Behaviour of helium after implantation in molybdenum

This study deals with the behaviour of helium in a molybdenum liner dedicated to the retention of fission products. More precisely this work contributes to evaluate the release of implanted helium when the gas has precipitated into nanometric bubbles close to the free surface. A simple model dedicated to calculate the helium release in such a condition is presented. The specificity of this model lays on the assumption that the gas is in equilibrium with a simple distribution of growing bubbles. This effort is encouraging since the calculated helium release fits an experimental dataset with a set of parameters in good agreement with the literature.     

Coffee Antioxidant Properties: Effects of Milk Addition and Processing Conditions

ABSTRACT: In the human diet, coffee is the major source of caffeoyl-quinic acids known as powerful antioxidants. The aim of this study was to assess the effect of usual coffee consumption, such as the addition of milk, and of processing conditions, such as spray-drying, on beverage antioxidant power and potential polyphenol bioavailability impairments. When 25% milk was added to coffee, up to 40% of coffee chlorogenic acid were found to be bound to dairy proteins, using an ultrafiltration technique. However, neither milk addition nor spray-drying had a significant effect on beverage antioxidant power, evaluated using 2,2-diphenyl-1-pycrylhydrazyl (DPPH), 2-2'-azobis (2-amidinopropane) dihydrochloride (AAPH), and total antioxidant capacity (TAC) tests. Moreover, these interactions tended to decrease during in vitro gastric and intestinal digestion, thus suggesting that interactions between chlorogenic acid and milk proteins in coffee and milk beverage may not have any significant effect on coffee antioxidant power before and after consumption.     

8-(3-Chlorostyryl)caffeine (CSC) is a selective A2-adenosine antagonist in vitro and in vivo

An adenosine antagonist, 8-(3-chlorostyryl)caffeine (CSC), was shown previously to be 520-fold selective for A2a-adenosine receptors in radioligand binding assays in the rat brain. In reversing agonist effects on adenylate cyclase, CSC was 22-fold selective for A2a receptors in rat phenochromocytoma cells (Kb 60 nM) vs. A1 receptors in rat adipocytes (Kb 1.3 microM). Administered i.p. in NIH mice at a dose of 1 mg/kg, CSC shifted the curve for locomotor depression elicited by the A2a-selective agonist APEC to the right (ED50 value for APEC shifted from 20 micrograms/kg i.p. to 190 micrograms/kg). CSC had no effect on locomotor depression elicited by an ED50 dose of the A1-selective agonist CHA. CSC alone at a dose of 5 mg/kg stimulated locomotor activity by 22% over control values. Coadministration of CSC and the A1-selective antagonist CPX, both at non-stimulatory doses, increased activity by 37% (P < 0.001) over CSC alone, suggesting a behavioral synergism of A1- and A2-antagonist effects in the CNS.     

Energy dispersive analysis of X-rays study of the distribution of chlorhexidine diacetate and cetylpyridinium chloride on the Pseudomonas aeruginosa bacteriophage F116

Using an energy dispersive analyser of X-rays fitted to a scanning electron microscope, chlorhexidine was shown not to bind onto F116 bacteriophage, unlike cetylpyridinium chloride, which possibly penetrated the phage. This could explain the difference in viricidal activity between the two compounds.     

Effect of the cascade energy on defect production in uranium dioxide

The primary damage induced by a displacement cascade in a pure uranium dioxide matrix was investigated using classical molecular dynamics simulations. Cascades were initiated by accelerating a uranium primary knock-on atom (PKA) to a kinetic energy ranging from 1 keV to 80 keV inside a perfect UO₂ lattice at low temperature (300 K and 700 K). There is little effect of temperature in the temperature range studied. Following the cascade event, the damage level, defined as the total number of defects irrespective of whether they form clusters or not, is proportional to the initial kinetic energy of the PKA, in agreement with the literature relating to other materials. The linear dependence of damage upon initial PKA energy results from the formation of subcascades at high energy and constitutes a simple law which can be applied to any material and used in order to extrapolate molecular dynamics results to high energy PKAs. The nature of irradiation induced defects has also been studied as a function of the cascade energy.     

An O-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat

Sepsis in the young population, which is particularly at risk, is rarely studied. O-GlcNAcylation is a post-translational modification involved in cell survival, stress response and metabolic regulation. O-GlcNAc stimulation is beneficial in adult septic rats. This modification is physiologically higher in the young rat, potentially limiting the therapeutic potential of O-GlcNAc stimulation in young septic rats. The aim is to evaluate whether O-GlcNAc stimulation can improve sepsis outcome in young rats. Endotoxemic challenge was induced in 28-day-old rats by lipopolysaccharide injection (E. Coli O111:B4, 20 mg·kg⁻¹) and compared to control rats (NaCl 0.9%). One hour after lipopolysaccharide injection, rats were randomly assigned to no therapy, fluidotherapy (NaCl 0.9%, 10 mL·kg⁻¹) ± NButGT (10 mg·kg⁻¹) to increase O-GlcNAcylation levels. Physiological parameters and plasmatic markers were evaluated 2h later. Finally, untargeted mass spectrometry was performed to map cardiac O-GlcNAcylated proteins. Lipopolysaccharide injection induced shock with a decrease in mean arterial pressure and alteration of biological parameters (p < 0.05). NButGT, contrary to fluidotherapy, was associated with an improvement of arterial pressure (p < 0.05). ATP citrate lyase was identified among the O-GlcNAcylated proteins. In conclusion, O-GlcNAc stimulation improves outcomes in young septic rats. Interestingly, identified O-GlcNAcylated proteins are mainly involved in cellular metabolism.     

Chlorogenic acid is poorly absorbed, independently of the food matrix: A Caco-2 cells and rat chronic absorption study

According to epidemiologic studies, dietary phenolic antioxidants, such as chlorogenic acid (CQA), could prevent coronary heart diseases and some cancers. Coffee is the main source of CQA in the human diet. The aim of this study was to assess the effect of usual coffee consumption conditions, such as the addition of milk, on CQA bioavailability. Interactions between CQA and milk proteins were shown, using an ultrafiltration technique. These interactions proved to be slightly disrupted during an in vitro digestion process. CQA absorption and bioavailability were then studied in vitro using a Caco-2 cell model coupled with an in vitro digestion process, and in vivo, in a chronic supplementation study in which rats were fed daily coffee or coffee and milk for 3 weeks. Both experiments showed that CQA absorption under its native form is weak, but unmodified by the addition of milk proteins, and slightly reduced by the addition of Maillard reaction products. These data show that there are some interactions between coffee phenolics and milk proteins, but these have no significant effect on CQA bioavailability from coffee in the rat. CQA is poorly absorbed under its native form in the body, when ingested in a realistic food matrix.     

Speciation of new tri- and tetra-glucoconjugated tetrapyrrolic macrocycles (porphyrins and chlorins): an electronic molecular spectroscopy study

In this work, we study the physicochemical properties of some newly developed glycoconjugated photosensitizers that can be used in photodynamic therapy (PDT) of cancers: meso-tri- and tetra-(meta-O-beta-D-glucosyloxyphenyl)porphyrins and meso-, tri-, and tetra-(meta-O-beta-D-glucosyloxyphenyl)chlorins. Their properties are compared to the non-glycosylated hydroxylated parent compounds meso-tetra-(meta-hydroxyphenyl) porphyrin and meso-tetra-(meta-hydroxyphenyl)chlorin. It was found that at the ground state, all porphyrins present, independent of the substitution, have the same mean ionization constant (pKa = 2.7), corresponding to two indistiguishable steps of protonation of tetrapyrrolic nitrogens. On the other hand, in the case of chlorins, one proton process can be observed and the corresponding nitrogen exhibits a slightly superior basicity (pKa = 3.0) with respect to porphyrins. Hydroxylated compounds present a second transition at high pH corresponding to the ionization of phenol groups (pKa = 10.5). Consequently, all photosensitizers are not charged at physiological pH (approximately 7.4), and so the ionization process does not influence their activity in biological media. Ionization induces very important variations in photosensitizer absorption and emission spectra. For example, absorption in the red region (band V), one of the most important characteristics of a good photosensitizer, is only important for diprotonated porphyrins and neutral chlorins. As far as fluorescence emission is concerned, neutral chlorins are almost six times more fluorescent than the corresponding neutral porphyrins (phi(chlorin)/phi(porphyrin) approximately = 6). It should be emphasized that the spectra modifications induced by pH variations can find interesting applications in the optimization of visible and fluorescence detection in high-performance liquid chromatography (HPLC) as well as in the development of direct, rapid fluorimetric analytical methods.     

Risk Mitigation of Immunogenicity: A Key to Personalized Retinal Gene Therapy

Gene therapy (GT) for ocular disorders has advanced the most among adeno-associated virus (AAV)-mediated therapies, with one product already approved in the market. The bank of retinal gene mutations carefully compiled over 30 years, the small retinal surface that does not require high clinical vector stocks, and the relatively immune-privileged environment of the eye explain such success. However, adverse effects due to AAV-delivery, though rare in the retina have led to the interruption of clinical trials. Risk mitigation, as the key to safe and efficient GT, has become the focus of ‘bedside-back-to-bench’ studies. Herein, we overview the inflammatory adverse events described in retinal GT trials and analyze which components of the retinal immunological environment might be the most involved in these immune responses, with a focus on the innate immune system composed of microglial surveillance. We consider the factors that can influence inflammation in the retina after GT such as viral sensors in the retinal tissue and CpG content in promoters or transgene sequences. Finally, we consider options to reduce the immunological risk, including dose, modified capsids or exclusion criteria for clinical trials. A better understanding and mitigation of immune risk factors inducing host immunity in AAV-mediated retinal GT is the key to achieving safe and efficient GT.