Efficient drug delivery to alveolar macrophages and lung epithelial lining fluid following pulmonary administration of liposomal ciprofloxacin in rats with pneumonia and estimation of its antibacterial effects

The efficacy of pulmonary administration of liposomal ciprofloxacin (CPFX) in pneumonia was evaluated. In brief, the pharmacokinetics following pulmonary administration of liposomal CPFX (particle size, 1,000 nm; dose, 200 microg/kg) were examined in rats with lipopolysaccharide-induced pneumonia as an experimental pneumonia model. Furthermore, the antibacterial effects of liposomal CPFX against the pneumonic causative organisms were estimated by pharmacokinetic/pharmacodynamic (PK/PD) analysis. The time-courses of the concentration of CPFX in alveolar macrophages (AMs) and lung epithelial lining fluid (ELF) following pulmonary administration of liposomal CPFX to rats with pneumonia were markedly higher than that following the administration of free CPFX (200 microg/kg). The time course of the concentrations of CPFX in plasma following pulmonary administration of liposomal CPFX was markedly lower than that in AMs and ELF. These results indicate that pulmonary administration of liposomal CPFX was more effective in delivering CPFX to AMs and ELF compared with free CPFX, and it avoids distribution of CPFX to the blood. According to PK/PD analysis, the liposomal CPFX exhibited potent antibacterial effects against the causative organisms of pneumonia. This study indicates that pulmonary administration of CPFX could be an effective technique for the treatment of pneumonia.     

Comparison of failure mechanisms between rubber-modified and unmodified epoxy adhesives under mode II loading condition

The effect of rubber modification on fracture toughness of adhesive joints under mode II loading condition was investigated in comparison with that under mode I loading, wherein the two adhesives rubber-modified and unmodified were used. To evaluate the fracture toughness on the basis of R-curve characteristics under mode II loading condition, four-point bend tests had been conducted for the adhesively bonded end-notched flexure (ENF) specimens. Thus obtained R-curves revealed the following trend: its behavior did not appear for the unmodified adhesive, whereas the rubber-modified adhesive exhibited a typical behavior. In the initial stage of crack propagation, G _IIC of the rubber-modified adhesive is lower than that of the unmodified adhesive, but becomes greater in the range of Δa > 25 mm. Nevertheless, the significant improvement of the fracture toughness with the rubber modification under mode I loading condition was not observed under mode II loading. Moreover, FEM analysis was made to elucidate the relation between the above fracture behavior and stress distributions near the crack tip. The results gave the reasonable relationship between evolution of plastic zone and the area with high void-fraction as well as the R-curves behavior. In addition, macroscopic and SEM observations for the fracture surfaces were also conducted.     

Tumor suppressive monoclonal antibody belonging to the V(H) 7183 family directed to the oncodevelopmental carbohydrate antigen on human hepatocellular carcinoma

Hep27 monoclonal antibody (Hep27 Mab) was raised by immunizing BALB/c mice with cells of the Thai human hepatocellular carcinoma (HCC) cell line HCC-S102 using hybridoma technology. The Hep27 Mab recognizes oncofetal development antigens by reacting with many HCC, other cancers, fetal and newborn liver but not adult liver. The Hep27 Mab alone markedly inhibits the growth of hepatocellular carcinoma cell lines (65% viability on the third day), suggesting its clinical usefulness. Moreover, complementary DNA (cDNA) for active variable regions of both heavy and light chains of the antibody has been cloned. Sequence analysis of the variable region of the Hep27 Mab revealed that the V(H) and V(L) genes belong to the V(H) 7183 and V(K) families, respectively. We have also characterized the reactivity of the Hep27 Mab to synthetic carbohydrate epitopes and 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP)-treated HCC-S102 cells. The results showed that the Hep27 Mab recognizes a neoglycolipid containing a mucin core unit and PDMP treatment reduced Hep27 Mab binding activity to HCC-S102 cells, indicating that the Hep27 Mab recognizes a glycolipid antigen on HCC-S102 cells. This Mab may be potentially useful for studying antigenic expression in hepatocellular carcinoma and as a targeting agent for radioimmunodetection and immunoconjugated therapy.     

Characterization of FtsZ homolog from hyperthermophilic archaeon Pyrococcus kodakaraensis KOD1

The gene of bacterial type ftsZ homolog in hyperthermophilic archaeon, Pyrococcus kodakaraensis KOD1 (Pk-ftsZ), was identified. The gene product of the Pk-ftsZ gene is composed of 380 amino acids with a molecular mass of 41,354 Da. In the deduced amino acid sequence of the Pk-ftsZ gene, a glycine-rich sequence (Gly-Gly-Gly-Thr-Gly-Ala-Gly) implicated in GTP binding was well conserved. The Pk-ftsZ gene was overexpressed using Escherichia coli as a host and the recombinant protein was purified. The purified Pk-FtsZ protein exhibited GTPase activity with optimum temperatures higher than 80 degrees C. However, the protein showed little GTPase activity at 40 degrees C, indicating that a high reaction temperature is required for the GTPase activity in accordance with the thermophilic nature of P. kodakaraensis KOD1. The GTP-binding ability of Pk-FtsZ protein could also be detected by UV-induced cross-linking of a protein to [alpha-32P] GTP. The Pk-ftsZ gene was expressed in E. coli cells with a temperature-sensitive ftsZ mutation, E. coli ftsZ84 (ts), but its mutant phenotype of elongated cell form at a nonpermissive temperature (42 degrees C) could not be compensated, possibly because of the thermophilic nature of the Pk-FtsZ. Pk-FtsZ could form protofilaments in a GTP-dependent manner at 90 degrees C. Results of phylogenetic analysis suggest that there might be additional factors required for formation of the Z ring in P. kodakaraensis KOD1.     

Standard infrared absorption spectrum of betaine and optimal conditions for its measurement

The infrared absorption (IR) spectrum is often used as a standard reference in identification tests of food additives in Japan. In the case of betaine, many different IR spectra have been reported and, therefore, it is necessary to establish an IR spectrum that is reproducible and reliable enough to be used as a standard for identification. In the present study, suitable conditions to obtain a standard IR spectrum were examined from various viewpoints, including pretreatment, selection of method, and measuring technique. The KBr disk method, which has generally been used to identify betaine, was found to be humidity-dependent, and there was also an interaction between betaine and KBr. A reproducible IR spectrum suitable as a standard could be obtained by drying betaine at 105 degrees C for 3 hours over phosphorus pentoxide, and then measuring the IR spectrum by the liquid paraffin (Nujol) paste method.     

Co2+-Substitution Effect in Ce-TZP/La M-type Hexaferrite Composites

A Ce-TZP/platelike La(Co(Fe_0.9Al_0.1)₁₁)O₁₉ composite was synthesized in situ while sintering from a mixture of Ce-TZP, La(Fe_0.9Al_0.1)O₃, Fe₂O₃, Al₂O₃, and CoO powders. Platelike La(Co(Fe_0.9Al_0.1)₁₁)O₁₉ crystals were grown in a dense Ce-TZP matrix after sintering at temperatures of 1200°–1350°C. The temperature range for sintering Ce-TZP/La(Fe,Al)₁₂O₁₉ composites was expanded widely by substituting Co²⁺ ions for Fe²⁺ ions in its structure. The highest value of the bending strength of the Ce-TZP/La(Co(Fe_0.9Al_0.1)₁₁)O₁₉ composites was 880 MPa, which was higher than that of the Ce-TZP/La(Fe,Al)₁₂O₁₉ composite (780 MPa) and Ce-TZP (513 MPa). The saturation magnetization of the Ce-TZP/La(Co(Fe_0.9Al_0.1)₁₁)O₁₉ composite was a constant value of 7.7 emu/g after the composite was sintered at 1200°–1350°C.     

Electroless coating of Fe3Si on steel in the molten salt

The corrosion‐resistive intermetallic compound Fe₃Si could non‐electrolytically coat pure iron and mild steel. The disproportional reaction between Si and Si⁴⁺ ions deposited the homogeneous Fe₃Si layer on the Fe substrates, by using solid silicon and the molten salt composed of NaCl‐KCl‐NaF‐Na₂SiF6‐SiO₂. SiF₄ gas evaporation prevented from continuous siliconization, when only Na₂SiF₆ was used as Si⁴⁺ ion source. By adding SiO₂ into the salt as another source, the molten salt became endurable for repeated usage in air. The layer of Fe₃Si single phase with silicon mole fractions of 24 ± 1 % grew thicker than 200 μm by immersing for a few hours at 973 – 1173K.     

Fracture and yield behavior of adhesively bonded joints under triaxial stress conditions

Most of adhesively bonded joints are under complicatedly distributed triaxial stress in the adhesive layer. For the estimating of the strength of adhesively bonded joints, it is crucial to clarify behavior of yield and failure of the adhesives layer under triaxial stress conditions. Two types of the adhesively bonded joints were used in this study: One is the scarf joint which is under considerably uniform normal and shear stresses in the adhesive layer, where their combination ratio can be varied with scarf angle. The other is the butt joint with thin wall tube in which considerably uniform pure shear can be realized in the adhesive layer under torsional load conditions. These joints can cover the stress triaxiality in adhesive layers of most joints in industrial application. The effect of stress triaxiality on the yield and fracture stresses in the adhesive layer were investigated using the joints bonded by three kinds of adhesives in heterogeneous and homogeneous systems. The results showed that both the yield and failure criterion depend on the stress triaxiality and that the fracture mechanism of the homogeneous adhesive is different from that of the heterogeneous one. From these experimental results, a method of estimating the yield and failure stresses was proposed in terms of a stress triaxiality parameter.     

Estimation of Fatigue Strength for Adhesively-Bonded Lap Joints Based on Fatigue Failure Criterion Under Multiaxial Stress Conditions

A method for estimation of endurance limits for adhesively-bonded single and single-step double-lap joints was proposed which considers the stress multiaxiality in the adhesive layer. At first, fatigue tests and finite element analysis were conducted for these lap joints. Then, endurance limits of these joints were estimated using their stress distributions and critical regression equations which were obtained from the S-N data of adhesively-bonded scarf- and butterfly-type joints. The results indicate that the endurance limits of these lap joints can be estimated from the regression equation based on the maximum principal stress.