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.     

Biowaste-derived hydroxyapatite reinforced with polyvinyl pyrrolidone/aloevera composite for biomedical applications

The present investigation focuses on the synthesis of crabshell-derived hydroxyapatite (CS-HAP)/ water-soluble synthetic polymer—polyvinylpyrrolidone(PVP)/aloevera(AV)—a natural biopolymer, as a composite for enhanced mechanical, antibacterial and biocompatible properties. The reinforcement of polymer has a significant function in increasing the mechanical property of the composite, whereas the incorporation of AV improves the antibacterial and biocompatibility. Phase composition, morphology, mechanical property, and hydrophilicity of CS-HAP/PVP/AV biocomposite with different concentrations of PVP and AV were examined by Fourier transform infrared spectroscopy (FTIR), X-Ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray (SEM-EDX), Vickers microhardness tests, contact angle, respectively. Furthermore, the antibacterial efficiency of the composite is assessed using Escherichia coli (E coli) and Staphylococcus aureus (S aureus). The biocompatibility of HOS MG 63 cells on the CS-HAP/PVP/AV composite is evaluated by MTT assay test. The obtained results evidence that the as-synthesized composite have appropriate mechanical, antibacterial and biocompatible properties. Overall, the combination of mechanical property of PVP, antibacterial and biocompatible property of AV in CS-HAP/PVP/AV, makes the composite a potential therapeutic material for various biomedical applications.     

Paf-acether in human skin

Paf is a phospholipid mediator present in human skin which induces inflammatory events such as neutrophil infiltration and increased vascular permeability. Recent data suggest that cutaneous cells, such as fibroblasts and keratinocytes, produce paf and that paf is released during allergic cutaneous reactions. It is tempting to speculate that paf may contribute to the development of various skin disorders with acute and chronic skin inflammation. Paf antagonists may help in bringing answers to this hypothesis and may offer new prospects for the treatment of cutaneous inflammatory diseases. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.     

Silphinene Sesquiterpenes as Model Insect Antifeedants

Silphinene sesquiterpenes are established chrysomelid antifeedants. In this work, nine silphinene analogs, 11-acetoxy-5-angeloyloxysilphinen-3-one (1), 11-acetoxy-5-tigloyloxysilphinen-3-one (2), 11-acetoxy-5-iso- butyryloxysilphinen-3-one (3), 11-hydroxy-5-angeloyloxysilphinen-3-one (4), 11,5-dihydroxysilphinen-3-one (5), 11,5-diacetoxysilphinen-3-one (6), 5,11-diisobutyryloxysilphinen-3-one (7), silphinen-3,5,11-trione (8), and O-methyl-5-epicantabrenolic acid methyl ester (10), and a presilphiperfolane sesquiterpene (9) were tested against several divergent insect species, including the lepidopteran Spodoptera littoralis, the chrysomelid Leptinotarsa decemlineata, and five aphid species, and their antifeedant effects were compared with those of picrotoxinin, a GABA-antagonist, and thymol, an allosteric modulator for insect GABA receptors. All insects tested responded to at least one silphinene analog and/or GABA antagonist. Compound 3 and thymol were effective antifeedants against all species tested except S. littoralis, with varying potencies according to their feeding ecologies. The toxicity of these compounds was species-dependent and did not correlate with their antifeedant effect.     

Optimization of an herbicide release from ethylcellulose microspheres

Summary The herbicide 2,4-D was microencapsulated using ethyl cellulose to develop controlled release formulations that protect it from photodegradation and evaporation and to reduce the environment pollution. Ethyl cellulose microspheres loaded with 2,4-D were prepared by the emulsion solvent-evaporation technique. We have obtained the desired microspheres with higher drug entrapment and encapsulation yield by varying certain conditions as stirring speed, polymer-solvent ratio, drug-polymer ratio, pH of continuous phase and organic phase solvent. The shape and size of microspheres were analysed by scanning electron microscopy. The herbicide release was studied at 25 °C and the release data were analysed according to Fick’s Law. The results demonstrate that we can control the release rate by modifying the process parameters.     

Complementarity determining region residues aspartic acid at H55, serine at H95 and tyrosines at H97 and L96 play important roles in the B72.3 antibody-TAG72 antigen interaction

Structural analysis derived from the crystallographic studyof the chimeric B72.3 antibody illustrated some major atomicinteractions between complementarity determining region (CDR)residues. For example, hydrogen bonds are formed between H35/H95,L50/H97, H53/H55 and H96/L96 respectively. These CDR residuesmay play important roles in the B72.3–TAG72 (antibody-antigen)interaction either by direct interaction with the TAG72 antigenor by maintaining a CDR loop conformation through atomic interactionsbetween CDR residues. In order to confirm these assumptions,we altered these CDR residues by site-directed mutagenesis anddetermined binding affinities of these mutant chimeric antibodiesfor the TAG72 antigen in a solid-phase radioimmunoassay. Wefound that H55, H95, H97 and L96 are important CDR residuesfor the B72.3–TAG72 interaction. Single amino acid substitutionsof aspartic acid and serine by alanine at H55 of CDR2 and atH95 of CDR3 respectively and of tyrosine by phenylalanine atH97 and L96 of CDR3, significantly reduced the binding affinityfor the TAG72 antigen by 20-, 8-, 16- and 45-fold respectively.Therefore, this study reveals some of the requirements for maintainingthe integrity of the B72.3 antibody combining sites.     

Modification of the porosity of pillared clays by carbon deposition. I. Polymer carbonization

In order to use pillared clays (PILC) for selective adsorption, further modifications of the porous structure are necessary. The deposition of carbon residues onto the porous structure of pillared clays by the carbonization of polymers (polyvinylalcohol) was proposed to achieve a controlled modification of the pore size. Ti and Al-pillared clays (calcined and non-calcined) were impregnated with PVA (different grades and different concentrations and subsequently carbonized to form carbon phases. The effect of the carbon deposits on the porosity of Ti- and Al-PILC is discussed in terms of pore-blocking, pore-filling and pore-narrowing. The deposition of carbon using PVA resulted in a complete pore-blocking for Al-PILC and in a narrowing of the pore size distribution for Ti-PILC, without achieving a controlled pore-narrowing.     

Epsilon Flock: a model migration language

Model-driven engineering introduces additional challenges for controlling and managing software evolution. Today, tools exist for generating model editors and for managing models with transformation, validation, merging and weaving. There is limited support, however, for model migration—a development activity in which instance models are updated in response to metamodel evolution. In this paper, we propose conservative copy—a style of model transformation that we believe is well-suited to model migration—and Epsilon Flock—a compact model-to-model transformation language tailored for model migration. The proposed structures are evaluated by comparing the conciseness of model migration strategies written in different styles of transformation language, using several examples of evolution taken from UML and the graphical modelling framework.     

Modification of industrial polypropylene film by grafting of poly(acrylic acid)

Grafting of poly(acrylic acid) onto commercial polypropylene films following irradiation by γ-rays was carried out in order to improve their surface properties. The amount of grafting with the irradiation dose was found not to follow the expected linear dependence as it is normally observed for polypropylene films prepared in laboratory amounts. We therefore analyzed the influence of the industrial manufacture process in terms of orientation of the film and addition of antioxidants by determining the peroxide surface density and the extent of grafting therefrom. The unoriented polypropylene film presented the highest peroxide concentration and was thus the most adapated material for successful grafting. Whereas phenol antioxidants limit the peroxide formation and thus must be removed from the film for grafting, the thickness of the chemical modification and can be controlled by means of phosphites. Atomicforce microscopy and wettability measurements showed that the grafted poly(acrylic acid) was heterogeneously distributed on the surface of the film, explaining the observed low reproducibility of the grafting reaction. However, we observed that the polarity of the surface was increased by the grafting. © 1995 John Wiley & Sons, Inc.