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

Cromatografía de Pfaiffer en el análisis de suelos de sistemas productivos

The Pfaiffer chromatography is a qualitative analysis technique that can be used in soils,composts and biofertilizers, being able to quickly observe the relationship between microorganisms, organic matter and minerals, as elements that compose them. For the agricultural producer,it is important to know the conditions of the soil or supplies that he uses to obtain better results in his crops. The objective of the work was to perform Pfaiffer chromatography to analyze the soils of productive systems and compare some qualitative characteristics. The soil samples were taken at random from different plots, the first one with conventional agronomic management, the next one from a land with temporary production and the last one from an organic production system, were analyzed by Pfaiffer chromatography separately. The chromatograms were interpreted, being able to observe that the three types of soil provide the characteristics of the farming system to which they belong. Keywords:chromatograms, conventional, organic, temporalLa cromatografía de Pfaiffer es una técnica de análisis cualitativo que se puede usar en suelos, compostas y biofertilizantes, pudiendo observar rápidamente la relación que guardan los microorganismos, la materia orgánica y los minerales, como elementos que los componen. Para el productor agrícola es importante saber las condiciones del suelo o insumos que utiliza para obtener mejores resultados en sus cultivos. El objetivo del trabajo, fue realizar la cromatografía de Pfaiffer para analizar los suelos de sistemas productivos y comparar algunas características cualitativas. Las muestras de suelo fueron tomadas al azar de diferentes parcelas, el primero con manejo agronómico convencional, el siguiente de un terreno con producción de temporal y el último de un sistema de producción orgánico, fueron analizados mediante la cromatografía de Pfaiffer por separado. Se interpretaron los cromatogramas, pudiendo observar que los tres tipos de suelo proporcionan las características propias del sistema de labranza a que pertenecen. Palabras clave: cromatogramas, convencional, orgánico, tempora

Origin and evolution of tomato production Lycopersicon esculentum in México

ABSTRACT: Lycopersicon esculentum known as tomato, although has an Andean origin is a contribution of Mexico to the world is, being the first agricultural product to be exported. This research aimed to review the literature in relation to the origin and evolution of the production of tomato in Mexico within the historical development of the country. In ancient times, the tomato was cultivated in milpas (open field) and chinampas (artificial islands for riparian agriculture) using sustainable methods. Spanish colonizers showed the tomato to the rest of the world and diversified its uses. In independent Mexico, haciendas and railroads integrated the different farming regions. Production decreased during the Mexican revolution, and with land reform, the milpa returned. During the Green Revolution (1970), Sinaloa stood out, with the separation of two systems, subsistence, and modern with technology programs. Biotechnological development (1990) emerged parallel to organic production. So actually with this system, we could return to more sustainable pre-Hispanic ecological principles with less environmental impact

Bacillus subtilis como probiótico en avicultura: aspectos relevantes en investigaciones recientes

The present article is a compilation of papers that show the use of probiotics as an alternative to the use of antibiotics as growth promoters. The benefits of Basillus subtilis had been found in a wide variety of environments and their use as a probiotic has been extensively studied. It has been shown that B. subtilis as a probiotic is of safe use in the feeding broiler without negative effects on the environment. Others of the relevant characteristics of B. subtilis are their action on the stability of the intestinal microbial by reducing the presence of E. coli, Salmonella, and Coccidia, favoring the increase of beneficial microorganisms and improving immunity by increasing IgA and IgG. Recent research has shown that B. subtilis contributes to the reduction of levels of ammonia in excreta, the production of antioxidant substances and the increase of digestibility because of the equilibrium of the intestinal ecology of birds, it has also been found that xylanases producing B. subtilis have a similar effect to antibiotics in the small intestine. Knowing the B, subtilis as probiotic represents to improve productive parameters and sanitary conditions of the birds.El presente artículo es una recopilación de trabajos donde se observa el uso de los probióticos como alternativa al uso de antibióticos como promotores del crecimiento. Se revisaron las bondades del Basillus subtillis y su uso como probiótico, encontrado en una gran variedad de ambientes. Se ha mostrado que el B. subtilis como probiótico es seguro para usar en la alimentación de las aves sin efectos negativos en el medio ambiente. Otra de la característica relevante del B. subtilis es su acción en la estabilidad de la microbiaota intestinal al disminuir la presencia de E. Coli, Salmonelas y coccidias, favoreciendo el incremento de microorganismos benéficos y la inmunidad mediante el incremento de IgA e IgG. En investigaciones recientes se ha encontrado que el B. subtilis contribuye en la reducción de niveles de amoniaco en excretas, producción de sustancias antioxidantes y el aumento de la digestibilidad como consecuencia del equilibrio de la ecología intestinal de las aves. Además, también se ha encontrado que las xilanasas que producen los B. subtilis tienen un efecto similar a los antibióticos en intestino delgado. Conocer al B. subtilis como probiótico representa mejorar parámetros productivos y condiciones sanitarias de las aves

A proximal chemical analysis in craft beer solid waste, and its acceptance in sows

ABSTRACT A proximal chemical analysis on organic solid waste was performed from three types of craft beer and its acceptance in the feeding of sows was detected. To determine the humidity, a stove was used at 105 °C for 24 hours, the ethereal extract was determined using a Soxhlet equipment and ethyl ether as solvent, the determination of ash content was made by calcination in a muffle at 700 °C; for crude fiber analysis, acid digestion with 0.2 N sulfuric was used, the crude protein was determined using a Kjedahl equipment in order to analyze the total nitrogen, the nitrogen-free extract, was determined by the difference of 100 % minus the addition of moisture, ash, fat, protein, and fiber. The total of digestible nutrients was computed by adding the digestibility of all organic compounds, and acceptance of the food was made through offering it as a first option to the sows from two farms. The organic solid residues of craft beer contain an average 2.43% of ash, 1.99% of ethereal extract, 4.91% of crude fiber, 64.20% of nitrogen-free extract, 10.91% of crude protein, and 73.47% of total digestible nutrients. The food achieved an acceptance of 83.4% when it was offered alone and 100% combined with other ingredients.RESUMEN Se realizó un análisis químico proximal en residuos sólidos orgánicos de tres tipos de cerveza artesanal y detecto su aceptación en la alimentación de cerdas. Para determinar humedad de residuos de cerveza se utilizó estufa a 105°C durante 24 horas, el extracto etéreo se determinó con equipo Soxhlet y éter etílico como solvente, la determinación de cenizas se realizó por calcinación en mufla a 700°C, para fibra cruda se utilizó digestión ácida con ácido sulfúrico 0.2 N, para proteína cruda se empleó equipo Kjedahl, el extracto libre de nitrógeno se determinó por diferencia del 100% de la suma de humedad, cenizas, grasa, proteína y fibra. El total de nutrientes digeribles se realizó mediante la sumatoria de la digestibilidad de los compuestos orgánicos. Los residuos sólidos orgánicos de cerveza artesanal contienen en promedio 2.43% de cenizas, 1.99% de extracto etéreo, 4.91% de fibra cruda, 64.20% de extracto libre de nitrógeno, 10.91% de proteína cruda y 73.47% de nutrientes digestibles totales. La determinación de la aceptación del alimento se realizó ofreciéndolo como primera opción a las cerdas de dos granjas. El alimento tuvo una aceptación de 83.4% cuando se ofreció solo y del 100% combinado con otros ingredientes

Microorganismos de montaña y ensilado de maíz como probióticos en la engorda de conejos

There are bacteria that produce lactic acid (LAB) present in the epiphytic microflora of plants, and consortia of mountain microorganisms such as yeasts and mixed cultures that can be used as probiotics and growth promoters in animal production. To evaluate the use of mountain microorganisms in corn silage as probiotics in the fattening of rabbits for 4 weeks, 20 hybrid rabbits were used. Which were chosen randomly in each treatment. The preparation of the probiotics was carried out through an initial anaerobic fermentation stage and a final aerobic one. Treatment (T1) was a diet supplemented with the addition of mountain microorganisms in corn silage (MME) in the drinking water and treatment two or conventional (T2) served as a control without application of MME. The feed consumption and the feed conversion index were calculated, expressed as the mean ± the standard deviation. When performing an analysis of variance (ANOVA), it was established that during week 4 of treatment there was a significant difference (P <0.05) in weight gain and feed conversion between treatments, being favorable for T1 supplemented with MME.Existen bacterias que producen ácido láctico (BAL) presentes en la microflora epifita de los vegetales, y consorcios de microorganismos de montaña como levaduras y cultivos mixtos que pueden ser empleados como probióticos y promotores del crecimiento en la producción animal.Para evaluar el uso de microorganismos de montaña en ensilado de maíz como probióticos en la engorda de conejos durante 4 semanas, se emplearon 20 conejos híbridos. Los cuales se escogieron aleatoriamente en cada tratamiento. La preparación de los probióticos se realizó mediante una etapa de fermentación inicial anaerobia y una final aerobia. El tratamiento (T1) fue una dieta suplementada con la adición de microorganismos de montaña en ensilado de maíz (MME) en el agua de bebida y el tratamiento dos o convencional (T2) fungió como testigo sin aplicación de MME. Se calculó el consumo de alimento y el indicie de conversión alimenticia, expresados como la media ± la desviación estándar. Al realizar un análisis de varianza (ANOVA) se estableció que durante la semana 4 del tratamiento hubo diferencia significativa (P<0.05) en la ganancia de peso y conversión alimenticia entre los tratamientos, siendo favorable para T1 suplementados con MM

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (&lt;45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale &amp; Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting &amp; Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (&lt;60, 60-69, and &gt;_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 &amp; PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages &lt;60, 60-69, and &gt;_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791