Improved oxidation stability and crosslink density of chemically crosslinked ultrahigh molecular weight polyethylene using the antioxidant synergy for artificial joints.

Vitamin E (VE) is currently an approved antioxidant to improve the oxidation stability of highly crosslinked ultrahigh molecular weight polyethylene (UHMWPE) insert used commercially in total joint arthroplasty. However, the decrease in crosslink density caused by VE reduces wear resistance of UHMWPE, showing an uncoordinated challenge. In this work, we hypothesized that D-sorbitol (DS) as a secondary antioxidant can improve the antioxidant efficacy of VE on chemically crosslinked UHMWPE. The combined effect of VE and DS on oxidation stability of UHMWPE was investigated at a set of controlled hybrid antioxidant content. The hybrid antioxidant strategy showed significantly synergistic enhancement on the oxidation stability of chemically crosslinked UHMWPE compared with the single VE strategy. More strikingly, the crosslink density of the blends with hybrid antioxidants stayed at a high level since DS is not sensitive to crosslinking. The relationships between oxidation stability, mechanical properties, crosslink density, and crystallinity were investigated, by which the clinically relevant overall performance of UHMWPE was optimized. This work provides a leading-edge design mean for the development of joint bearings.

Nanoparticle-target interactions parallel antibody-protein interactions.

Magnetic particles can act as magnetic relaxation switches (MRSw's) when they bind to target analytes, and switch between their dispersed and aggregated states resulting in changes in the spin-spin relaxation time (T(2)) of their surrounding water protons. Both nanoparticles (NPs, 10-100 nm) and micrometer-sized particles (MPs) have been employed as MRSw's, to sense drugs, metabolites, oligonucleotides, proteins, bacteria, and mammalian cells. To better understand how NPs or MPs interact with targets, we employed as a molecular recognition system the reaction between the Tag peptide of the influenza virus hemagglutinin and a monoclonal antibody to that peptide (anti-Tag). To obtain targets of different size and valency, we attached the Tag peptide to BSA (M(w)= 65000 Daltons, diameter = 8 nm) and to Latex spheres (diameter = 900 nm). To obtain magnetic probes of very different sizes, anti-Tag was conjugated to 40 nm NPs and 1 microm MPs. MP and NP probes reacted with Tag peptide targets in a manner similar to antibody/antigen reactions in solution, exhibiting so-called Prozone effects. MPs detected all types of targets with higher sensitivity than NPs with targets of higher valency being better detected than those of lower valency. The Tag/anti Tag recognition system can be used to synthesize combinations of molecular targets and magnetic probes, to more fully understand the aggregation reaction that occurs when probes bind targets in solution and the ensuing changes in water relaxation times that result.

Modulation of enzyme-substrate selectivity using tetraethylene glycol functionalized gold nanoparticles.

Tetraethylene glycol (TEG) functionalized gold nanoparticles with 2 nm core diameters (AuTEG) enhance alpha-chymotrypsin (ChT) enzyme activity in a substrate-selective fashion. We explored the hydrolysis of four different substrates and observed a marked increase in activity with the most hydrophobic substrate N-succinyl-alanine-alanine-proline-phenylalanine- p-nitroanilide (TP), while the other substrates remain virtually unaffected by the AuTEG 'crowding effect' in solution. The enhancement in catalysis is indicated by an increase in K(cat)/K(m) as obtained from Lineweaver-Burk analysis and we hypothesize it to arise from a macromolecular crowding effect analogous to that observed with high molecular weight poly(ethylene glycol) (PEG) polymers.

IgG4-related sialadenitis complicated with type III mixed cryoglobulinemia: A case report.

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases. PATIENT CONCERNS: A 55-year-old female was admitted because of dry mouth and teeth falling off. DIAGNOSES: The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4 plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine. INTERVENTIONS AND OUTCOMES: After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS. LESSONS: Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.

Preparation of pH-responsive stationary phase for reversed-phase liquid chromatography and hydrophilic interaction chromatography.

Novel pH-responsive polymer-grafted silica was successfully synthesized through the radical "grafting from" polymerization on azo initiator-immobilized silica. The immobilization of azo initiator onto the silica surface was achieved by the reaction of surface amino groups with 4,4'-azobis(4-cyanovaleric acid chloride). The polymer-grafted silica was prepared by stirring suspension of the azo initiator-immobilized silica in anhydrous dioxane containing acrylic acid (AAc) and butyl acrylate (BA). The resulting polymer-grafted silica was demonstrated to be pH responsive to hydrophobic/hydrophilic property by reversed-phase liquid chromatography (RPLC) and hydrophilic interaction chromatography (HILIC). In RPLC mode, the retention of aromatic compounds decreased with the increase in the pH of mobile phase. However, the opposite result was obtained in HILIC mode; the retention of soybean isoflavones was stronger with the mobile phase at higher pH. Finally, the separations of sulfonamides and soybean isoflavones were carried out in RPLC mode and the separation of some nucleotides was achieved in HILIC mode.

In situ observation of place exchange reactions of gold nanoparticles. Correlation of monolayer structure and stability.

Place exchange reactions were studied using dye displacement: subtle changes in ligand structure greatly affected both the rate of displacement and the stability of the monolayer.

[Effect of intranasal IL-12 gene therapy on the mice eosinophils and IL-5 in the murine model of allergic rhinitis].

OBJECTIVE: To evaluate the effect of intranasal liposome-mediated IL-12 gene therapy on the eosinophils and IL-5 in the murine model of allergic rhinitis. METHODS: Thirty-six BALB/C mice were randomly divided into allergic rhinitis (AR) group, gene therapy group and control group. Allergic rhinitis group were sensitized and stimulated by ovalbumin (OVA), and gene therapy group were administered with liposome-mediated pGEG. mIL-12 transnasally before stimulated. The eosinophils in bone marrow were counted by Wright's staining, and the eosinophils in nasal mucosa were counted by HE staining. The eosinophils of peripheral blood were detected by flow cytometry. The expression of IL-5 in bone marrow and nasal mucosa was examined by immunohistochemistry. The IL-5 in serum was detected by ELISA. RESULTS: Among the three groups, the difference of all data was statistically significant (P<0.01). Multiple Comparison showed that the ratio of eosinophils to white cells and the mount of IL-5 positive cells in nasal mucosa and bone marrow of gene therapy group was significantly lower than that of AR group (P<0.05). The ratio of eosinophils to granulocyte (0.124 +/- 0.031) and the expression level of IL-5 [(29.51 +/- 6.68) pg/ml] in peripheral blood [ 0.184 +/- 0.079 and (56.58 +/- 16.80) pg/ml] were significantly lower in gene therapy group than in AR group (P<0.05). CONCLUSIONS: Transnasal administration of liposome- mediated pGEG. mIL-12 could depress the expression of IL-5 in bone marrow, peripheral blood, and nasal mucosa, to influence the proliferation and differentiation of eosinophils and decrease the delivery and transference of eosinophils to peripheral blood and nasal mucosa. It may be a new treatment for respiratory tract allergic inflammation.

Ordered CdSe nanoparticles within self-assembled block copolymer domains on surfaces.

Hierarchical, high-density, ordered patterns were fabricated on Si substrates by self-assembly of CdSe nanoparticles within approximately 20-nm-thick diblock copolymer films in a controlled manner. Surface-modified CdSe nanoparticles formed well-defined structures within microphase-separated polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) domains. Trioctylphosphine oxide (TOPO)-coated CdSe nanoparticles were incorporated into PS domains and polyethylene glycol-coated CdSe nanoparticles were located primarily in the P2VP domains. Nearly close-packed CdSe nanoparticles were clearly identified within the highly ordered patterns on Si substrates by scanning electron microscopy (SEM). Contact angle measurements together with SEM results indicate that TOPO-CdSe nanoparticles were partially placed at the air/copolymer interface.

Recognition-directed orthogonal self-assembly of polymers and nanoparticles on patterned surfaces.

We demonstrate the patterning of silica substrates with thymine (Thy-PS) and positively charged N-methylpyridinium (PVMP) polymers using photolithography and the subsequent orthogonal modification of these surfaces using diaminopyridine-functionalized polystyrene (DAP-PS) and carboxylate-derivatized CdSe/ZnS core-shell nanoparticles (COO-NP) through diamidopyridine-thymine three-point hydrogen bonding and pyridinium-carboxylate electrostatic interactions, respectively. This two-component orthogonal surface modification was accomplished in a self-sorting, single-step fashion, providing a versatile tool for the rapid and efficient creation of complex materials.

Noncovalent modification of chymotrypsin surface using an amphiphilic polymer scaffold: implications in modulating protein function.

We report here on a new amphiphilic homopolymer that binds noncovalently to proteins. This polymer not only binds to the target protein chymotrypsin with submicromolar affinity but also stabilizes the native structure of the protein. Since the polymer-protein binding process is based on electrostatic interaction, the bound protein can be released from the polymer surface and reactivated either by increasing the ionic strength or by adding complementary cationic surfactants. The electrostatic binding of polymer to the protein results in a marked change in the substrate specificity of chymotrypsin.

Control of protein structure and function through surface recognition by tailored nanoparticle scaffolds.

Thioalkyl and thioalkylated oligo(ethylene glycol) (OEG) ligands with chain-end functionality were used to fabricate water-soluble CdSe nanoparticle scaffolds. Surface recognition of chymotrypsin (ChT) was achieved using these functionalized nanoparticle scaffolds, with three levels of interaction demonstrated: no interaction (OEG terminated with hydroxyl group), inhibition with denaturation (carboxylate-terminated thioalkyl ligands), and inhibition with retention of structure (carboxylate-terminated OEG). The latter process was reversible upon an increase in ionic strength, with essentially complete restoration of enzymatic activity.