Aggregated eosinophils and neutrophils characterize the properties of mucus in chronic rhinosinusitis.

BACKGROUND: Airway obstruction caused by viscous mucus is an important pathophysiologic characteristic of persistent inflammation, which can result in organ damage. OBJECTIVE: We investigated the hypothesis that the biophysical characteristics of accumulating granulocytes affect the clinical properties of mucus. METHODS: Surgically acquired nasal mucus samples from patients with eosinophilic chronic rhinosinusitis and neutrophil-dominant, noneosinophilic chronic rhinosinusitis were evaluated in terms of computed tomography density, viscosity, water content, wettability, and protein composition. Isolated human eosinophils and neutrophils were stimulated to induce the formation of extracellular traps, followed by the formation of aggregates. The biophysical properties of the aggregated cells were also examined. RESULTS: Mucus from patients with eosinophilic chronic rhinosinusitis had significantly higher computed tomography density, viscosity, dry weight, and hydrophobicity compared to mucus from patients with noneosinophilic chronic rhinosinusitis. The levels of eosinophil-specific proteins in mucus correlated with its physical properties. Eosinophil and neutrophil aggregates showed physical and pathologic characteristics resembling those of mucus. Cotreatment with deoxyribonuclease and heparin, which slenderizes the structure of eosinophil extracellular traps, efficiently induced reductions in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. CONCLUSIONS: The present study elucidated the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a novel perspective. These findings may contribute to the development of treatment strategies for eosinophilic airway diseases.

Synthesis and Antiplatelet Adhesion Behavior of a Poly(L-lactide-co-glycolide)-Poly(1,5-dioxepan-2-one) Multiblock Copolymer.

Platelet adhesion and denaturation on artificial medical implants induce thrombus formation. In this study, bioabsorbable copolymers composed of poly(l-lactide-co-glycolide) (PLGA) and poly(1,5-dioxepan-2-one) (PDXO) were synthesized and evaluated for their antiplatelet adhesive properties. The PLGA-PXO multiblock copolymer (PLGA-PDXO MBC) and its random copolymer (PLGA-PDXO RC) showed effective antiplatelet adhesive properties, and the number of adhered platelets was similar to those adhered on poly(2-methoxyethylacrylate), a known antiplatelet adhesive polymer, although a large number of denatured platelets were observed on a PLGA-poly(ε-caprolactone) multiblock copolymer (PLGA-PCL MBC). Using monoclonal antifibrinogen IgG antibodies, we also found that both αC and γ-chains, the binding sites of fibrinogen for platelets, were less exposed on the PLGA-PDXO MBC surface compared to PLGA-PCL MBC. Furthermore, free-standing films of PLGA-PDXO MBC were prepared by casting the polymer solution on glass plates and showed good tensile properties and slow hydrolytic degradation in phosphate-buffered saline (pH = 7.4). We expect that the unique properties of PLGA-PDXO MBC, i.e., antiplatelet adhesive behavior, good tensile strength, and hydrolytic degradation, will pave the way for the development of new bioabsorbable implanting materials suitable for application at blood-contacting sites.

Highly Selective Rh(III) Recovery from HCl Solutions Using Aromatic Primary Diamines via Formation of Three-Dimensional Ionic Crystals.

A new Rh(III) separation method using metal-containing hydrochloric acid (HCl) solutions has been developed. This method includes Rh(III) precipitation with high selectivity using aromatic primary diamines as precipitants. The compound p-phenylene diamine dihydrochloride (PPDA) successfully precipitates only Rh(III) from HCl solutions containing Pd(II), Pt(IV), and Rh(III). Furthermore, highly selective Rh(III) recovery from the simulated spent catalyst leach solution, comprising Pd, Pt, Rh, Ce, Al, Ba, Zr, La, and Y in 5 M HCl, was achieved using PPDA. Single-crystal X-ray analysis revealed that the Rh(III)-containing precipitate using PPDA forms three-dimensional ionic crystals comprising the [RhCl6]3-/ammonium form of PPDA/chloride anion/H2O at a 1:2:1:2 ratio. Formation of these unique ionic crystals plays a key role in the highly selective Rh(III) recovery. This Rh(III) recovery method will be promising for use in the purification process of Rh as well as the practical Rh recovery from spent catalysts.

Preferential Precipitation and Selective Separation of Rh(III) from Pd(II) and Pt(IV) Using 4-Alkylanilines as Precipitants.

Rhodium (Rh) is the most expensive platinum group metal (PGM) and is of great industrial importance. Although the recycling of PGMs from secondary sources is in high demand, the preferential and selective separation of Rh from PGM mixtures remains a great challenge. Here, a selective Rh separation method involving the precipitation of Rh from an HCl solution containing palladium (Pd), platinum (Pt), and Rh is reported. 4-Butylaniline and 4-hexylaniline were used as precipitants for Rh, and selective Rh precipitation was achieved at high HCl concentrations. We revealed that Rh in HCl selectively forms a unique and highly stable ion-pair complex comprising [RhCl6]3-/anilinium/chloride ions in a 1:6:3 ratio. The formation and high stability of the Rh complex were found to play important roles in the selective recovery of Rh from PGM mixtures.

Selective and Preferential Separation of Rhodium (III) from Palladium (II) and Platinum (IV) Using a m-Phenylene Diamine-Containing Precipitant.

Although Rh is an industrially important and the most expensive platinum group metal (PGM), the selective and preferential separation of Rh from PGM mixtures still remains as a big challenge. In this work, the separation of Rh (III) from Pd (II) and Pt (IV) in a hydrochloric acid (HCl) solution was studied using a m-phenylene diamine-containing precipitant (m-PDA). At high HCl concentrations (6.0-8.0 M), most of the Rh (III) (>90%) was precipitated, and Pd (II) and Pt (IV) were hardly precipitated (<5%). On the other hand, over 85% of Pd (II) and Pt (IV) precipitated along with small amount of Rh (III) (<25%) at low HCl concentrations (1.0-2.0 M). As a consequence, m-PDA enabled selective and preferential precipitation of Rh (III) at high HCl concentrations. XPS and TG analyses revealed that the Rh-containing precipitate is an ion-pair complex composed of one [RhCl6]3- anion and three m-PDA cations. The Rh desorption from the precipitate as well as the recovery of m-PDA was successfully achieved using an NH4OH solution. This method is a promising practical approach to Rh recovery.

73-kDa molecular chaperone HSP73 is a direct target of antibiotic gentamicin.

Although gentamicin (GM) has been used widely as an antibiotic, the specific binding protein of the drug has not yet been understood sufficiently. Here we show that GM specifically associates with the 73-kDa molecular chaperone HSP73 and reduces its chaperone activity in vitro. In the present study, we investigated GM-specific binding proteins using a GM-affinity column and porcine kidney cytosol. After washing the column, only the 73-kDa protein was eluted from the column by the addition of 10 mm GM. None of the other proteins were found in the eluant. Upon immunoblotting, the protein was identical to HSP73. Upon CD spectrum analysis, the binding of GM to HSP73 resulted in a conformational change in the protein. Although HSP73 prevents aggregation of unfolded rhodanese in vitro, the chaperone activity of HSP73 was suppressed in the presence of GM. Using limited proteolysis of HSP73 by TPCK-trypsin, the GM binding site is a COOH-terminal for one third of the protein known to be a peptide-binding domain. During immunohistochemistry, HSP73 and GM were co-localized in enlarged lysosomes of rat kidneys with GM-induced acute tubular injury in vivo. Our results suggest that the specific association between HSP73 and GM may reduce the chaperone activity of HSP73 in vitro and/or in vivo, and this may have an interaction with GM toxicity in kidneys with GM-induced acute tubular injury.