Association between uric acid levels and cardio-renal outcomes and death in patients with type 2 diabetes: A subanalysis of EMPA-REG OUTCOME

In the EMPA-REG OUTCOME trial, we explored the association between pre-randomization uric acid level tertile (<309.30 μmol/L; 309.30 to <387.21 μmol/L; ≥387.21 μmol/L) and cardiovascular (CV) death, hospitalization for heart failure (HHF), HHF or CV death, all-cause mortality, three-point major adverse CV events (MACE), and incident or worsening nephropathy. Patients with type 2 diabetes and CV disease received empagliflozin or placebo. The median baseline plasma uric acid level was 344.98 μmol/L, and patients’ baseline characteristics were mainly balanced across tertiles. Baseline uric acid levels were associated with cardio-renal outcomes: in the placebo group, for the highest versus lowest tertile, the multivariable hazard ratios for three-point MACE, HHF or CV death, and incident or worsening nephropathy were 1.22 (95% confidence interval [CI] 0.89–1.67; P = 0.2088), 1.51 (95% CI 1.02–2.23; P = 0.0396) and 1.77 (95% CI 1.33–2.34; P < 0.0001), respectively. When tested as a continuous variable, baseline uric acid was associated with all outcomes in the placebo group. Empagliflozin improved all cardio-renal outcomes across tertiles, with all interaction P values >0.05. Further investigation of these relationships is required.     

Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4‐week,double‐blind,randomized, placebo‐controlled phase 2 trial

Aims

This phase 2, double‐blind, randomized, placebo‐controlled trial ( ClinicalTrials.gov NCT02702011) with 4 sites in Japan investigated the pharmacodynamics (PD), pharmacokinetics (PK) and safety profile of empagliflozin in Japanese participants with type 1 diabetes mellitus (T1DM) as adjunctive therapy to insulin.

Materials and methods

Participants using multiple daily injections of insulin for ≥12 months, with HbA1c of 7.5%‐10.0%, entered a 2‐week, open‐label, placebo run‐in period, followed by a 4‐week, double‐blind period during which participants were randomized 1:1:1:1 to receive empagliflozin 2.5 mg (n = 13), empagliflozin 10 mg (n = 12), empagliflozin 25 mg (n = 12) or placebo (n = 11). The primary objective was to assess the effect of empagliflozin vs placebo on urinary glucose excretion (UGE) after 7 days of treatment.

Results

PD: Empagliflozin resulted in a dose‐dependent significant increase in 24‐hour UGE compared with placebo (UGE placebo‐corrected mean [95% confidence interval] change from baseline: 2.5 mg, 65.10 [43.29, 86.90] g/24 h; 10 mg, 81.19 [58.80, 103.58] g/24 h; 25 mg, 98.11 [75.91, 120.31] g/24 h). After 4 weeks of treatment, UGE increase was associated with improved glycaemic control, reduced body weight and decreased insulin needs. Empagliflozin treatment also resulted in dose‐dependent increases in serum ketone bodies and free fatty acids. PK: Plasma empagliflozin levels increased in a dose‐dependent manner and peaked at 1.5 hours. In this short study, empagliflozin was well tolerated, with no increase in rate of hypoglycaemia and no diabetic ketoacidosis events reported.

Conclusions

Based on this short‐duration phase 2 study, the PK/PD profile of empagliflozin in Japanese participants with T1DM is comparable to that of non‐Japanese participants.     

Valencene-rich fraction from Vetiveria zizanioides exerts immunostimulatory effects in vitro and in mice

Objective: To decipher the responsible compound present in the aqueous root extract of Vetiveria zizanioides which has tremendous immunomodulatory activity. Met...     

Studies on biofilm formation and virulence factors associated with uropathogenic Escherichia coli isolated from patient with acute pyelonephritis

The current study aims to the detection of pathogenic potential and virulence factor identification of uropathogenic Escherichia coli BRL-17 isolated from patients urine. The organism was isolated from the patient with chronic pyelonephritis. The identification of organism was done by analyzing gram staining, biochemical, 16S rDNA analysis, Raman microscopy and SEM analysis. The pathogenic potential was identified by multiplex PCR analysis of virulence factor genes like sfa, hly D, pap C. The biofilm forming ability was tested by congo red agar assay and tissue culture plate assay. The result of gram staining and biochemical analysis shows the characteristics of E-coli. The 16S rDNA analysis of the clinically isolated uropathogen showed 100% similarity with uropathogenic Escherichia coli strain. Raman microscopy and SEM confirms the organism as E-coli. The Multiplex PCR study identifies virulence genes like sfa, hly D, pap C in isolated E-coli. The presence of P fimbriae coded pap C gene, S fimbriae coded sfa gene and hemolysin-D coded hly D gene discloses its potential to cause urinary tract infection. Biofilm assay result enhances the organism’s role as strong biofilm former. This biofilm forming ability of Escherichia coli strain BRL-17 made the organism to escape from host immune system and helps to colonize in bladder and kidney. This also helps to enhance the resistance to antibiotics. Our study confirms the organism as multidrug resistant, highly virulent, strong biofilm forming E-coli. The strain may be used for the development of animal models of pyelonephritis for the purpose of drug discovery.     

Plant Growth Promoting Endophytic Serratia sp. ZoB14 Protecting Ginger from Fungal Pathogens

Soft rot caused by Pythium sp. is a major challenge to the cultivation of Zingiber officinale Rosc. (Ginger). In the present study, endophytic Serratia sp. ZoB14 isolated from ginger rhizome was found to have inhibitory effect towards Pythium myriotylum and also against other pathogens. This was confirmed by dual culture and scanning electron microscopic analysis. Further, ZoB14 was identified to have the presence of aminopyrrolnitrin oxidase gene involved in the biosynthesis of pyrrolnitrin. The rhizome bacterization with ZoB14 has revealed its protective effect to ginger from Pythium infection. In addition, the organism was observed to have the presence of an array of plant growth promoting traits with in vivo growth enhancement effect on Vigna unguiculata seedlings. Even though Serratia species have previously been reported for antifungal properties, its plant growth supportive features and isolation from rhizome of ginger make the study highly significant.