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

Amifostine Protection Against Mitomycin-induced Chromosomal Breakage in Fanconi Anaemia Lymphocytes

Fanconi anaemia (FA) is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS) imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF) on basal and mitomycin C (MMC)-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronuclei count was higher among FA patients than healthy subjects. Pre-treatment with AMF significantly inhibited micronucleation induced by MMC in healthy subjects (23.4 ± 4.0 – MMC vs 12.3 ± 2.9 – AMF →MMC) MN/1000CB, p < 0.01, one way ANOVA) as well as in FA patients (80.0 ± 5.8 – MMC vs 40.1 ± 5.8 – AMF →MMC) MN/1000CB, p < 0.01, ANOVA). Release of ROS by peripheral blood mononuclear cells treated with AMF →MMC and measured by chemoluminometry showed that AMF-protection was statistically higher among FA patients than in healthy individuals. Based on these results we suggest that AMF prevents chromosomal breakage induced by MMC, probably by its antioxidant effect

Adsorción de fósforo en algunos suelos argentinos : 1-condiciones experimentales e isotermas de adsorción

p.165-174Se estudió la influencia sobre los procesos de adsorción de las siguientes condiciones experimentales: relación suelo-solución, tiempo de agitación, tratamientos con cloroformo y temperatura. La mayor adsorción correspondió a la menor relación suelo: solución, al mayor tiempo de agitación, al tratamiento sin cloroformo y a la mayor temperatura. Siguiendo la técnica de Ozanne y Shaw, se efectuaron las curvas de adsorción de 16 suelos y se calculó la capacidad reguladora de fosfatos de los mismos. Los datos experimentales obtenidos presentaron mejor ajuste con las ecuaciones de Freundlich y Temkin que con la de Langmuir

Anencefalia: um estudo epidemiológico de treze anos na cidade de Pelotas Anencephaly: thirteen years of epidemiological study in Pelotas city

A anencefalia é a forma letal mais comum dentre as anomalias do SNC. Apesar dos casos isolados, a anencefalia parece ser de causa multifatorial. Este defeito ocorre devido a um não fechamento da extremidade anterior do sulco neural. Este trabalho, que tem como objetivo estudar a freqüência, a etiologia e os fatores predisponentes desta malformação, é um estudo de caso-controle de base populacional que abrange todos os nascimentos ocorridos nas cinco maternidades da cidade de Pelotas, durante o período de 1º de janeiro de 1990 a 31 de dezembro de 2002.<br>The anencephaly is the most common lethal form among the CNS anomalies. Although isolated cases occur, the anencephaly seems to be caused by multiple factors. This malformation result from closure defects of the anterior neural sulk, during embryonic development. The aim of this study was analyze the frequency, etiology, and the risk factors of this congenital malformation. This population-based case-control study range all births occurred in five maternities of Pelotas city from January, 1st 1990 to December, 12 2002