Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn’s disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 10⁹/L, respectively, to ≈13 days (both HR and RR) at 350 × 10⁹/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2.     

Synthesis, structure and catalytic properties of Fe-substituted barium hexaaluminates

A sol–gel method using Ba and Al isopropylates and iron nitrate has been used to synthesise barium hexaaluminate partially substituted with iron. After calcination under oxygen at 1200°C the -alumina structure was obtained. Formation of the mixed BaFe_xAl_12-xO₁₉ phase occurred for x=1–4. XRD measurements showed a good crystallinity of the structure and expansion of unit cell parameters due to the presence of larger Fe³⁺ ions substituting Al³⁺ ones in octahedral sites only. Mössbauer spectroscopy revealed that Fe³⁺ ions are present in four different octahedral sites slightly distorted. Catalytic activity in methane combustion showed that an optimum was obtained for solid containing 2 Fe ions per unit cell: the increase of the amount of introduced iron was counterbalanced by the decrease of specific surface area. Intrinsic activities have been calculated for the four solids in both the fresh and aged states. It is observed that increasing iron content increases relative activities in the same ratio as the populations of iron located in two sites as deduced from Mössbauer spectroscopy. It is then tentatively assumed that activity is attributed to octahedrally coordinated Fe³⁺ ions in some specific sites.     

Characterisation,by the PIXE Method,of Trace Elements During Physicochemical Reactions at the Periphery of Bioactive Glass Pastilles in Contact with Biological Fluids

Abstract

The prerequisite for bioactive glasses to bond to living bone is the formation of biologically active apatites on their surface in the body. Reactions and bioactivity mechanisms between bioactive glasses and bone depend on the glass composition. We study a glass in the SiO₂‐Na₂O‐CaO‐P₂O₅‐K₂O‐Al₂O₃‐MgO system. To characterise physicochemical reactions at the materials periphery, we immersed the glass pastilles into biological fluids for periods of 5, 10, and 20 days. The surface changes were studied at the micrometer scale by a Particle Induced X‐ray Emission (PIXE) method associated with Rutherford Backscattering Spectroscopy (RBS). After 20 days of immersion, elemental maps showed the formation of a calcium‐phosphate layer at the surface of the glass pastilles. The thickness of this layer was around 15 µm. Thanks to the PIXE method, we demonstrated the presence of traces of Mg in this layer. The glass doped with MgO leads to the formation of an apatite which incorporates magnesium. Formation of this Ca‐P‐Mg layer represents the bioactive properties of the studied glass. This biologically active layer improves the properties of the glass and will permit a chemical bond between the ceramic and bone.     

Phosphonic acid‐containing polysulfones as anticorrosive layers

As a part of research work to elaborate polymeric materials for metal corrosion protection, we have developed a new family of phosphonic acid‐containing polymers. The synthesis and the characterization of polysulfones bearing alkyl phosphonate ester side groups are first described. These polymers are synthesized by direct polycondensation of a phosphonate ester‐containing bisphenol by aromatic nucleophilic substitution. The physicochemical properties of the resulting polymers are described. Acidic hydrolysis of phosphonate esters results in the formation of phosphonic acid groups. A series of phosphonic acid‐containing polysulfones is therefore obtained and characterized. A preliminary evaluation of the anticorrosive properties of these polymers is described. In 0.25M Na₂SO₄ solution, the corrosion rate of a polymer‐coated mild steel sample is much lower than of the free metal substrate. These results suggest that phosphonic acid‐containing polysulfones might be interesting as anticorrosive coatings. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41890.     

Microwave-assisted synthesis of tetrasubstituted aryl imidazole based polymers via cascade polycondensation process

Poly(Tetrasubstituted Aryl Imidazole)s (PTAIs), a new class of poly(heteroaromatic) polymers was prepared via a cascade polycondensation process, under microwave irradiation. These polymers were obtained by the tetrasubstituted aryl imidazole ring formation involving bis(aryl α-diketone)s, bis(arylaldehyde)s, mono(arylamine)s and ammonium acetate. The polymerization performed under microwave irradiation allowed to get high molecular weight PTAIs in very short reaction times. The chemical structure of these PTAIs was confirmed by NMR spectroscopy. Thermogravimetric analyses (TGA) showed a very good grade of thermal stability of these polymers. Glass transition temperatures (T_g) of PTAIs ranging from 155 °C to 265 °C were determined by Differential Scanning Calorimetry (DSC).     

Optimization of Combined Microwave–Hot Air Roasting of Malt Based on Energy Consumption and Neo-Formed Contaminants Content

ABSTRACT: To produce specialty malt, malts were roasted by combined microwave–hot air at various specific microwave powers (SP = 2.5 to 3 W/g), microwave heating times (t_mw = 3.3 to 3.5 min), oven temperatures (T_oven = 180 to 220 °C), and oven heating times (t_oven = 60 to 150 min). The response variables, color, energy consumption by microwave (E_mw) and oven (E_oven), total energy consumption (E_tot), quantity of neo-formed contaminants (NFCs), which include hydroxymethylfurfural, furfural, furan, and acrylamide were determined. Response surface methodology (RSM) was performed to analyze and predict the optimum conditions for the specialty malt. Production using combined microwave–hot air roasting process based on minimum energy consumption and level of NFCs. At 95% confident level, SP, T_oven, and t_oven were the most influencing effects with regard to E_tot, whereas t_mw did not affect E_tot. T_oven and t_oven significantly affected malt color. Only T_oven significantly influenced the NFCs content. The optimum parameters were: SP = 2.68 W/g for 3.44 min, T_oven = 206 °C for 136 min for coffee malt, SP = 2.5 W/g for 3.48 min, T_oven = 214 °C for 136 min for chocolate malt, and SP = 2.5 W/g for 3.48 min, T_oven = 211 °C for 150 min for black malt. Comparing with conventional process, combined microwave–hot air reduced E_tot by approximately 40%, 26%, and 26% for coffee, chocolate, and black malts, respectively, and reduced HMF, furfural, furan, and acrylamide contents by 40%, 18%, 23%, and 95%, respectively, for black malt. Practical Application: An important goal for research institutions and the brewery industry is to produce colored malt by combining microwave and hot air roasting, while saving energy, getting desirable color, and avoiding the formation of carcinogenic and toxic neo-formed contaminants (NFCs). Therefore, one objective of this study was to compare energy consumption and content of NFCs during roasting of malt by hot air-only and combined microwave–hot air processes as well as to determine the effect of specific power, microwave processing time, oven temperature, and oven processing time during combined microwave–hot air roasting. Another objective was to predict the optimum conditions for the production of coffee, chocolate, and black malts.     

Psychological reactions during in-vitro fertilization: similar response pattern in husbands and wives

The purpose of this study was to examine differences in daily emotional, physical and social reactions among husbands and wives during in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Forty couples about to undergo ICSI or IVF at a private infertility clinic monitored their emotional, physical and social reactions daily for one complete treatment cycle from the first day of stimulation until the outcome of treatment was known (approximately 35 days). The results showed that men and women had a similar response pattern to oocyte retrieval, fertilization, embryo transfer and the pregnancy test. These stages were associated with the most significant changes in reactions for both spouses. The pattern of results suggested that the most important psychological determinant of reactions during IVF was the uncertainty of treatment procedures. Spouses appeared to be equally sensitive to this uncertainty and both appeared to respond to it with ambivalent feelings involving emotional distress and positive feelings of hope and intimacy.     

Influence of magnesium substitution on a collagen-apatite biomaterial on the production of a calcifying matrix by human osteoblasts

The induction of a calcifying matrix is of great interest in the restoration of bone defects. In a previous in vitro study we demonstrated that a collagen sponge constituted of type I collagen fibrils, chondroitin sulfates, and hydroxyapatite crystals induces an earlier and a more abundant synthesis of a new extracellular calcifying matrix than do other biomaterials such as collagen or hydroxyapatite alone. Bone mineral contains various amounts of magnesium ions, either adsorbed at the surface of apatite crystals or incorporated inside the crystal structure. Magnesium is known to reduce the degradation rate of tricalcium phosphate ceramics and to influence the crystallization of mineral substance. Thus we evaluated two sponges modified with different substituted apatites. The substituted low magnesium-containing apatite sample decreased the osteoinductive properties of the sponge whereas the substituted high magnesium-containing apatite sample had a toxic effect on bone cells and prevented the formation of any extracellular matrix. Such a toxic effect can be explained by the presence of large numbers of magnesium ions released into the culture medium even though at physiological level magnesium is able to promote bone mineralization and to control the growth of hydroxyapatite crystals. Thus collagen sponges containing hydroxyapatite remain one of the most appropriately evaluated biomaterials used for the restoration of periodontal pockets and bone defects.     

Cost effectiveness of screening for primary open angle glaucoma

OBJECTIVES AND SETTING: To determine the cost effectiveness of screening for glaucoma. METHODS: Information on treatment efficacy, diagnostic methods, epidemiological characteristics of glaucoma, and costs were determined from the literature, from administrative databases, and from experts. Scenarios with different screening frequency, age, participation in screening, compliance with treatment, treatment efficacy, and diagnostic tests were examined. RESULTS: The initial scenario comprised three-yearly screening of subjects aged 40-79 by funduscopy and tonometry, followed by perimetry when abnormalities were discovered. The assumption of levels of participation in screening and of compliance with treatment of 75%, and treatment efficacy of 50% resulted in a cost of $C100,000 per year of blindness prevented. A scenario in which screening was restricted to subjects aged 65-79, with the same input variables, would prevent 81% of the cases of blindness prevented with scenario 1, at a cost of $C42,000 per year of blindness prevented. Screening with tonometry only as the initial diagnostic test in subjects aged 65-79 would result in a cost of $C36,000 per year of blindness prevented, but would only prevent 59% of the cases prevented with scenario 1. CONCLUSIONS: There is as yet no proof that treatment of glaucoma or of high intraocular pressure will arrest the progression of glaucoma to blindness. Even when treatment efficacy is assumed to be as high as 50%, however, the cost effectiveness of most glaucoma screening programmes considered would not be competitive.     

High sensitivity and analyte capture with desorption/ionization mass spectrometry on silylated porous silicon

Silylation chemistry on porous silicon provides for ultrahigh sensitivity and analyte specificity with desorption/ionization on silicon mass spectrometry (DIOS-MS) analysis. Here, we report that the silylation of oxidized porous silicon offers a DIOS platform that is resistant to air oxidation and acid/base hydrolysis. Furthermore, surface modification with appropriate hydrophobic silanes allows analytes to absorb to the surface via hydrophobic interactions for direct analyte extraction from complex matrixes containing salts and other nonvolatile interferences present in the sample matrix. This enables rapid cleanup by simply spotting the sample onto the modified DIOS target and removing the liquid phase containing the interferences. This approach is demonstrated in the analysis of protein digests and metabolites in biofluids, as well as for the characterizing of inhibitors from their enzyme complex. An unprecedented detection limit of 480 molecules (800 ymol) for des-Arg(9)-bradykinin is reported on a pentafluorophenyl-functionalized DIOS chip.