In Vivo Sustained Release of the Retrograde Transport Inhibitor Retro-2.1 Formulated in a Thermosensitive Hydrogel

A recently developed inhibitor of retrograde transport, namely Retro-2.1, proved to be a potent and broad-spectrum lead in vitro against intracellular pathogens, such as toxins, parasites, intracellular bacteria and viruses. To circumvent its low aqueous solubility, a formulation in poly(ethylene glycol)-block-poly(D,L)lactide micelle nanoparticles was developed. This formulation enabled the study of the pharmacokinetic parameters of Retro-2.1 in mice following intravenous and intraperitoneal injections, revealing a short blood circulation time, with an elimination half-life of 5 and 6.7 h, respectively. To explain the poor pharmacokinetic parameters, the metabolic stability of Retro-2.1 was studied in vitro and in vivo, revealing fast cytochrome-P-450-mediated metabolism into a less potent hydroxylated analogue. Subcutaneous injection of Retro-2.1 formulated in a biocompatible and bioresorbable polymer-based thermosensitive hydrogel allowed for sustained release of the drug, with an elimination half-life of 19 h, and better control of its metabolism. This study provides a guideline on how to administer this promising lead in vivo in order to study its efficacy.     

Acute exposure to silica nanoparticles enhances mortality and increases lung permeability in a mouse model of Pseudomonas aeruginosa pneumonia

Background

The lung epithelium constitutes the first barrier against invading pathogens and also a major surface potentially exposed to nanoparticles. In order to ensure and preserve lung epithelial barrier function, the alveolar compartment possesses local defence mechanisms that are able to control bacterial infection. For instance, alveolar macrophages are professional phagocytic cells that engulf bacteria and environmental contaminants (including nanoparticles) and secrete pro-inflammatory cytokines to effectively eliminate the invading bacteria/contaminants. The consequences of nanoparticle exposure in the context of lung infection have not been studied in detail. Previous reports have shown that sequential lung exposure to nanoparticles and bacteria may impair bacterial clearance resulting in increased lung bacterial loads, associated with a reduction in the phagocytic capacity of alveolar macrophages.

Results

Here we have studied the consequences of SiO₂ nanoparticle exposure on Pseudomonas aeruginosa clearance, Pseudomonas aeruginosa-induced inflammation and lung injury in a mouse model of acute pneumonia. We observed that pre-exposure to SiO₂ nanoparticles increased mice susceptibility to lethal pneumonia but did not modify lung clearance of a bioluminescent Pseudomonas aeruginosa strain. Furthermore, internalisation of SiO₂ nanoparticles by primary alveolar macrophages did not reduce the capacity of the cells to clear Pseudomonas aeruginosa. In our murine model, SiO₂ nanoparticle pre-exposure preferentially enhanced Pseudomonas aeruginosa-induced lung permeability (the latter assessed by the measurement of alveolar albumin and IgM concentrations) rather than contributing to Pseudomonas aeruginosa-induced lung inflammation (as measured by leukocyte recruitment and cytokine concentration in the alveolar compartment).

Conclusions

We show that pre-exposure to SiO₂ nanoparticles increases mice susceptibility to lethal pneumonia but independently of macrophage phagocytic function. The deleterious effects of SiO₂ nanoparticle exposure during Pseudomonas aeruginosa-induced pneumonia are related to alterations of the alveolar-capillary barrier rather than to modulation of the inflammatory responses.

Electronic supplementary material

The online version of this article (doi:10.1186/s12989-014-0078-9) contains supplementary material, which is available to authorized users.     

Lifetimes of organic photovoltaics: photochemistry, atmosphere effects and barrier layers in ITO-MEHPPV:PCBM-aluminium devices

Large area polymer photovoltaic cells based on poly[(2-methoxy-5-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) and [6,6]-phenyl-C₆₁-butyric acid methyl ester (PCBM) were prepared. The lifetimes of the photovoltaic cells were studied in terms of the atmosphere, handling, electrode treatment, mode of preparation and barrier layers by recording the short circuit current as a function of time. Two exponential fits to the decay curves allowed for the extraction of the time constants for different degradation processes. For the periods of time studied here (24–300 h), the decay curves could be fitted with two exponential functions. Common to the preparations were that the first half-life remained short and was independent of the presence of oxygen. When fullerenes were employed by sublimation of a layer of C₆₀ or as the soluble PCBM, the first half-life was an order of magnitude longer and depended on the presence of oxygen. By employing different barrier layers, we found the first half-life to be linked to the aluminium polymer interface and ascribe it to a photochemical reaction between the organic material and the reactive aluminium at the interface. The second and longer half-life was found to depend on the presence of oxygen. We also discuss our findings of the short lifetimes for organic photovoltaics under AM1.5 illumination in the context of future applications.     

综合技术优势帮助提高生产率和效率

ABB Cellier在为全球造纸行业提供涂料制备服务领域己拥有超过50多年的经验一，这些复杂装置旨在优化化学品的使用，在符合印刷适性和亮度等技术要求的同时提高质量，以便为原纸带来更高的附加值，并改善涂布机的运行性能。     

Impairment of consciously controlled use of memory in schizophrenia.

Recent studies of memory in schizophrenia have shown that explicit but not implicit memory performance is impaired. The hypothesis that schizophrenia is associated with a failure of consciously but not unconsciously (automatic) controlled influence of memory on performance was tested using a procedure providing uncontaminated estimates of consciously controlled and automatic memory processes (i.e., the process-dissociation procedure in a stem completion task). Performance of 35 patients with schizophrenia was compared with that of 35 normal participants. Consciously controlled use but not automatic influences of memory was significantly lower in patients with schizophrenia than in controls. Consciously controlled use of memory was negatively and significantly correlated with positive symptoms of schizophrenia. Schizophrenia differentially affects 2 types of memory processes: It impairs consciously controlled use of memory but spares automatic influences. Positive symptoms could reflect the lack of control from higher level conscious processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nanostructured Carbons as Platinum Catalyst Supports for Proton Exchange Membrane Fuel Cell Electrodes

To improve mass transport in the catalytic layers of proton exchange membrane fuel cells, the usual Pt catalyst support (carbon blacks) can be advantageously replaced by carbon aerogels or xerogels. The pore texture of such materials can indeed be tailored, which enables choosing an adequate pore texture minimizing diffusional limitations within the catalytic layers.     

Catalytic study of SOFC electrode materials in engine exhaust gas atmosphere

A single chamber solid oxide fuel cell (SC-SOFC) is a device able to produce electricity from a mixture of hydrocarbons and oxidant. An innovative application of this system would be to recover energy from exhaust gas of a thermal engine. This paper presents a study of stability and catalytic behaviour of electrode materials composing the cell in a mixture of hydrocarbons (propane, propene), oxygen, carbon monoxide, carbon dioxide, hydrogen and water corresponding to a composition of exhaust gas. A screening of four cathode materials was done, some well-known materials in literature and leading to highest performances such as La_0.6Sr_0.4Co_0.2Fe_0.8O_3?δ (LSCF), Sm_0.5Sr_0.5CoO_3?δ and Ba_0.5Sr_0.5Co_0.8Fe_0.2O_3?δ and a last one Pr₂NiO_4+δ (PNO) very promising for conventional SOFCs. Anode material was a cermet composed of nickel and Ce_0.9Gd_0.1O_1.95 which was also selected as the electrolyte material. Chemical stability tests and catalytic activity studies in the gas mixture were performed on the raw materials and have led to a first selection among cathodes. Two hydrocarbons/oxygen ratios (R = HC/O₂) were investigated for materials tests considering the gas mixture stability at high temperature (600 °C): R = 0.21 and 0.44. LSCF and PNO were considered as the most stable cathode materials, besides LSCF demonstrated a lower catalytic activity towards hydrocarbon partial oxidation than PNO especially for the R = 0.44 ratio. As for the anode side, nickel was tested regarding its catalytic activity towards hydrocarbons oxidation. It exhibited catalytic activity towards hydrocarbons partial oxidation, especially for the oxygen-lean ratio (0.44), which gradually decreased while lowering temperature from 620 to 450 °C.     

Microsphere‐Mediated Protein Delivery into Cells

Delivering the goods : By coupling proteins to varyingly sized polymeric microspheres, it is possible to deliver them to cells in an easy and effective way. For this study a fluorescent protein (EGFP) and a functional enzyme (β‐galactosidase) were coupled to these particles. Evaluation of the cellular uptake after “beadfection” shows that the functionality and activity of these proteins were not adversely affected through coupling to the carrier system; this shows that their functional structure is retained.

     

Effect of skim milk treated with high hydrostatic pressure on permeate flux and fouling during ultrafiltration

Ultrafiltration (UF) is largely used in the dairy industry to generate milk and whey protein concentrate for standardization of milk or production of dairy ingredients. Recently, it was demonstrated that high hydrostatic pressure (HHP) extended the shelf life of milk and improved rennet coagulation and cheese yield. Pressurization also modified casein micelle size distribution and promoted aggregation of whey proteins. These changes are likely to affect UF performance. Consequently, this study determined the effect of skim milk pressurization (300 and 600 MPa, 5 min) on UF performance in terms of permeate flux decline and fouling. The effect of HHP on milk proteins was first studied and UF was performed in total recycle mode at different transmembrane pressures to determine optimal UF operational parameters and to evaluate the effect of pressurization on critical and limiting fluxes. Ultrafiltration was also performed in concentration mode at a transmembrane pressure of 345 kPa for 130 or 140 min to evaluate the decline of permeate flux and to determine fouling resistances. It was observed that average casein micelle size decreased by 32 and 38%, whereas β-lactoglobulin denaturation reached 30 and 70% at 300 and 600 MPa, respectively. These results were directly related to UF performance because initial permeate fluxes in total recycle mode decreased by 25% at 300 and 600 MPa compared with nonpressurized milk, critical flux, and limiting flux, which were lower during UF of milk treated with HHP. During UF in concentration mode, initial permeate fluxes were 30% lower at 300 and 600 MPa compared with the control, but the total flux decline was higher for nonpressurized milk (62%) compared with pressure-treated milk (30%). Fouling resistances were similar, whatever the treatment, except at 600 MPa where irreversible fouling was higher. Characterization of the fouling layer showed that caseins and β-lactoglobulin were mainly involved in membrane fouling after UF of pressure-treated milk. Our results demonstrate that HHP treatment of skim milk drastically decreased UF performance.