Response of Asthmatics to Isoprenaline and Salbutamol Aerosols Administered by Intermittent Positive-pressure Ventilation

The bronchodilator and cardiac effects produced by aerosols of 0·5% isoprenaline and of 0·25, 0·5, and 1% salbutamol administered in 40% oxygen by intermittent positive-pressure ventilation were compared in 24 asthmatic patients. Isoprenaline and salbutamol in concentrations of 0·5% were equipotent in peak bronchodilator effect; salbutamol was superior in total bronchodilator effect and duration of average effect, but the peak bronchodilator effect occurred earlier after isoprenaline. Significantly greater tachycardia was produced by 0·5% isoprenaline than by the same concentration of salbutamol. The 0·25, 0·5, and 1% concentrations of salbutamol had about the same peak bronchodilator effect, but there was a stepwise increase in total effect and duration of average effect in relation to the concentration used. A similar stepwise increase in heart rate was also noted, but with all concentrations this was significantly less than with 0·5% isoprenaline. It was concluded that a 0·5% solution of salbutamol, which provided maximal bronchodilatation without important tachycardia, was therapeutically superior to the other three treatments.     

Adsorption of adipic acid in Al/B-N/P nanocages: DFT investigations

The biomolecular recognition of D-mannose-binding lectin from Artocarpus heterophyllus (ArtinM) by Horseradish Peroxidase (HRP) mediated by glycosylation allows their application in a multitude of biological systems. The present work describes the use of molecular dynamics (MD) to assess the Gibbs free energy associated with the formation of a ArtinM-HRP conjugate mediated by a glycosylation molecule. For the enthalpy term, we applied the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method and for the vibrational entropy term, we use the quasi-harmonic approximation. Our results show that, even without glycosylation, the binding free energy between ArtinM and HRP is − 196.154 kJmol^− 1, an extremely high affinity with low selectivity, originated mainly through the van der Waals energy terms. The binding free energy between ArtinM and the glycosylated HRP (gHRP) was calculated at − 66.156 kJmol^− 1, an absolute and considerably lower value, however, originated from electrostatic energy terms, which increases the selectivity of molecular recognition. Our work has shown that the HRP active site region has a high affinity and low selectivity for other biomolecules. The presence of glycosylation plays a role in increasing this selectivity for this region. Thus, we conclude that performing mutagenesis of amino acid residues near the entrance of the catalytic site, can improve the activity of non-glycosylated HRPs. This illustrates new insights that can be applied to carbohydrate-based immunochemistry.

     

Green synthesis and characterization of zinc oxide nanoparticles using Cayratia pedata leaf extract

The synthesis of Zinc oxide nanoparticles using a plant-mediated approach is presented in this paper. The nanoparticles were successfully synthesized using the Nitrate derivative of Zinc and plant extract of the indigenous medicinal plant Cayratia pedata. 0.1 mM of Zn (NO₃)₂.6H₂O was made to react with the plant extract at different concentrations, and the reaction temperature was maintained at 55 °C, 65 °C, and 75 °C. The yellow coloured paste obtained was wholly dried, collected, and packed for further analysis. In the UV visible spectrometer (UV–Vis) absorption peak was observed at 320 nm, which is specific for Zinc oxide nanoparticles. The characterization carried out using Field Emission Scanning Electron Microscope (FESEM) reveals the presence of Zinc oxide nanoparticles in its agglomerated form. From the X-ray diffraction (XRD) pattern, the average size of the nanoparticles was estimated to be 52.24 nm. Energy Dispersive Spectrum (EDX) results show the composition of Zinc and Oxygen, giving strong energy signals of 78.32% and 12.78% for Zinc and Oxygen, respectively. Fourier Transform - Infra-Red (FT-IR) spectroscopic analysis shows absorption peak of Zn–O bonding between 400 and 600 cm^?1. The various characterization methods carried out confirm the formation of nano Zinc oxide. The synthesized nanoparticles were used in the immobilization of the enzyme Glucose oxidase. Relative activity of 60% was obtained when Glucose oxidase was immobilized with the green synthesized ZnO nanoparticles. A comparative study of the green synthesized with native ZnO was also carried out. This green method of synthesis was found to be cost-effective and eco-friendly.     

Therapeutic efficacy of anti‐MMP9 antibody in combination with nab‐paclitaxel‐based chemotherapy in pre‐clinical models of pancreatic cancer

Matrix metalloproteinase 9 (MMP9) is involved in the proteolysis of extracellular proteins and plays a critical role in pancreatic ductal adenocarcinoma (PDAC) progression, invasion and metastasis. The therapeutic potential of an anti‐MMP9 antibody (αMMP9) was evaluated in combination with nab‐paclitaxel (NPT)‐based standard cytotoxic therapy in pre‐clinical models of PDAC. Tumour progression and survival studies were performed in NOD/SCID mice. The mechanistic evaluation involved RNA‐Seq, Luminex, IHC and Immunoblot analyses of tumour samples. Median animal survival compared to controls was significantly increased after 2‐week therapy with NPT (59%), Gem (29%) and NPT+Gem (76%). Addition of αMMP9 antibody exhibited further extension in survival: NPT+αMMP9 (76%), Gem+αMMP9 (47%) and NPT+Gem+αMMP9 (94%). Six‐week maintenance therapy revealed that median animal survival was significantly increased after NPT+Gem (186%) and further improved by the addition of αMMP9 antibody (218%). Qualitative assessment of mice exhibited that αMMP9 therapy led to a reduction in jaundice, bloody ascites and metastatic burden. Anti‐MMP9 antibody increased the levels of tumour‐associated IL‐28 (1.5‐fold) and decreased stromal markers (collagen I, αSMA) and the EMT marker vimentin. Subcutaneous tumours revealed low but detectable levels of MMP9 in all therapy groups but no difference in MMP9 expression. Anti‐MMP9 antibody monotherapy resulted in more gene expression changes in the mouse stroma compared to the human tumour compartment. These findings suggest that anti‐MMP9 antibody can exert specific stroma‐directed effects that could be exploited in combination with currently used cytotoxics to improve clinical PDAC therapy.     

Lectin Histochemistry of Normal Human Lung

This study aimed to identify and specify the glycotypes of cell populations in normal human lung including types I and II pneumocytes, alveolar macrophages and mast cells, and also in the larger tissue structures of lung, including blood vessels and bronchi/bronchioles, using lectin- and immuno-histochemistry on paraffin-embedded tissue from 11 normal cases. The alveolar macrophages were anti-CD68 positive whereas the cells lining the alveolar walls were positive for cytokeratins. The alveolar macrophages in normal lung tissues showed a broad spectrum of staining for different subsets of N-linked saccharides, N-acetylgalactosamine, N-acetylglucosamine, terminal beta-D-galactose and sialyl groups. This study showed that some lectins could be used as specific markers for some cell types i.e. Galanthus nivalis and Narcissus pseudonarcissus lectins for macrophages, Psophocarpus tetragonolobus lectin-II for capillary endothelium, Dolichos biflorus agglutinin for bronchial epithelial cells, Lycopersicon esculentum, Phytolacca americana or Triticum vulgaris (succinylated) for type I pneumocytes and Hippeastrum hybrid or Maclura pomifera lectins for type II pneumocytes. Patchy staining of type I pneumocytes by peanut agglutinin indicated the possibility of two distinct populations of these cells or a pattern of differentiation that is unapparent morphologically.