Topical Astodrimer Sodium,a Non-Toxic Polyanionic Dendrimer,Demonstrates Antiviral Activity in an Experimental Ocular Adenovirus Infection Model

There is no approved antiviral therapy for adenovirus (HAdV) ocular infections. Astodrimer sodium (SPL7013) is a polyanionic dendrimer with antiviral activity. The current study evaluated the ocular tolerability and anti-adenoviral efficacy of topical SPL7013 in rabbit ocular models. In a tolerability study, rabbits were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Their eyes were graded using the Draize scale. In antiviral efficacy studies, HAdV5 inoculated eyes were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Eyes were cultured for the virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers were determined. There were no differences in Draize scores between 3% SPL7013 and vehicle on any day. Cidofovir produced significantly higher Draize scores on day 12 than SPL7013 and vehicle. The 3% SPL7013 and 0.5% cidofovir significantly reduced daily viral titers and positive cultures per total compared with vehicle on several different days. The 3% SPL7013 and 0.5% cidofovir significantly reduced the duration of HAdV5 shedding compared to vehicle. The 3% SPL7013 demonstrated significantly more antiviral activity compared with vehicle in the Ad5/NZW rabbit ocular model. The 3% SPL7013 induced “minimal” to “practically non-irritating” Draize scores in the ocular tolerability study. Further development of astodrimer sodium as a topical antiviral therapy for adenoviral ocular infections is indicated.     

Synthesis and antioxidant profile of all-rac-alpha-selenotocopherol

all-rac-alpha-Selenotocopherol (6c) has been synthesized in 11 steps in 6.6% total yield. Key steps include chloromethylation to approach the persubstituted aromatic 9b and cyclization of alcohol precursor 10 by radical homolytic substitution at selenium to form the selenotocopherol heterocycle. Determination of the OH bond dissociation enthalpy (BDE) of 6c by electron paramagnetic resonance (EPR) equilibration techniques gave a value of 78.1 +/- 0.3 kcal mol(-1), approximately 1 kcal mol(-1) higher than that of alpha-tocopherol. Kinetic studies performed by measuring oxygen uptake of the induced oxidation of styrene in the presence of an antioxidant showed that selenotocopherol (6c) was a slightly poorer inhibitor than alpha-tocopherol, in agreement with the BDE values. In contrast to simpler selenotocopherol analogues, 6c was not regenerable in the presence of a stoichiometric coreductant in a two-phase lipid peroxidation model.     

Thermoplastic starch films: DOE and O2PLS methodology for optimization and increased understanding of polymer processing

The combined effect of a plasticiser (glycerol) and a cross-linking agent (borax) on the mechanical properties of commercially extruded thermoplastic hydroxypropylated starch films was examined. The use of Design of Experiment (DOE) was demonstrated and used to predict and optimise formulations for a given set of material properties. As an extension to DOE, Orthogonal 2 Partial Least Squares (O2PLS) provided insight into joint correlations between the machine and transverse direction mechanical properties. Specific information regarding individual measurements or samples was also obtained with this analysis. O2PLS identified unique variables in individual compositions that were potentially incorrect measurements, or processing defects, which in turn can be used to aid quality control or processing optimisation with regards to DOE. Overall, DOE and O2PLS showed that within a starch borax-glycerol blend, borax increased mechanical strength and enhanced creep and recovery, whilst glycerol increased elongation and decreased modulus. There were competing interactions between the two dependent on concentration, and variation between machine and transverse properties was due to the extrusion induced molecular orientation of amylose. The optimum concentrations of borax and glycerol needed to achieve higher elongation, tensile strength, modulus and creep recovery than a control was found to be approximately 0.5% and 10%, respectively.     

Melting and thermal history of poly(hydroxybutyrate-co-hydroxyvalerate) using step-scan DSC

Melting behaviour and crystal morphology of poly(3-hydroxybutyrate) (PHB) and its copolymer of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with various hydroxyvalerate (HV) contents [5 wt.% (PHB5HV), 8 wt.% (PHB8HV) and 12 wt.% (PHB12HV)] have been investigated by conventional DSC, step-scan differential scanning calorimetry (SDSC) and hot-stage polarised optical microscopy (HSPOM). Crystallisation behaviour of PHB and its copolymers were investigated by SDSC. Thermal properties were investigated after different crystallisation treatments, fast, medium and slow cooling. Multiple melting peak behaviour was observed for all polymers. SDSC data revealed that PHB and its copolymers undergo melting–recrystallisation–remelting during heating, as evidenced by exothermic peaks in the IsoK baseline (non-reversing signal). An increase in degree of crystallinity due to significant melt–recrystallisation was observed for slow-cooled copolymers. PHB5HV showed different crystal morphologies for various crystallisation conditions. SDSC proved a convenient and precise method for measurement of the apparent thermodynamic specific heat (reversing signal) HSPOM results showed that the crystallisation rates and sizes of spherulites were significantly reduced as crystallisation rate increased.     

Isothermal crystallization studies of poly(butylene terephthalate) composites

Different crystallization kinetic models (Avrami and Tobin) have been applied to study the crystallization kinetics of virgin poly(butylene terephthalate) (PBT) and filled PBT systems under isothermal experimental conditions. The experimental data have been analyzed with a nonlinear, multivariable regression program. The kinetic parameters for the isothermal crystallization have been determined. The analysis results indicate that both models satisfactorily represent the isothermal crystallization kinetics. PBT crystallizes most slowly. The presence of nanoclays or nanofibers, added as fillers, enhances the crystallization rate of PBT composites. An analysis of the kinetic data with the Avrami and Tobin models has shown little change in the crystallization exponent compared with that of virgin PBT. The crystallization rate constant decreases with a rise in the temperature for the two models. This trend has been observed for similar polyester systems reported in the literature. The dispersion of the clay layers in the PBT nanocomposites has been characterized with wide‐angle X‐ray diffraction and transmission electron microscopy. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1344–1353, 2007     

The dynamics of water-protein interaction studied by ultrafast optical Kerr-effect spectroscopy

Changes in the ultrafast dynamics and terahertz Raman spectrum accompanying a helix-to-coil transition of a homo-polypeptide have been observed for the first time. Formation of the alpha-helix is associated with a shift to lower frequency of a broad Raman band attributable to solvent-peptide intermolecular hydrogen bonding. This band facilitates direct spectroscopic observation of so-called hydration water near a peptide and yields the first quantitative estimate of the time scale of the ultrafast dynamics in the solvation shell, which range from 0.18 to 0.33 ps (185-100 cm(-1)) depending on the secondary structure of the peptide. Such fast motions of solvent molecules have been referred to as the "lubricant of life" and are thought to play key roles in determining structure and activity of proteins.     

Biomolecular profiling of metastatic prostate cancer cells in bone marrow tissue using FTIR microspectroscopy: a pilot study

Prostate cancer (CaP) cells preferentially metastasise to the bone marrow, a microenvironment that plays a substantial role in the sustenance and progression of the CaP tumour. Here we use a combination of FTIR microspectroscopy and histological stains to increase molecular specificity and probe the biochemistry of metastatic CaP cells in bone marrow tissue derived from a limited source of paraffin-embedded biopsies of different patients. This provides distinction between the following dominant metabolic processes driving the proliferation of the metastatic cells in each of these biopsies: glycerophospholipid synthesis from triacylglyceride, available from surrounding adipocytes, in specimen 1, through significantly high (p ≤ 0.05) carbohydrate (8.23 ± 1.44 cm⁻¹), phosphate (6.13 ± 1.5 cm⁻¹) and lipid hydrocarbon (24.14 ± 5.9 cm⁻¹) signals compared with the organ-confined CaP control (OC CaP), together with vacuolation of cell cytoplasm; glycolipid synthesis in specimen 2, through significantly high (p ≤ 0.05) carbohydrate (5.51 ± 0.04 cm⁻¹) and high lipid hydrocarbon (17.91 ± 2.3 cm⁻¹) compared with OC CaP, together with positive diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells; glycolysis in specimen 3, though significantly high (p ≤ 0.05) carbohydrate (8.86 ± 1.78 cm⁻¹) and significantly lower (p ≤ 0.05) lipid hydrocarbon (11.67 ± 0.4 cm⁻¹) than OC CaP, together with negative diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells. Detailed understanding of the biochemistry underpinning the proliferation of tumour cells at metastatic sites may help towards refining chemotherapeutic treatment.     

Elevation of charring level of polyamide-6,6 films via ionic introduction of phosphoric acid and boric acid esters

Phosphorus and boron containing materials have the feature of increasing char formation, which can be effectively used as flame retardants especially in textiles. This paper discusses the ionic addition of phosphorus and boron esters to polyamide-6,6 (PA66), and its effect on the charring level. A mixture of phosphoric acid–boric acid ester at different degrees of esterification (ED) was prepared and two theoretical mechanisms for the esterification reaction were suggested. Ionically grafted polymer films were prepared by introducing the ester of highest ED to PA66–formic acid solution via three different processes: open air (cold) grafting, ultraviolet irradiation grafting, and hot vacuum oven grafting. Thermogravimetry was conducted for all synthesized esters and films, and the formation of new bonds between the ester and PA66 was verified using Fourier transform infrared spectroscopy.     

Modeling Biological Systems: The Belousov–Zhabotinsky Reaction

In this essay I examine the ways in which the Belousov–Zhabotinsky (BZ) reaction is being used by biologists to model a variety of biological systems and processes. The BZ reaction is characterized as a functional model of biological phenomena. It is able to play this role because, though based on very different substrates, the model and system modeled are examples of the same type of excitable medium. Lessons are drawn from this case about the relationships between the sciences of chemistry and biology.     

Photoelectron and electron energy loss spectra of epitaxial aluminum nitride

The valence bands of epitaxial layers of A1N were studied by ultraviolet photoelectron spectroscopy and electron energy loss spectroscopy. A self-consistent band structure was calculated and the resultant density of states compared with the UPS spectra. Qualitative agreement was good, with discrepancies arising primarily from the neglect of dipole matrix elements.