2 research outputs found
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
Two-Step Preparation of Protein-Decorated Biohybrid Quantum Dot Nanoparticles for Cellular Uptake
Decoration of nanoparticles with specific molecules such as antibodies, peptides, and proteins that preserve their biological properties is essential for the recognition and internalization of their specific target cells. Inefficient preparation of such decorated nanoparticles leads to nonspecific interactions diverting them from their desired target. We report a simple two-step procedure for the preparation of biohybrid nanoparticles containing a core of hydrophobic quantum dots coated with a multilayer of human serum albumin. These nanoparticles were prepared by ultra-sonication, crosslinked using glutaraldehyde, and decorated with proteins such as human serum albumin or human transferrin in their native conformations. These nanoparticles were homogeneous in size (20–30 nm), retained the fluorescent properties of quantum dots, and did not show a “corona effect” in the presence of serum. The uptake of transferrin-decorated quantum dot nanoparticles was observed in A549 lung cancer and SH-SY5Y neuroblastoma cells but not in non-cancerous 16HB14o- or retinoic acid dopaminergic neurons differentiated SH-SY5Y cells. Furthermore, digitoxin-loaded transferrin-decorated nanoparticles decreased the number of A549 cells without effect on 16HB14o-. Finally, we analyzed the in vivo uptake of these biohybrids by murine retinal cells, demonstrating their capacity to selectively target and deliver into specific cell types with excellent traceability.Fil: Traverso, Agata Noelia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; ArgentinaFil: Fragale, David JosĂ©. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; ArgentinaFil: Viale, Diego Luis. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; ArgentinaFil: Garate, Octavio Federico. Instituto Nacional de TecnologĂa Industrial; ArgentinaFil: Torres, Pablo Sebastian. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Ciencia y TecnologĂa "Dr. CĂ©sar Milstein". FundaciĂłn Pablo Cassará. Instituto de Ciencia y TecnologĂa "Dr. CĂ©sar Milstein"; ArgentinaFil: Valverde, GastĂłn. Universidad de Buenos Aires. Facultad de Medicina. Departamento de PatologĂa; ArgentinaFil: Berra, Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Departamento de PatologĂa; ArgentinaFil: Torbidoni, Ana Vanesa. Universidad "juan Agustin Maza". Vicerrectorado de InvestigaciĂłn, ExtensiĂłn y VinculaciĂłn.. Instituto Argentino de Veterinaria, Ambiente y Salud.; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Yakisich, Juan Sebastián. Hampton University; Estados UnidosFil: Grasselli, Mariano. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - La Plata. Instituto Multidisciplinario de BiologĂa Celular. Provincia de Buenos Aires. GobernaciĂłn. ComisiĂłn de Investigaciones CientĂficas. Instituto Multidisciplinario de BiologĂa Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de BiologĂa Celular; ArgentinaFil: Radrizzani, MartĂn. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; Argentin