Sitagliptin ameliorates oxidative stress in experimental diabetic nephropathy by diminishing the miR-200a/Keap-1/Nrf2 antioxidant pathway.

BACKGROUND: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor used in type 2 diabetes therapy, has demonstrated protective effects in diabetic chronic kidney disease, in part due to its pleiotropic actions. However, its potential direct effects on the kidney are still not completely defined. Here, by means of proteomics and miRNA profiling, we have further unveiled the role of sitagliptin in oxidative stress, as well as the underlying mechanisms. METHODS: Renal cortex samples from 9-month-old wild-type (Wistar), type II diabetic Goto-Kakizaki (GK) and sitagliptin-treated GK rats (GK+Sita) (10 mg kg-1 per day) were subjected to quantitative miRNA transcriptomic array, immunohistochemistry and Western blot studies. Renal GK and GK+Sita samples were also analyzed by differential in-gel electrophoresis. Bioinformatic tools were used to find out the relationships between altered proteins and related miRNA expression. Studies were also carried out in cultured tubular cells to confirm in vivo data. RESULTS: Diabetic GK rats exhibited proteinuria, renal interstitial inflammatory infiltrates and fibrosis, which improved by 20 weeks of sitagliptin treatment. Proteomic analysis of diabetic GK and Wistar rats showed a differential expression of 39 proteins mostly related to oxidative stress and catabolism. In addition, 15 miRNAs were also significantly altered in GK rats. CONCLUSION: Treatment with sitagliptin was associated with modulation of antioxidant response in the diabetic kidney, involving a downregulation of miR-200a, a novel Keap-1 inhibitor and miR-21, coincidentally with the clinical and the morphological improvement. These data further support the concept that DPP-4 inhibitors could exert a direct reno-protective effect in patients with diabetic nephropathy.

Diez años desde la implementación del RIS PACS de la Clínica Alemana de Santiago: impacto de la tomografía computarizada en el uso y disponibilidad de archivo / Ten years since the implementation of Clínica Alemana of Santiago's RIS PACS: the impact of computed tomography in the use and availability of storage

Abstract. RIS PACS systems have become indispensable for managing, distributing and archiving digital images. This study evaluated the impact of Computed Tomography in the Clínica Alemana of Santiago's PACS image service. The PACS database was reviewed using IMPAX BI software, and 2,267,683 studies between 2005 and 2014 were examined. Computed Tomography examinations made up 10.67% of the studies archived in PACS, but its weight in TB is 50.10% of the total. The impact of the studies of Computed Tomography were not properly dimensioned or anticipated, which has impacted on the expected availability for one year online studies. This study has adequately assessed the impact of Computed Tomography in PACS’ storage availability, and how it should be considered when planning the implementation of a PACS.

Resumen. Los sistemas RIS PACS se han vuelto indispensables para el manejo de las imágenes digitales, su distribución y archivo. Esta investigación evaluó el impacto de la tomografía computarizada en el PACS del servicio de imágenes de la Clínica Alemana de Santiago. Se revisó la base de datos del PACS a través de la herramienta de software IMPAX BI, de los 2.267.683 estudios del período 2005-2014. Los exámenes de tomografía computarizada representan el 10,67% de los estudios archivados en el PACS, pero su peso en TB es el 50,10% del total. El impacto de los estudios de tomografía computarizada no se ha dimensionado ni previsto adecuadamente, lo que ha impactado en la disponibilidad esperada para los estudios de un año on line. Este estudio ha permitido valorar adecuadamente el impacto de la tomografía computarizada en la disponibilidad del PACS, y cómo debe ser considerado al planificar la implementación de un PACS.

Safety and efficacy of gadofosveset-enhanced MR angiography for evaluation of pedal arterial disease: multicenter comparative phase 3 study.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of gadofosveset, a gadolinium-based albumin-binding MRI contrast agent, in patients with pedal arterial disease. SUBJECTS AND METHODS: A total of 185 adult patients with known or suspected pedal arterial disease were randomized in a group receiving 0.03 mmol/kg and a group receiving 0.05 mmol/kg of gadofosveset for MR angiography of the pedal arteries. Gadofosveset-enhanced and unenhanced time-of-flight MR angiograms were compared with conventional angiograms, the standard of reference, for the presence of vascular stenosis. All patients underwent drug safety analysis. RESULTS: For each of three blinded readers, the specificity (21-35%) of gadofosveset-enhanced MR angiography was a statistically significant (p < 0.010) improvement over that of unenhanced MR angiography in the detection of clinically significant (> 50%) stenosis. The sensitivities of the two techniques were similar. For all blinded readers of MR angiograms, sensitivity, specificity, and accuracy were higher with use of the 0.03-mmol/kg dose of gadofosveset than with the 0.05-mmol/kg dose. In the 0.03-mmol/kg group, 28% of patients reported a total of 50 adverse events, 96% of which were reported as mild or moderate. In the 0.05-mmol/kg group, 28% of patients reported a total of 55 adverse events, 98% of which were reported as mild or moderate. No patients died; one patient left the study because of myocardial infarction considered unrelated to the study drug. CONCLUSION: Because of markedly better efficacy than no contrast agent and a minimal and transient side-effect profile, 0.03 mmol/kg of gadofosveset was found safe and effective for MR angiography of patients with pedal arterial disease.

Head size and intelligence, learning, nutritional status and brain development. Head, IQ, learning, nutrition and brain.

This multifactorial study investigates the interrelationships between head circumference (HC) and intellectual quotient (IQ), learning, nutritional status and brain development in Chilean school-age children graduating from high school, of both sexes and with high and low IQ and socio-economic strata (SES). The sample consisted of 96 right-handed healthy students (mean age 18.0 +/- 0.9 years) born at term. HC was measured both in the children and their parents and was expressed as Z-score (Z-HC). In children, IQ was determined by means of the Wechsler Intelligence Scale for Adults-Revised (WAIS-R), scholastic achievement (SA) through the standard Spanish language and mathematics tests and the academic aptitude test (AAT) score, nutritional status was assessed through anthropometric indicators, brain development was determined by magnetic resonance imaging (MRI) and SES applying the Graffar modified method. Results showed that microcephalic children (Z-HC < or = 2 S.D.) had significantly lower values mainly for brain volume (BV), parental Z-HC, IQ, SA, AAT, birth length (BL) and a significantly higher incidence of undernutrition in the first year of life compared with their macrocephalic peers (Z-HC > 2S.D.). Multiple regression analysis revealed that BV, parental Z-HC and BL were the independent variables with the greatest explanatory power for child's Z-HC variance (r(2) = 0.727). These findings confirm the hypothesis formulated in this study: (1) independently of age, sex and SES, brain parameters, parental HC and prenatal nutritional indicators are the most important independent variables that determine HC and (2) microcephalic children present multiple disorders not only related to BV but also to IQ, SA and nutritional background.

Tennis leg: clinical US study of 141 patients and anatomic investigation of four cadavers with MR imaging and US.

PURPOSE: To evaluate the ultrasonographic (US) findings in patients with a referring diagnosis of tennis leg and to explore the relative importance of the plantaris tendon and gastrocnemius muscle in the pathogenesis of this condition. MATERIALS AND METHODS: A cadaveric study was performed to outline the normal anatomy of the posterosuperficial compartment of the calf. Magnetic resonance (MR) imaging and US were performed, followed by gross anatomic correlation. US findings in 141 patients referred with a clinical diagnosis of tennis leg were retrospectively reviewed by means of consensus of two radiologists. Images were analyzed with respect to the integrity of the lower-leg musculotendinous units, presence of fluid collection, and deep venous thrombosis. RESULTS: MR imaging and US enabled distinction of the musculotendinous unit of the plantaris from the remaining muscles of the lower extremity in cadaveric specimens. US findings in the 141 patients included rupture of the medial head of the gastrocnemius muscle in 94 patients (66.7%), fluid collection between the aponeuroses of the medial gastrocnemius and soleus muscles without muscle rupture in 30 patients (21.3%), rupture of the plantaris tendon in two patients (1.4%), and partial rupture of the soleus muscle in one patient (0.7%). Deep venous thrombosis was seen in isolation in 14 patients (9.9%). CONCLUSION: In patients with clinical findings of tennis leg who undergo US, abnormalities of the medial gastrocnemius muscle appear to be more common than those of the plantaris tendon.

Nutritional status, brain development and scholastic achievement of Chilean high-school graduates from high and low intellectual quotient and socio-economic status.

The objective of the present study was to investigate the inter-relationships between nutritional status (past and current nutrition), brain development, and scholastic achievement (SA) of Chilean high-school graduates from high and low intellectual quotient (IQ) and socio-economic status (SES) (mean age 18.0 (SD 0.9) years). Results showed that independently of SES, high-school graduates with similar IQ have similar nutritional, brain development and SA variables. Multiple regression analysis between child IQ (dependent variable) and age, sex, SES, brain volume (BV), undernutrition during the first year of life, paternal and maternal IQ (independent variables) revealed that maternal IQ (P<0.0001), BV (P<00387) and severe undernutrition during the first year of life (P<0.0486), were the independent variables with the greatest explanatory power for child IQ variance (r2 0.707), without interaction with age, sex or SES. Child IQ (P<0.0001) was the only independent variable that explained both SA variance (r2 0.848) and academic aptitude test variance (r2 0.876) without interaction with age, sex or SES. These results confirm the hypotheses formulated for this study that: (1) independently of SES, high-school graduates with similar IQ have similar variables of nutritional status, brain development and SA; (2) past nutritional status, brain development, child IQ and SA are strongly and significantly inter-related. These findings are relevant in explaining the complex interactions between variables that affect IQ and SA and can be useful for nutritional and educational planning.