RESUMEN
Diabetic kidney disease (DKD) is among the most common and serious complications of both type 1 and type 2 diabetes. In this study, we used KK/Ta-Ins2Akita (KK-Akita) mice as a model of DKD and KK/Ta (KK) mice as controls to identify novel factors related to the development/progression of DKD. Capillary electrophoresis coupled with mass spectrometry analysis revealed that circulating Asp (l-aspartic acid) levels in diabetic KK-Akita mice tend to be lower than those in control KK mice. Therefore, we evaluated the effect of Asp supplementation to prevent the progression of DKD in KK-Akita mice. Mice were divided into three groups: (a) untreated KK mice (Control group), (b) untreated KK-Akita mice (DKD group), and (c) treated (double-volume Asp diet) KK-Akita mice (Tx group). Kidney sections were stained with fluorescein isothiocyanate-labeled lectins, wheat germ agglutinin (WGA), and anti-endothelial nitric oxide synthase (eNOS) antibody for evaluation of endothelial surface layer (ESL) and NO synthesis. The mesangial area and glomerular size in the DKD group were significantly larger than those in the Control group; however, there was no significant difference in those between the DKD and Tx groups. Albuminuria, the ratio of foot process effacement, and thickness of glomerular basement membrane in the Tx group were significantly lower than those in the DKD group. Furthermore, the expression levels of glomerular WGA and microvascular eNOS in the Tx group improved significantly and approached the level in the Control group. In conclusion, the improvement of albuminuria in the Tx group may be caused by the reduction of oxidative stress in the kidneys, which may lead to the subsequent improvement of glomerular ESL.
Asunto(s)
Albuminuria/dietoterapia , Ácido Aspártico/administración & dosificación , Nefropatías Diabéticas/dietoterapia , Suplementos Dietéticos , Albuminuria/sangre , Albuminuria/genética , Albuminuria/patología , Animales , Ácido Aspártico/sangre , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Modelos Animales de Enfermedad , Endotelio/patología , Endotelio/ultraestructura , Femenino , Membrana Basal Glomerular/patología , Membrana Basal Glomerular/ultraestructura , Humanos , Masculino , Ratones , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Óxido Nítrico Sintasa de Tipo III/análisis , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés OxidativoRESUMEN
An 80-year-old female visited our hospital with the chief complaint of lower abdominal pain and diarrhea. She was diagnosed to have rectal cancer. Hartmann operation was performed and curative resection was successfully achieved. Postoperative stage was III according to the classification of the Japanese Society for Cancer of the Colon and Rectum(The 7th Edition). She was treated with oral tegafur(UFT 300mg/body/day)as adjuvant chemotherapy for 6 months. Paraaortic lymph node metastasis and local recurrence were diagnosed by abdominal CT 1 year after the surgery. Her performance status score was 0. She was treated with modified FOLFOX6 chemotherapy combined with bevacizumab. Abdominal CT revealed a partial response after 5 courses. She experienced grade 2 leukocyopenia, grade 3 neutropenia, grade 2 proteinuria and grade 2 hypertension.