Efficacy and safety of fixed-dose combination of Bilastine-Montelukast in adult patients with allergic rhinitis: a phase III, randomized, multi-center, double-blind, active controlled clinical study.

BACKGROUND: Histamine and cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators in allergic rhinitis (AR). Studies involving other combinations of antihistaminics (Levocetirizine) and highly selective leukotriene receptor antagonist (LTA) (Montelukast) combination have shown additive benefits and are widely prescribed for AR. OBJECTIVE: Evaluate the efficacy and safety of Bilastine 20 mg and Montelukast 10 mg fixed-dose combination (FDC) therapy in patients with AR. METHODS: A randomized, double-blind, comparative, parallel, phase III study was conducted to evaluate efficacy and safety of Bilastine 20 mg and Montelukast 10 mg FDC at 16 tertiary care otolaryngology centres in India. Adult patients with AR for one year with IgE antibody positive and 12-h NSS score >36 in 3 days were randomized to receive either Bilastine 20 mg and Montelukast 10 mg or Montelukast 10 mg & Levocetirizine 5 mg tablets for 4 weeks. The change in total symptom score (nasal symptom scores (NSS) & non-nasal symptom scores (NNSS)) from baseline to week 4 was assessed as primary endpoint. Secondary endpoints included changes in TSS, NSS, NNSS, individual symptom scores (ISS), Rhinoconjunctivitis Quality of Life (RQLQ), discomfort due to rhinitis (VAS), and clinical global impression (CGI) scores. RESULTS: The change in mean TSS from baseline to week 4 in Test group (16.6 units) was comparable to reference group (17 units) (p= 0.8876). The difference in change in mean NSS, NNSS and ISS from baseline to day 7, 14, 28 were comparable. RQLQ improved from baseline to Day 28. Significant improvements were observed in discomfort due to AR measured by VAS and CGI scores from baseline to day 14 and 28. The safety and tolerability of patients were comparable between the groups. All adverse events (AEs) were mild to moderate in severity. No patient discontinued due to AEs. CONCLUSIONS: The FDC of Bilastine 20 mg and Montelukast 10 mg was efficacious and well tolerated in Indian patients with AR.

Anticancer effect and apoptosis induction by azaflavanone derivative in human prostate cancer cells.

Polyphenols are naturally occurring organic compounds with varying structures represented by four major groups: flavonoids, phenolic acids, lignans and stilbenes. Several studies suggested that these secondary metabolites have health benefits due to its anti-tumorigenic effect. Therefore, substantial effort has been put forward to isolate and characterize these natural compounds and synthesize analogues that may serve as potential anti-cancer therapeutics. This present study is aimed at designing and synthesis of azaflavanone derivative and in understanding its mechanism of action in vitro and in vivo. Molecular docking studies predicted that the compound can potentially bind strongly to the Cyclin E1-Cdk2 complex which is a key mediator of the cell cycle progression indicating a biological interference in aggressive prostate cancer. Further downstream studies to understand its cytotoxicity and mechanism of action showed this azaflavanone derivative markedly inhibits viability of prostate cancer cells (DU145) showing an IC50 value of 0.4 µM compared to other cancer cells. The pharmacological ROS insult using the azaflavanone derivative increases the oxidative damage leading to high expression of apoptotic markers with increasing concentration. On compound treatment, the cells lose the metabolic flexibility accompanied by mitochondrial dysfunction leading to cell cycle arrest and apoptosis. Further, no compound mediated toxicity was observed in xenograft mouse model of prostate cancer at a concentration as high as 5 mg/kg. The tumor burden was reduced to 60% rendering the azaflavanone derivative a potential candidate in cancer therapeutics. Collectively, the compound triggers cell cycle arrest and ROS mediated oxidative stress sensitizing the cancerous cells towards apoptosis.

Biosynthesis of CMC-Guar gum-Ag0 nanocomposites for inactivation of food pathogenic microbes and its effect on the shelf life of strawberries.

A few fruits have short post-harvest life due to high metabolic activity, relatively high water content vulnerability towards microbes and loss of weight during their storage. Carboxymethyl cellulose (CMC)-Guar gum-silver nanocomposite films (CG-Ag0NC) are developed to address these issues. The silver nanoparticles were generated in the CMC-Guar gum matrix through a reduction by Mentha leaves extract. All the films were characterized by UV-vis spectroscopy, FT-IR, TGA, XRD, SEM, TEM, and zeta potential measurements. The antimicrobial activity of CG and CG-Ag0NC was measured by determining their zone inhibition values with ten food pathogenic microbes. The shelf life of CG-Ag0NC films was tested with the model fruit, strawberries, and compared with other packing films. The results are encouraging in terms of freshness, shelf-life and weight loss.

Radioactivity levels in the atomic mineral occurrences along Dharmapuri Shear zone in parts of Vellore, Krishnagiri, Dharmapuri and Salem districts of Tamil Nadu, India.

The aim of this study was to evaluate the concentrations of naturally occurring radioactive nuclides 226Ra, 232Th and 40K and corresponding dose rates over atomic mineral occurrences of Dharmapuri shear zone in parts of Salem, Dharmapuri, Krishnagiri, and Vellore districts of Tamilnadu, India. In this paper, area-wise ternary diagrams of Ra, Th and K were plotted to study their relative concentration in the samples. Correlation study was also carried out to delineate the contribution of individual radionuclides toward the measured gamma dose rate. The concentrations of Ra, Th and K were determined by gamma ray spectrometry system using a 5" × 4" NaI (Tl) detector assembly. The geometric mean values of the estimated annual effective outdoor dose equivalent (AEDE) in mSv/y in the four areas were 2.35, 0.72, 1.88 and 0.36. A good linear correlation was observed between the estimated and measured annual effective dose equivalent.

A novel domino cyclization for the stereoselective synthesis of indeno[2,1-c]pyran and cyclopenta[c]pyran derivatives.

A novel bicyclization of 2-(2-(hydroxymethyl)-1-methylene-2,3-dihydro-1H-inden-2-yl)ethanol with aldehydes in the presence of 10 mol% BF3·OEt2 in dichloromethane at 0-25 °C affords the biologically relevant indeno[2,1-c]pyran scaffolds in good yields with high selectivity. Similarly the bicyclization of 2-(1-(hydroxymethyl)-2-methylenecyclopentyl)ethanol with aldehydes generates the corresponding cyclopenta[c]pyran derivatives under similar conditions. This method is very useful to produce hematoxylin and brazilin like scaffolds.