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 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 m 2), 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

Lipid composition and vitamin E concentration in cockerel meat

Two hundred and forty 30-week-old White Leghorn cockerels were distributed in a completely randomized 5 x 2 factorial arrangement, with five oil sources (sunflower, soybean, canola, linseed and fish) and two antioxidant levels (30 and 400 mg of vitamin E/kg). The aim of the study was to evaluate the inclusion of oil sources and vitamin E supplementation in the diet, on the concentration of total lipids, cholesterol and vitamin E in cockerel thigh and breast meat. The intake of fish and canola oil in the diet reduced (P<0.05) the content of total lipids in the thigh meat as compared to the other oil sources. The highest content of total lipids was observed (P<0.05) in the breast meat of cockerels fed on linseed oil. However, the contrary was observed when these cockerels were supplemented with 400 mg of vitamin E, showing an interaction between the oil source and vitamin E level. A diet containing soybean oil also caused an increase (P<0.05) in the content of total lipids and cholesterol in the thigh meat as compared to the use of fish and canola oil in the diet. Vitamin E deposition was greater (P<0.05) in the thigh meat of cockerels fed on canola oil than on fish oil. (C) 2003 Swiss Society of Food Science and Technology. Published by Elsevier Science Ltd. All rights reserved.36769770

Effect of oil sources and vitamin E levels in the diet on the composition of fatty acids in rooster thigh and chest meat

The aim of this study was to evaluate the inclusion of different oil sources and dietary supplementation with vitamin E on the composition of fatty acids in rooster meat. Two hundred and forty 30-week-old White Leghorn roosters were distributed in a completely randomized factorial arrangement of 5 x 2, using five oil sources (sunflower, soybean, canola, linseed and fish) and two levels of antioxidant (30 and 400 mg vitamin E kg(-1) of diet). The intake of fish and canola oil in the diet reduced (P < 0.05) the content of saturated and unsaturated fatty acids in the thigh meat. Amongst the unsaturated fatty acids in the thigh, the fish and canola oil reduced (P < 0.05) the level of omega6 fatty acid, with a consequent decrease in the ratio omega6:omega3. The diet with fish oil increased (P < 0.05) the content of C22:6omega3 in the thigh meat. The use of linseed oil resulted in a significant reduction of the ratio of omega6:omega3 fatty acid in the thigh. The use of soybean oil in the diet increased (P < 0.05) the content of saturated and unsaturated fatty acids in the thigh, specifically in the content of omega6. The inclusion of vitamin E increased the polyunsaturated fatty acids in the chest meat, such as C18:3omega3, C20:5omega3 and C22:6omega3. (C) 2004 Society of Chemical Industry.84767268

Evaluation of the ratio of omega 6 :omega 3 fatty acids and vitamin E levels in the diet on the reproductive performance of cockerels

Three hundred and twenty 30-week old White Leghorn cockerels were housed in individual cages and distributed in a completely randomized factorial design of 5 x 3, with five oil sources (sunflower, soybean, canola, linseed and fish/soybean) and three levels of antioxidant (30, 200 and 400 mg of vitamin E/kg). The aim of this study was to evaluate the effect of the ratio of omega6:omega3 fatty acids by the inclusion of different oil sources and of dietary supplementation with vitamin E on the reproductive performance of cockerels. The use of the fish/soybean combination determined the lowest total antioxidant status of the semen. However, the addition of vitamin E to the fish/soybean-oil-based diet resulted in a linear increase in semen volume, motility and sperm vigour in the 38th week and again in the 52nd week for motility and for sperm vigour and fertility rate in the periods from 50-53 and 41-53 weeks of age. The use of canola oil in the diet resulted in the highest fertility rate during 50-53 and 41-53 weeks of life. Animals receiving the soybean oil based diet showed the smallest fertility rate in the range from 50-53 weeks of age and concomitantly the highest level of cholesterol in the spermatozoa in the range from 47-51 weeks. An interaction between the vitamin E level and soybean oil was verified by the linear increase in motility and sperm vigour at 38 weeks of age. Later, the contrary was shown by a linear reduction in fertility in the periods from 44-46, 47-49 and 41-53 weeks of age. Cockerels that had been fed on the sunflower-oil-based diet showed the highest content of saturated fatty acids in the spermatozoa from 48-51 weeks. An interaction effect was observed between the vitamin E level and sunflower oil shown by a linear increase in the content of saturated fatty acids in the spermatozoa and a linear reduction in the C18:1omega9, C18:2omega6 and PUFA (C18:2omega6 + C20:4omega6) contents in the spermatozoa at 48-51 weeks and in sperm volume at 52 weeks of age.57642944

A linhaça (Linum usitatissimum) como fonte de ácido &#945;-linolênico na formação da bainha de mielina Flaxseed (Linum usitatissimum) as a source of &#945;-linolenic acid in the development of the myelin sheath

A linhaça (Linum usitatissimum) é uma semente oleaginosa que tem sido estudada por seus efeitos benéficos à saúde. É considerada um alimento funcional, pelo fato de ser uma fonte natural de fitoquímicos, e por conter o ácido graxo &#945;-linolênico (C18:3 n-3), que pode ser metabolicamente convertido nos ácidos docosaexahenóico (C22:6 n-3) e eicosapentaenóico (C20:5 n-3), sendo o primeiro essencial para o desenvolvimento do sistema nervoso central. Durante o crescimento do cérebro, há uma grande incorporação do ácido docosaexahenóico, que tem papel importante na formação de suas membranas celulares. Diante disto, esta comunicação visa a abordar os prováveis mecanismos pelos quais o ácido docosaexahenóico, proveniente do ácido &#945;-linolênico presente abundantemente na semente de linhaça, interfere na formação da bainha de mielina, assim como relatar a técnica mais adequada para visualização desta bainha.<br>Flaxseed is an oily seed that has been studied for its beneficial health effects. It is considered a functional food because it is a natural source of phytochemicals and contain the fatty acid &#945;-linolenic acid (C18:3 n-3) that can be metabolically converted into docosahexaenoic acid (C22:6 n-3) and eicosapentaenoic acid (C20:5 n-3). The former is essential for the development of the central nervous system. During brain growth, there is a great incorporation of docosahexaenoic acid which plays in important role in the formation of cell membranes. This communication intended to address the likely mechanisms by which docosahexaenoic acid originating from &#945;-linolenic acid, present in abundance in flaxseed, interferes in the formation of the myelin sheath and report the best method to see this structure

Effect of dietary organic selenium and zinc on the internal egg quality of quail eggs for different periods and under different temperatures

The objective of this study was to evaluate the internal quality of eggs of Japanese quails fed diets supplemented with chelated selenium and zinc. The experiment was carried out for 120 days, and 144 birds were divided in random blocks into four treatments (control; 0.3 ppm Se; 60 ppm Zn and 0.3 ppm Se + 60 ppm Zn). Ten, 14, 18, and 22 weeks after the beginning of lay, eggs were collected and stored under two different temperatures (environmental temperature or refrigeration) and for 10, 20, and 30 days. Eggs were analyzed for: Haugh units (HU), albumen height (AH), yolk index (YI), and albumen index (AI). Parameters were only statistically influenced by the interaction between dietary treatment and storage time. It was concluded that the addition of organic Se and Zn influenced internal egg quality when eggs were stored up to 20 days, independently of storage temperature, suggesting that the combined supplementation of organic Se and Zn improve internal egg quality and extend egg shelf life

An Optimized GD2-Targeting Retroviral Cassette for More Potent and Safer Cellular Therapy of Neuroblastoma and Other Cancers

<div><p>Neuroblastoma is the commonest extra cranial solid cancer of childhood. Despite escalation of treatment regimens, a significant minority of patients die of their disease. Disialoganglioside (GD2) is consistently expressed at high-levels in neuroblastoma tumors, which have been targeted with some success using therapeutic monoclonal antibodies. GD2 is also expressed in a range of other cancer but with the exception of some peripheral nerves is largely absent from non-transformed tissues. Chimeric Antigen Receptors (CARs) are artificial type I proteins which graft the specificity of a monoclonal antibody onto a T-cell. Clinical data with early CAR designs directed against GD2 have shown some promise in Neuroblastoma. Here, we describe a GD2-targeting CAR retroviral cassette, which has been optimized for CAR T-cell persistence, efficacy and safety.</p></div