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

Green synthesis of palladium nanoparticles using gum ghatti (Anogeissus latifolia) and its application as an antioxidant and catalyst

A facile and green route for the synthesis of palladium nanoparticles from palladium chloride was developed using non-toxic, renewable plant polymer, gum ghatti (Anogeissus latifolia), as both the reducing and stabilizing agent. The generated nanoparticles were characterized with UV–visible spectroscopy (UV–vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), and X-ray diffraction (XRD) techniques. The formation of palladium nanoparticles was confirmed from the appearance of intense brown colour and broad continuous absorption spectra in the UV–visible region. The produced nanoparticles were found to be spherical in shape, polydisperse and the average particle size was 4.8 ± 1.6 nm. The face centred cubic crystal structure of the fabricated nanoparticles is confirmed from the selected-area electron diffraction and XRD patterns. Compared to earlier reports, the nanoparticles showed superior antioxidant at a much lower nanoparticle dose. Also, the homogenous catalytic activity of palladium nanoparticles was studied by probing the reduction of dyes such as coomassie brilliant blue G-250, methylene blue, methyl orange, and a nitro compound, 4-nitrophenol with sodium borohydride. The nanoparticles exhibited excellent catalytic activity in dye degradation and the results of this study demonstrate the possible application of biogenic palladium nanoparticles as nanocatalyst in environmental remediation. Keywords: Antioxidant, Catalyst, Green synthesis, Gum ghatti, Palladium nanoparticles, Dye degradatio

Enhancement of Antibacterial Activity of Capped Silver Nanoparticles in Combination with Antibiotics, on Model Gram-Negative and Gram-Positive Bacteria

The nanoparticles used in this study were prepared from AgNO3 using NaBH4 in the presence of capping agents such as citrate, sodium dodecyl sulfate, and polyvinylpyrrolidone. The formed nanoparticles were characterized with UV-Vis, TEM, and XRD. The generation of silver nanoparticles was confirmed from the appearance of yellow colour and an absorption maximum between 399 and 404 nm. The produced nanoparticles were found to be spherical in shape and polydisperse. For citrate, SDS, and PVP capped nanoparticles, the average particle sizes were 38.3±13.5, 19.3±6.0, and 16.0±4.8 nm, respectively. The crystallinity of the nanoparticles in FCC structure is confirmed from the SAED and XRD patterns. Also, the combined antibacterial activity of these differently capped nanoparticles with selected antibiotics (streptomycin, ampicillin, and tetracycline) was evaluated on model Gram-negative and Gram-positive bacteria, employing disc diffusion assay. The activity of the tested antibiotics was enhanced in combination with all the stabilized nanoparticles, against both the Gram classes of bacteria. The combined effects of silver nanoparticles and antibiotics were more prominent with PVP capped nanoparticles as compared to citrate and SDS capped ones. The results of this study demonstrate potential therapeutic applications of silver nanoparticles in combination with antibiotics

Development of microwave assisted-UV digestion using diluted reagents for the determination of total nitrogen in cereals by ion chromatography

The objective of this work is to develop a microwave assisted-ultraviolet (MW-UV) digestion in the presence of dilute HCl and H2O2 followed by ion chromatography (IC) measurements for the determination of total nitrogen in cereals. This approach (MW-UV-IC) requires lesser time and does not need environmentally hazardous materials as used in Kjeldhal method. Further, the developed method requires only microliter quantities of dilute HCl and few milliliters of H2O2 for the matrix digestion and simultaneous conversion of nitrogen to its ionic species for the subsequent analysis by IC. At the optimized acid concentrations (200 ​μL of 0.1 ​mol ​L−1 HCl) and microwave power, the nitrogen in the cereals flours is converted to nitrate (NO3−), nitrite (NO2−) and ammonium (NH4+) ions. The nitrogen species were separated using IonPac AS-20 and IonPac CS-17 columns and then quantified using suppressed conductivity detection. The method was applied to estimate the total nitrogen in flours of various cereals like; wheat (Triticum aestivum), rice (Oryza sativa), finger millet (Eleusine coracana), jowar (Sorghum) and pearl millet (Pennisetum glaucum). The results obtained using proposed method, were in good agreement with that of Kjeldhal method. Further, the precision of the values obtained by developed method was on par with the Kjeldhal method for all the tested flours as verified by F-test (n ​= ​5 and 95% confidence limit). Additionally, greenness assessment tools like analytical Eco-scale and green analytical procedure index (GAPI) suggested the proposed MW-UV-IC method, for the determination of total nitrogen in cereal flours, to be excellently green and safe

ArsenazoIII functionalized gold nanoparticles: SPR based optical sensor for determination of uranyl ions (UO22+) in groundwater

Surface plasmon resonance (SPR) based spectrophotometric determination of UO22+ was carried out by arsenazoIII functionalized gold nanoparticles (AZ-AuNPs) based miniaturized detection assay in ground water samples. AZ-AuNPs were synthesized, characterized by transmission electron microscopy (TEM), x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS), infrared spectroscopy (IR) and dynamic light scattering (DLS) techniques; AZ-AuNPs were of uniform size (∼10nm), dispersed, highly stable and negative charge surface. The addition of analyte (UO22+) into the detection assay led to UO22+-arsenazoIII complex formation and subsequent release of uncapped gold nanoparticules in solution. Agglomeration based SPR response of gold nanoparticles resulted in visual and spectrophotometric change in the detection assay. The UV-vis spectroscopic investigations showed changes in AZ-AuNPs characteristic absorption peak and an additional peak correspond to UO22+-arsenazoIII complex. Ratio of A650nm/A535nm was used to quantify the concentration of UO22+ in environmental samples. The method showed a linear response from 50−300 ppb (R2> 0.95) for UO22+ with the detection limit of 0.081 µM for ground water samples of total dissolve solids concentration of ∼1000 ppm

Physico-chemical and bacteriological screening of Hussain Sagar lake: An urban wetland

Hussain Sagar is a man-made lake originally designed for drinking water purpose that receives domestic sewage and industrial effluents through drainage canals due to rapid residential and industrial growth. Also, every year thousands of idols are immersed into the lake during festivals. In this context, a comprehensive study was initiated for monitoring the lake water quality. Various physico-chemical parameters such as temperature, pH, EC, TDS, COD and chlorophyll a were analyzed using APHA standard methods Water was also monitored for heterotrophic bacteria, total coliforms, Escherichia coli and antibiotic resistant bacteria. The average values for heterotrophs were found to be 8.6 × 104 and 2.8 × 104 CFU/mL before and after idol immersion, respectively. While the average values for total coliforms and E. coli were 5 × 104 and 5 × 102; 1.2 × 104 and 7.2 × 101 CFU/mL, for the respective sampling periods. The mean values for ampicillin and gentamicin resistant bacteria were 5.9 × 103 and 6.9 × 102; and 2.2 × 103 and 5.4 × 102 CFU/mL, respectively. It was found that TDS, COD and chlorophyll a values were decreased after idol immersion due to extensive cleaning. The statistical results showed no correlation between faecal bacteria and physico-chemical parameters and one way-ANOVA indicated statistically significant differences between the mean values of different sampling locations, with respect to COD and E. coli at 95% confidence. However, enormous load of coliforms and E. coli indicated severe contamination of the lake with domestic sewage and human excreta. Thus, the water is not suitable for human consumption/drinking purpose. Notably, incidence of antibiotic resistant bacteria in lake water is a potential threat to both public health and the environment. Thus, regular monitoring and applying appropriate corrective actions are needed to improve the water quality