ratones , Ratones Endogámicos , Prurito/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Piel/metabolismo , Piel/patología , Organismos Libres de Patógenos Específicos , Transcripción Genética/genéticaRESUMEN
Pigments extracted from natural products are widely used for food coloration in Japan. An investigation concerning the photo-mutagenicity and photo-carcinogenicity of frequently used colorants in Japan was performed. Colorants examined were from Laccifer lacca (lac-color), Coccus cacti (cochineal-color), Carthamus tinctorius (carthamus yellow), Gardenia augusta (gardenia yellow and gardenia blue), Monascus anka and Monascus purpureus (monascus red), the skin of Vitis vinifera and Vitis labrusca (grape-skin color), Tamarindus indica (tamarind brown) and Beta vulgaris (beet red). No significant increase in bacterial mutation was found when Salmonella typhimurium TA98, TA100 and TA102 were simultaneously treated with colorants and subjected to UVA irradiation for 30 min. When colorant solutions were subjected to UVA irradiation for 4 h, irradiated solutions containing lac-color became slightly mutagenic toward S.typhimurium TA98 without metabolic activation. A decrease in cell survival resulted when WTK-1 cells were subjected to UVA irradiation for 60 min in the presence of purpurin at 1 mg/ml. Delayed cytotoxicity was also observed following 24 h incubation in fresh medium of samples that were subjected to UVA irradiation for 60 min in the presence of colorant (carthamus yellow, grape-skin color, gardenia blue, cochineal-color, monascus red or purpurin).
