Development and in vitro characterization of chitosan-based microspheres for nasal delivery of promethazine

Conventional and composed promethazine-loaded microspheres were prepared by spray drying of chitosan solution systems and double water-in-oil-in-water (W/O/W) emulsion systems, respectively. Double emulsions were prepared in two different feed concentrations, with chitosan dissolved in both water phases, and ethylcellulose dissolved in oil phase. Swelling and bioadhesive properties of the microspheres depended on the chitosan content, type and the feed concentration of spray-dried system. Results obtained suggested that better ethylcellulose microcapsules with promethazine in the chitosan matrix were formed when less concentrated emulsion systems were spray-dried. Thus, in case of such a system, with ethylcellulose/chitosan weight ratio of 1:2, prolonged promethazine release was obtained.     

Recombinant adeno-associated virus targets passenger gene expression to cones in primate retina

Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy of photoreceptor-based diseases. Previous studies have demonstrated that rAAV serotypes 2 and 5 can transduce both rod and cone photoreceptors in rodents and dogs, and it can target rods, but not cones in primates. Here we report that using a human cone-specific enhancer and promoter to regulate expression of a green fluorescent protein (GFP) reporter gene in an rAAV-5 vector successfully targeted expression of the reporter gene to primate cones, and the time course of GFP expression was able to be monitored in a living animal using the RetCam II digital imaging system.     

Hot Hydrogen Exposure Degradation of the Strength of Mullite

Near-stoichiometric mullite (3Al₂O₃2SiO₂) that contained small amounts of calcium and magnesium was exposed to pure dry hydrogen gas at elevated temperatures. Exposure temperatures were 1050° and 1250°C, and exposure times were up to 500 h. Preferential attack of the aluminosilicate glass that was present in the grain boundaries of the mullite occurred after 125 h at 1250°C. Hydrogen scrubbing of the silica from the glassy grain boundaries and the mullite grains yielded a porous alumina-rich surface. The room-temperature strength increased after short exposure times at 1250°C (up to 125 h) and then decreased by 53% after exposure for 500 h. At 1050°C, all exposure times (25-500 h) decreased the strength. The room-temperature strength of mullite decreased 22% after 500 h in hydrogen at 1050°C. We also observed a rapid 25% strength loss after short exposure times at 1050°C, which was attributed to the calcium/hydrogen-assisted crystallization of the glassy grain-boundary phase.     

Estimation of impact-induced damage in CFRR laminates through ultrasonic imaging

Ultrasonic C-scans are used frequently to detect defects in composite components caused during fabrication and damage resulting from service conditions. Evaluation and characterization of defects and damage require experience and good understanding of the composites. Under low-velocity impact loading delamination is observed to be a major failure mode. In this paper, the results of extensive experimental work on damage of carbon fiber reinforced plastic (CFRP) laminates due to low-velocity impact are presented. The study was carried out on 10 different layups over four different thickness. Both drop-weight and projectile impacts simulating practical conditions like tool-drop and runway debris, respectively, were carried out at energy levels varying from 3 to 30 J. The ensuing delamination damage was determined by ultrasonic: C-scans using the pulse-echo immersion method for both projected and layer-wise distribution. While projected delamination was obtained by placing a gate over the backwall echo, layerwise distribution was obtained by successive time delay from the frontwall to the backwall echo covering each interface. Delamination areas were quantified accurately by processing the raw image data using a digital image processing technique. Based on the data obtained an empirical relation was established between the delamination area and the impact energy.     

Structure,growth, and morphology in para nitroaniline dispersed polymethyl methacrylate guest‐host NLO composites

The structure, growth, and morphology of composite films made by dispersing para nitroaniline (PNA) in poly(methyl methacrylate) (PMMA) was investigated with respect to different crystallization methods, composition, and application of electric field. The wide‐angle X‐ray diffraction scans showed large variations in intensity of different reflections, especially the Okl with composition and in the presence of an electric field. In addition, it also showed the occurrence of a new crystalline structure, possibly due to complex formation between PNA and PMMA. The presence of this complex was further confirmed by infrared spectroscopy and thermal analysis. In a certain range of composition (30 to 40 % PNA), spherulitic morphology was observed, which otherwise consisted of needle‐shaped crystals dispersed in amorphous matrix. The transparency of these films also depended strongly on the crystallization conditions, and highly transparent films could be obtained, even at high PNA content by application of electric field. These various results could be explained on the basis of the intermolecular interaction between PNA and PMMA, as well as preferential growth direction and orientation of the PNA crystals. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 3522–3534, 1999     

Effect of Heat Processing on IgE Reactivity and Cross‐Reactivity of Tropomyosin and Other Allergens of Asia‐Pacific Mollusc Species: Identification of Novel Sydney Rock Oyster Tropomyosin Sac g 1

1 Scope

Shellfish allergy is an increasing global health priority, frequently affecting adults. Molluscs are an important shellfish group causing food allergy but knowledge of their allergens and cross‐reactivity is limited. Optimal diagnosis of mollusc allergy enabling accurate advice on food avoidance is difficult. Allergens of four frequently ingested Asia‐Pacific molluscs are characterized: Sydney rock oyster (Saccostrea glomerata), blue mussel (Mytilus edulis), saucer scallop (Amusium balloti), and southern calamari (Sepioteuthis australis), examining cross‐reactivity between species and with blue swimmer crab tropomyosin, Por p 1.

2 Methods and results

IgE ELISA showed that cooking increased IgE reactivity of mollusc extracts and basophil activation confirmed biologically relevant IgE reactivity. Immunoblotting demonstrated strong IgE reactivity of several proteins including one corresponding to heat‐stable tropomyosin in all species (37–40 kDa). IgE‐reactive Sydney rock oyster proteins were identified by mass spectrometry, and the novel major oyster tropomyosin allergen was cloned, sequenced, and designated Sac g 1 by the IUIS. Oyster extracts showed highest IgE cross‐reactivity with other molluscs, while mussel cross‐reactivity was weakest. Inhibition immunoblotting demonstrated high cross‐reactivity between tropomyosins of mollusc and crustacean species.

3 Conclusion

These findings inform novel approaches for reliable diagnosis and improved management of mollusc allergy.     

Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease

Research by Klein and co-workers suggests that the inhibition of GSK-3beta by small molecules may offer an important strategy in the treatment of a number of central nervous system (CNS) disorders including Alzheimer's disease, Parkinson's disease, and bipolar disorders. Based on results from kinase-screening assays that identified a staurosporine analogue as a modest inhibitor of GSK-3beta, a series of 3-indolyl-4-indazolylmaleimides was prepared for study in both enzymatic and cell-based assays. Most strikingly, whereas we identified ligands having poor to high potency for GSK-3beta inhibition, only ligands with a Ki value of less than 8 nM, namely maleimides 18 and 22, were found to inhibit Tau phosphorylation at a GSK-3beta-specific site (Ser 396/404). Accordingly, maleimides 18 and 22 may protect neuronal cells against cell death by decreasing the level of alpha-Syn protein expression. We conclude that the GSK-3beta inhibitors described herein offer promise in defending cells against MPP+-induced neurotoxicity and that such compounds will be valuable to explore in animal models of Parkinson's disease as well as in other Tau-related neurodegenerative disease states.     

Contribution of first- versus second-generation products to secondary organic aerosols formed in the oxidation of biogenic hydrocarbons

Biogenic hydrocarbons emitted by vegetation are important contributors to secondary organic aerosol (SOA), but the aerosol formation mechanisms are incompletely understood. In this study, the formation of aerosols and gas-phase products from the ozonolysis and photooxidation of a series of biogenic hydrocarbons (isoprene, 8 monoterpenes, 4 sesquiterpenes, and 3 oxygenated terpenes) are examined. By comparing aerosol growth (measured by Differential Mobility Analyzers, DMAs) and gas-phase concentrations (monitored by a Proton Transfer Reaction Mass Spectrometer, PTR-MS), we study the general mechanisms of SOA formation. Aerosol growth data are presented in terms of a "growth curve", a plot of aerosol mass formed versus the amount of hydrocarbon reacted. From the shapes of the growth curves, it is found that all the hydrocarbons studied can be classified into two groups based entirely on the number of double bonds of the hydrocarbon, regardless of the reaction systems (ozonolysis or photooxidation) and the types of hydrocarbons studied: compounds with only one double bond and compounds with more than one double bond. For compounds with only one double bond, the first oxidation step is rate-limiting, and aerosols are formed mainly from low volatility first-generation oxidation products; whereas for compounds with more than one double bond, the second oxidation step may also be rate-limiting and second-generation products contribute substantially to SOA growth. This behavior is characterized by a vertical section in the growth curve, in which continued aerosol growth is observed even after all the parent hydrocarbon is consumed.     

Ergot alkaloids in cereal products: results from the Bavarian Health and Food Safety Authority

The danger of ergot alkaloids has been well known for centuries. The origin and toxicology of these compounds have been clarified and flour mills assure us that they have mastered the problem technologically. Nevertheless, one can find food products with sometimes relatively high contents of these toxic alkaloids. Here we report on our experiences and results of an LC-MS/MS-method which we have developed to determine ergot alkaloids and which was applied to commercial products during the past two years.