Antitussive and toxicological evaluation of Vitex negundo

Vitex negundo Linn. (Verbenaceae) is used in traditional medical system for respiratory disorders. This study was carried out to investigate its cough-relieving potential. The antitussive effect of the butanolic extract of V. negundo (Vn) on sulphur dioxide (SO(2))-induced cough was examined in mice. Safety profile of Vn was carried out by observing acute neurotoxicity, median lethal dose (LD(50)) and behavioural signs. Vn dose-dependently (250-1000?mg?kg(-1)) inhibited the cough provoked by SO(2) gas in mice and exhibited maximum protection after 60?min of administration. At 1000?mg?kg(-1), Vn caused maximum cough-suppressive effects i.e. cough inhibition at 60?min was 67.4%, as compared to codeine (10?mg?kg(-1)), dextromethorphan (10?mg?kg(-1)) and saline having cough-inhibitory potential 75.7%, 74.7% and 0%, respectively. LD(50) value of V. negundo was found to be greater than 5000?mg?kg(-1). In toxicity tests, no signs of neural impairment and acute behavioural toxicity were observed at antitussive doses and extract has been well tolerated at higher doses. These results indicate that V. negundo exhibits antitussive effect and it was found devoid of toxicity.     

Determination of perfluoroalkyl carboxylic, sulfonic, and phosphonic acids in food

A sensitive and accurate method was developed and validated for simultaneous analysis of perfluoroalkyl carboxylic acids, sulfonic acids, and phosphonic acids (PFPAs) at low picograms per gram concentrations in a variety of food matrices. The method employed extraction with acetonitrile/water and cleanup on a mixed-mode co-polymeric sorbent (C8?+?quaternary amine) using solid-phase extraction. High-performance liquid chromatographic separation was achieved on a C18 column using a mobile phase gradient containing 5?mM 1-methyl piperidine for optimal chromatographic resolution of PFPAs. A quadrupole time-of-flight high-resolution mass spectrometer operating in negative ion mode was used as detector. Method detection limits were in the range of 0.002 to 0.02?ng?g^?1 for all analytes. Sample preparation (extraction and cleanup) recoveries at a spiking level of 0.1?ng?g^?1 to a baby food composite were in the range of 59 to 98?%. A strong matrix effect was observed in the analysis of PFPAs in food extracts, which was tentatively assigned to sorption of PFPAs to the injection vial in the solvent-based calibration standard. The method was successfully applied to a range of different food matrices including duplicate diet samples, vegetables, meat, and fish samples.

Stability indicating HPLC method for the simultaneous determination of moxifloxacin and prednisolone in pharmaceutical formulations

ABSTRACT: BACKGROUND: A simple, specific, and fast stability indicating reverse phase liquid chromatographic method was established for instantaneous determination of moxifloxacin and prednisolone in bulk drugs and pharmaceutical formulations. RESULTS: Optimum chromatographic separations among the moxifloxacin, prednisolone and stressinduced degradation products were achieved within 10 minutes by use of BDS Hypersil C8 column (250 X 4.6 mm, 5 mum) as stationary phase with mobile phase consisted of a mixture of phosphate buffer (18 mM) containing 0.1% (v/v) triethylamine, at pH 2.8 (adjusted with dilute phosphoric acid) and methanol (38:62 v/v) at a flow rate of 1.5 mL min-1. Detection was performed at 254 nm using diode array detector. The method was validated in accordance with ICH guidelines. Response was a linear function of concentrations over the range of 20-80 mug mL-1 for moxifloxacin (r2 [greater than or equal to] 0.998) and 40-160 mug mL-1 for prednisolone (r2 [greater than or equal to] 0.998). The method was resulted in good separation of both the analytes and degradation products with acceptable tailing and resolution. The peak purity index for both the analytes after all types of stress conditions was [greater than or equal to] 0.9999 indicated a complete separation of both the analyte peaks from degradation products. The method can therefore, be regarded as stabilityindicating. CONCLUSIONS: The developed method can be applied successfully for simultaneous determination of moxifloxacin and prednisolone in pharmaceutical formulations and their stability studies.     

Handling equality constraints in evolutionary optimization

Over the last few decades several methods have been proposed for handling functional constraints while solving optimization problems using evolutionary algorithms (EAs). However, the presence of equality constraints makes the feasible space very small compared to the entire search space. As a consequence, the handling of equality constraints has long been a difficult issue for evolutionary optimization methods. This paper presents a Hybrid Evolutionary Algorithm (HEA) for solving optimization problems with both equality and inequality constraints. In HEA, we propose a new local search technique with special emphasis on equality constraints. The basic concept of the new technique is to reach a point on the equality constraint from the current position of an individual solution, and then explore on the constraint landscape. We believe this new concept will influence the future research direction for constrained optimization using population based algorithms. The proposed algorithm is tested on a set of standard benchmark problems. The results show that the proposed technique works very well on those benchmark problems.     

Prospect of Anterior Gradient 2 homodimer inhibition via repurposing FDA-approved drugs using structure-based virtual screening

Anterior Gradient 2 (AGR2) has recently been reported as a tumor biomarker in various cancers, i.e., breast, prostate and lung cancer. Predominantly, AGR2 exists as a homodimer via a dimerization domain (E60-K64); after it is self-dimerized, it helps FGF2 and VEGF to homo-dimerize and promotes the angiogenesis and the invasion of vascular endothelial cells and fibroblasts. Up till now, no small molecule has been discovered to inhibit the AGR2–AGR2 homodimer. Therefore, the present study was performed to prepare a validated 3D structure of AGR2 by homology modeling and discover a small molecule by screening the FDA-approved drugs library on AGR2 homodimer as a target protein. Thirteen different homology models of AGR2 were generated based on different templates which were narrowed down to 5 quality models sorted by their overall Z-scores. The top homology model based on PDB ID?=?3PH9 was selected having the best Z-score and was further assessed by Verify-3D, ERRAT and RAMPAGE analysis. Structure-based virtual screening narrowed down the large library of FDA-approved drugs to ten potential AGR2–AGR2 homodimer inhibitors having FRED score lower than ? 7.8 kcal/mol in which the top 5 drugs’ binding stability was counter-validated by molecular dynamic simulation. To sum up, the present study prepared a validated 3D structure of AGR2 and, for the first time reported the discovery of 5 FDA-approved drugs to inhibit AGR2–AGR2 homodimer by using structure-based virtual screening. Moreover, the binding of the top 5 hits with AGR2 was also validated by molecular dynamic simulation.

Graphic abstract

A validated 3D structure of Anterior Gradient 2 (AGR2) was prepared by homology modeling, which was used in virtual screening of FDA-approved drugs library for the discovery of prospective inhibitors of AGR2–AGR2 homodimer.

     

Heat pipes: progress in thermal performance enhancement for microelectronics

Journal of Thermal Analysis and Calorimetry - The aim of this study is to oversee the impact of various techniques on thermal performance of heat pipes and to comprehensively cover the progress...     

Single nucleon distribution based on shell-model and matrix ensemble theory

An expression for the density of single nucleons in a heavy spherical nucleus is derived using the shell-model and matrix ensembles. It is shown that the theoretical expression gives an excellent fit to the density of nucleons for the nucleus¹⁹⁷Au obtained usinge-scattering data.     

Exact generator coordinate wave functions for some simple hamiltonians

We obtain the superconformal transformation laws of theN=4 supersymmetric Yang-Mills theory and explicitly demonstrate the closure of the algebra.     

Synthesis,characterization and biological analysis of transition metal complexes with macro cyclic ligands derived from adipic acid,ethylenediamine with diethyloxalate and diethylmalonate

Macro-cyclic ligands from adipic acid, ethylenediamine with diethyloxalate and diethylmalonate and their respective metal complexes of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) with macro cyclic ligands (LO) and (LM) L [N,N′-bis(2-aminoethyl)hexanediamide] were synthesized successfully. These metal complexes were characterized by Fourier transform infrared, ultraviolet visible spectrometry, proton nuclear magnetic resonance spectroscopy, and mass Spectrometry, CHNS and thermogravimetric analysis. The elemental analysis confirms the structures for Mn(II), Co(II) and Ni(II) complexes similar to octahedral geometry, Cu(II) complexes as a square planar geometry and Zn(II) complexes in the tetrahedral geometry. The molar conductivities of all the metal complexes were taken in 10^?3 M DMSO, and values of all the metal complexes showed their electrolytic nature which indicates the presence of chloride ions. Thermal analysis supports as the metal complexes are thermally stable. The result of antimicrobial activity against various microorganisms confirms that the metal complexes are potent bactericides and fungicides than the ligand. Metal complexes of LO with Cu(II) and Zn(II) were found to be highly active against S. typhimurium than the complexes of LM.

Graphical abstract

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