Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever

Published source: Bremner, S. A., Carey, I. M., DeWilde, S., Richards, N., Maier, W. C., Hilton, S. R., Strachan, D. P. and Cook, D. G. (2007), Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever. Clinical & Experimental Allergy, 37: 512–517. doi: 10.1111/j.1365-2222.2007.02697.

Bovine Serum Albumin Adsorbed PGA-co-PDL Nanocarriers for Vaccine Delivery via Dry Powder Inhalation

PURPOSE: Dry powder vaccine delivery via the pulmonary route has gained significant attention as an alternate route to parenteral delivery. In this study, we investigated bovine serum albumin (BSA) adsorbed poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL polymeric nanoparticles (NPs) within L-leucine (L-leu) microcarriers for dry powder inhalation. METHODS: NPs were prepared by oil-in-water single emulsion-solvent evaporation and particle size optimised using Taguchi’s design of experiment. BSA was adsorbed onto NPs at different ratios at room temperature. The NPs were spray-dried in aqueous suspension of L-leu (1:1.5) using a Büchi-290 mini-spray dryer. The resultant nanocomposite microparticles (NCMPs) were characterised for toxicity (MTT assay), aerosolization (Next Generation Impactor), in vitro release study and BSA was characterized using SDS-PAGE and CD respectively. RESULTSL NPs of size 128.50 ± 6.57 nm, PDI 0.07 ± 0.03 suitable for targeting lung dendritic cells were produced. BSA adsorption for 1 h resulted in 10.23 ± 1.87 μg of protein per mg of NPs. Spray-drying with L-leu resulted in NCMPs with 42.35 ± 3.17% yield. In vitro release study at 37°C showed an initial burst release of 30.15 ± 2.33% with 95.15 ± 1.08% over 48 h. Aerosolization studies indicated fine particle fraction (FPF%) dae < 4.46 μm as 76.95 ± 5.61% and mass median aerodynamic diameter (MMAD) of 1.21 ± 0.67 μm. The cell viability was 87.01 ± 14.11% (A549 cell line) and 106.04 ± 21.14% (16HBE14o- cell line) with L-leu based NCMPs at 1.25 mg/ml concentration after 24 h treatment. The SDS-PAGE and CD confirmed the primary and secondary structure of the released BSA. CONCLUSIONS: The results suggest that PGA-co-PDL/L-leu NCMPs may be a promising carrier for pulmonary vaccine delivery due to excellent BSA adsorption and aerosolization behaviour

Bovine serum albumin adsorbed PGA-CO-PDL nanocarriers for vaccine delivery via dry powder inhalation

Purpose: Dry powder vaccine delivery via the pulmonary route has gained significant attention as an alternate route to parenteral delivery. In this study, we investigated bovine serum albumin (BSA) adsorbed poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL polymeric nanoparticles (NPs) within L-leucine (L-leu) microcarriers for dry powder inhalation. Methods: NPs were prepared by oil-in-water single emulsion-solvent evaporation and particle size optimised using Taguchi's design of experiment. BSA was adsorbed onto NPs at different ratios at room temperature. The NPs were spray-dried in aqueous suspension of L-leu (1:1.5) using a Büchi-290 mini-spray dryer. The resultant nanocomposite microparticles (NCMPs) were characterised for toxicity (MTT assay), aerosolization (Next Generation Impactor), in vitro release study and BSA was characterized using SDS-PAGE and CD respectively. Results: NPs of size 128.50∈±∈6.57 nm, PDI 0.07∈±∈0.03 suitable for targeting lung dendritic cells were produced. BSA adsorption for 1 h resulted in 10.23∈±∈1.87 μg of protein per mg of NPs. Spray-drying with L-leu resulted in NCMPs with 42.35∈±∈3.17% yield. In vitro release study at 37°C showed an initial burst release of 30.15∈±∈2.33% with 95.15∈±∈1.08% over 48 h. Aerosolization studies indicated fine particle fraction (FPF%) dae∈<∈4.46 μm as 76.95∈±∈5.61% and mass median aerodynamic diameter (MMAD) of 1.21∈±∈0.67 μm. The cell viability was 87.01∈±∈14.11% (A549 cell line) and 106.04∈±∈21.14% (16HBE14o- cell line) with L-leu based NCMPs at 1.25 mg/ml concentration after 24 h treatment. The SDS-PAGE and CD confirmed the primary and secondary structure of the released BSA. Conclusions: The results suggest that PGA-co-PDL/L-leu NCMPs may be a promising carrier for pulmonary vaccine delivery due to excellent BSA adsorption and aerosolization behaviour

Dry powder pulmonary delivery of cationic PGA-co-PDL nanoparticles with surface adsorbed model protein.

Pulmonary delivery of macromolecules has been the focus of attention as an alternate route of delivery with benefits such as; large surface area, thin alveolar epithelium, rapid absorption and extensive vasculature. In this study, a model protein, bovine serum albumin (BSA) was adsorbed onto cationic PGA-co-PDL polymeric nanoparticles (NPs) prepared by a single emulsion solvent evaporation method using a cationic surfactant didodecyldimethylammonium bromide (DMAB) at 2% w/w (particle size: 128.64±06.01nm and zeta-potential: +42.32±02.70mV). The optimum cationic NPs were then surface adsorbed with BSA, NP:BSA (100:4) ratio yielded 10.01±1.19μg of BSA per mg of NPs. The BSA adsorbed NPs (5mg/ml) were then spray-dried in an aqueous suspension of L-leucine (7.5mg/ml, corresponding to a ratio of 1:1.5/NP:l-leu) using a Büchi-290 mini-spray dryer to produce nanocomposite microparticles (NCMPs) containing cationic NPs. The aerosol properties showed a fine particle fraction (FPF, dae<4.46μm) of 70.67±4.07% and mass median aerodynamic diameter (MMAD) of 2.80±0.21μm suggesting a deposition in the respiratory bronchiolar region of the lungs.The cell viability was 75.76±03.55% (A549 cell line) at 156.25μg/ml concentration after 24h exposure. SDS-PAGE and circular dichroism (CD) confirmed that the primary and secondary structure of the released BSA was maintained. Moreover, the released BSA showed 78.76±1.54% relative esterolytic activity compared to standard BSA

Reaction path modelling of in-situ mineralisation of CO2 at the CarbFix site at Hellisheidi, SW-Iceland

Results from injection of 175 tonnes of CO 2 into the basaltic subsurface rocks at the CarbFix site in SW-Iceland in 2012 show almost complete mineralisation of the injected carbon in less than two years (Matter et al., 2016; Snæbjörnsdóttir et al., 2017). Reaction path modelling was performed to illuminate the rate and extent of CO 2 -water-rock reactions during and after the injection. The modelling calculations were constrained by the compositions of fluids sampled prior to, during, and after the injection, as reported by Alfredsson et al. (2013) and Snæbjörnsdóttir et al. (2017). The pH of the injected fluid, prior to CO 2 dissolution was ∼9.5, whereas the pH of the background waters in the first monitoring well prior to the injections was ∼9.4. The pH of the sampled fluids used in the modelling ranged from ∼3.7 at the injection well to as high as 8.2 in the first monitoring well. Modelling results suggest that CO 2 -rich water-basalt interaction is dominated by crystalline basalt dissolution along a faster, high permeability flow path, but by basaltic glass dissolution along a slower, pervasive flow path through which the bulk of the injected fluid flows. Dissolution of pre-existing calcite at the onset of the injection does not have a net effect on the carbonation, but does contribute to a rapid early pH rise during the injection, and influences which carbonate minerals precipitate. At low pH, Mg, and Fe are preferentially released from crystalline basalts due to the higher dissolution rates of olivine, and to lesser extent pyroxene, compared to plagioclase and glass (Gudbrandsson et al., 2011). This favours the formation of siderite and Fe-Mg carbonates over calcite during early mineralisation. The model suggests the formation of the following carbonate mineral sequences: siderite at pH 5, and calcite at higher pH. Other minerals forming with the carbonates are Al- and Fe-hydroxides and chalcedony, and zeolites and smectites at elevated pH. The most efficient carbonate formation is when the pH is high enough for formation of carbonates, but not so high that zeolites and smectites start to form, which compete with carbonates over both cations and pore space. The results of reaction path modelling at the CarbFix site in SW-Iceland indicate that this “sweet spot” for mineralisation of CO 2 is at pH from ∼5.2 to 6.5 in basalts at low temperature (20–50 °C)

An accurate test for homogeneity of odds ratios based on Cochran's Q-statistic

Background: A frequently used statistic for testing homogeneity in a meta-analysis of K independent studies is Cochran's Q. For a standard test of homogeneity the Q statistic is referred to a chi-square distribution with K - 1 degrees of freedom. For the situation in which the effects of the studies are logarithms of odds ratios, the chi-square distribution is much too conservative for moderate size studies, although it may be asymptotically correct as the individual studies become large. Methods: Using a mixture of theoretical results and simulations, we provide formulas to estimate the shape and scale parameters of a gamma distribution to t the distribution of Q. Results: Simulation studies show that the gamma distribution is a good approximation to the distribution for Q. Conclusions: : Use of the gamma distribution instead of the chi-square distribution for Q should eliminate inaccurate inferences in assessing homogeneity in a meta-analysis. (A computer program for implementing this test is provided.) This hypothesis test is competitive with the Breslow-Day test both in accuracy of level and in power

Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al

Genotoxicity evaluation of the insecticide ethion in root of Allium cepa L.

In this study, the genotoxic effects of ethion were investigated in the mitotic cell division of Allium cepa. Primary roots of A. cepa were treated with various concentrations (25, 50, 75, and 100%) of ethion solutions for different duration of time. The result revealed that increase in the concentration and duration of treatment decreases the mitotic indices. 24 h treatment at 100% concentration of ethion induced lowest mitotic index (20.08%) than that of the control (36.37%). The percentage of chromosomal abnormalities in different mitotic stages was significantly generally higher than that of the control in all the treatment period and concentrations. These abnormalities appeared in various degrees depending on the treatment duration and concentrations of ethion. The abnormalities in dividing cell reached a maximum value of 11.30% after 12 h of treatment at 75% concentration. The type of abnormalitiesproduced were scattered prophase, non-synchronized condensation of chromosome, disturbed prophase, equatorial plate shifting, sticky chromosomes, C-metaphase and sticky metaphase. Overall, it can be concluded that ethion has a potential genotoxic effects on mitotic divisions in A. cepa root tip cells. So, it will be necessary to test the mutagenic potential of ethion on a more intensive and extensive basis especially on non-target systems before it is recommended for wider use in agriculturalfield

Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit.

The bacterial homologue of C4orf14, YqeH, has been linked to assembly of the small ribosomal subunit. Here, recombinant C4orf14 isolated from human cells, co-purified with the small, 28S subunit of the mitochondrial ribosome and the endogenous protein co-fractionated with the 28S subunit in sucrose gradients. Gene silencing of C4orf14 specifically affected components of the small subunit, leading to decreased protein synthesis in the organelle. The GTPase of C4orf14 was critical to its interaction with the 28S subunit, as was GTP. Therefore, we propose that C4orf14, with bound GTP, binds to components of the 28S subunit facilitating its assembly, and GTP hydrolysis acts as the release mechanism. C4orf14 was also found to be associated with human mitochondrial nucleoids, and C4orf14 gene silencing caused mitochondrial DNA depletion. In vitro C4orf14 is capable of binding to DNA. The association of C4orf14 with mitochondrial translation factors and the mitochondrial nucleoid suggests that the 28S subunit is assembled at the mitochondrial nucleoid, enabling the direct transfer of messenger RNA from the nucleoid to the ribosome in the organelle.Medical Research Council (MRC); Biotechnology and Biological Sciences Research Council (BBSRC); European Union; Academy of Finland (to H.M.C.). Funding for open access charge: MRC